San Francisco PFS - Saturday Slide Deck

2024 San Francisco Patient and Family Seminar

April 12 & 13, 2024

MANY THANKS TO OUR SPONSORS!

What do the dots mean?

More than 1 year since diagnosis

Stem cell transplant recipient

Less than 1 year diagnosed

Care Partner for someone with Myeloma

Saturday Agenda: Morning

7:00 – 8:00 AM Registration & Breakfast

8:00 – 8:10 AM Welcome & Announcements

Yelak Biru & Robin Tuohy

8:10 – 8:30 AM President & CEO Address

Yelak Biru, 28-year Myeloma Survivor Patient

8:30 – 9:15 AM Keynote Lecture: What is the Future of

Myeloma? w/ Q&A

Ajai Chari, MD, University of California - San Francisco

9:15 – 9:30 AM IMF Update: InfoLine

Teresa Miceli, RN, BSN, OCN

9:30 – 9:45 AM BREAK

Reminder: After Break, return to designated Break-Out Room

9:45 – 10:45 AM Breakout Sessions #1: Treatment Approaches in Myeloma

Breakout A: Newly Diagnosed: An Approach to Frontline Therapy

Caitlin Costello, MD; University of California - San Diego;

Teresa Miceli, Facilitator

Ballroom D: Drake

Breakout B: An Approach to Relapsed Myeloma

Amrita Krishnan, MD, FACP, City of Hope - Beckman, Duarte, CA

Robin Tuohy, Facilitator

Main Ballroom: B/C

10:45 – 10:50 AM RETURN TO MAIN SESSION

10:50 – 11:05 AM Partnering with the IMF

Sylvia Dsouza – Vice President, Development

11:05 – 11:40 AM Symptom Management and Living Well with Myeloma

Deborah Doss, RN, OCN, Dana-Farber Cancer Institute, Boston, MA

Nurse Leadership Board Member

11:40 AM – 12:00 PM Health Disparities in Myeloma, Joseph Mikhael, MD, MEd, FRCPC, FACP

Saturday Agenda: Afternoon

12:00 – 1:00 PM LUNCH

Reminder: After Lunch, return to designated Break-Out Room

1:00 – 1:40 PM Breakout Sessions #2:

Patients and Care Partners

1:40 – 1:45 PM RETURN TO GENERAL SESSION

1:45 – 2:15 PM Wild Card Topic: Practical Aspects of Immunotherapy

Ajai Chari, MD; University of California San Francisco

2:15 – 2:55 PM Ask – the – Experts with Guest Faculty

Breakout A: Patients Only – Lessons Learned

Facilitators: Michael Tuohy - 24-year Myeloma Survivor & Patient Advocate,

Support Group Leader

Yelak Biru, 28-year Myeloma Survivor Patient

Main Ballroom: B/C

2:55 – 3:00 PM Closing Remarks & Program Evaluation

Breakout B: Care Partners Only

Facilitators: Robin Tuohy & Teresa Miceli

Ballroom D: Drake

The IMF Support Group Team is Here For You!

Shared Experiences Help to Better Understand the Myeloma Journey

• Support Groups Empower Patients & Care Partners with information, insight, & hope

• The IMF provides educational support to a network of over 150 myeloma specific groups

We are happy to help connect you with an existing support group or help form a new one!

We assist with virtual, in-person, and hybrid options for meetings.

Local Support Groups: You Are Not Alone!

 Myeloma Stompers

(Napa/Sonoma)

Meets virtually the 2nd Friday of each month at 10AM

 San Gabriel Valley

Myeloma Support Group

Meets in-person the 1st Monday of each month at 6:30PM

 Upland, CA

Myeloma Support Group

Meets hybrid the 1st Friday of each month at 10AM

 San Francisco Bay Area

Myeloma Support Group

Meets virtually the 3rd Saturday of each month at 10AM

 Westlake Myeloma Support Group

Meets virtually the 2nd Saturday of each month at 11AM

 San Fernando Valley Myeloma Support Group

Meets in-person the 3rd Wednesday of each month at 7PM

 Sacramento Area

Myeloma Support Group

Meets virtually the 1st Saturday of each month at 10AM

Local Support Groups: You Are Not Alone!

 San Diego Multiple Myeloma Support Group

Meets hybrid the 2nd Monday of each month at 6:30PM

 Inland Empire, CA

Myeloma Support Group

Meets hybrid the 3rd Saturday of each month at 10:30AM

 Orange County

Myeloma Support Group

Meets in-person every other month & virtually the alternate months on the 1st Thursday of each month

 Los Angeles Multiple

Myeloma Support Group

Meets virtually on the 3rd Saturday of each month at 10:30AM

 Santa Cruz Multiple Myeloma Support Group

Meets virtually the 1st Monday of each month at 4:30PM

 Rancho Mirage, CA

Myeloma Support Group

Meets virtually on the 1st Thursday of each month at 3PM

Special Interest Virtual Groups

Special interest groups are designed as a supplemental support for specific populations of patients, in addition to their local Support Groups

 Las Voces de Mieloma Spanish speaking

patients & care partners

 Living Solo & Strong with Myeloma

For patients without a care partner

 High Risk Multiple Myeloma

For high-risk myeloma

Patients & care partners

Coming Soon!

 Care Partners Only

Designed to address the needs of care partners only

 Smolder Bolder

Created for people living with Smoldering Myeloma

 MGUS 4 Us

Created for people living with MGUS

 MM Families

For patients & care partners with young children

EVALUATION

Please be sure to complete your program evaluation today.

Questions 1 – 5 can be completed before the program begins.

Questions 7 & 8 can be answered after each presentation.

If you are attending Friday program only, we ask that you turn the survey in at the end of the day.

If you are coming back for the Saturday sessions, please hold onto your survey, bring it back tomorrow and turn it in at the end of the program.

We greatly appreciate your time and feedback!

President & CEO Address

28-year Myeloma Survivor Patient International Myeloma Foundation

Yelak Biru

EVALUATION

Please take a moment to reflect and respond to the program evaluation.

Questions 7 & 8 can be worked on after each presentation.

We greatly appreciate your time and feedback!

What is the Future of Myeloma?

Ajai Chari, MD

University of California San Francisco

What is the Future of Multiple Myeloma?

Ajai Chari, MD

Professor of Clinical Medicine

Director of Multiple Myeloma Program

Co-Director of Clinical Research, Hematology Oncology

University of California, San Francisco

What is the Future of Multiple Myeloma?

1. Smoldering Multiple Myeloma- To Treat Early/Cure or Not To Treat?

2. Will bone marrows ever go away?

3. Current unmet needs in MM requiring further effort

4. Moving Current Therapies Earlier/Novel Therapeutics

5. Treatment Free Intervals/Cure

SLiM-CRAB criteria

Comparison of the Predictive Value of FLCR ≥ 100 in Various Studies

So, is the risk of over treating SMM 2% or 54%?

1. Larsen JT et al. Leukemia 2013;27:941-6. 2. Kastritis E et al. Leukemia 2013;27:947-53. 5. Wu et al. Blood Advances 2018.

Newport Beach on a hot day on Saturday, April 25, 2020 during COVID pandemic.

(Telephoto lens Photo by Mindy Schauer, Orange County Register/SCNG)

Still of aerial video from helicopter (KTLA news)

Can we not do better than photographs (binary cutoffs eg FLCr >100, BM PC > 60%) in MM? Are there any movies?

Photograph vs Movie: A one time FLCr >100 is less predictive of SMM progression than evolving FLCr

Similar finding that increasing m protein, decreasing Hg were most predictive

MGUS-like (n=43)

Role of Biology: Not all SMM is Equal

Spanish series, untreated (N = 246)

Intermediate-like (n=168)

MM-like (n=35)

Early SMM Treatment vs Symptomatic TreatmentConsiderations for Future Therapeutic Studies

Clinical - Deep responses in SMM possible now

- Prevention/reduction of end-organ damage and infections

- Potential for increased OS and ? cure

Pathophysiology

Risk stratification

- Potential for increased curability due to presence of less genomic complexity

- Ability to target significant mutations

- Truly high-risk SMM very high probability of early progression

- Kinetic risk stratification may mitigate some biases

Trial design

- Randomized same regimen ethical & feasible

- Stratify by time from diagnosis

- Standardized sensitive osseous screening (WBLDCT, PET-CT, or MRI)

- Fix duration of treatment

Economic - Less end-organ damage costs

- Potential for increased OS - ? Cure

Treatment @ Symptoms

- Insufficient data re improved OS and PFS

- Treatment toxicity- Grade 3 /4 or chronic Grade

- Driver mutations have yet to be identified

Lack of global concordance, consensus regarding

Need  to incorporate additional phenotypic and

CURE

- MRD Negativity is not cure; relapses in GEM-

- Inability to specifically target biology – immune

- Lead & length time biases make benefits difficult to discern

- Likely prolonged therapy if not fixed duration

- Need for stem cell harvest if IMIDs used

What is the Future of Multiple Myeloma?

1. Smoldering Multiple Myeloma- To Treat Early/Cure or Not To Treat?

2. Will bone marrows ever go away?

3. Current unmet needs in MM requiring further effort

4. Moving Current Therapies Earlier/Novel Therapeutics

5. Treatment Free Intervals/Cure

Reasons for which bone marrow will likely NOT be going away soon

 Initial marrow to determine MGUS vs MM vs other conditions eg MDS

 In patients with persistently low blood counts out of proportion to disease or therapy – rule out bone marrow failure/leukemias

 To determine health of the bone marrow microenvironment - ? Cure

 If patients are truly nonsecretory by all available methods of monitoring

What about bone marrow for measureable residual disease (MRD)

But MRD negativity in the bone marrow is just one tool

 not as important if disease persists in blood, urine, or imaging

 MRD negativity must be sustained over time so repeated testing essential

} Need blood based MRD testing!

 prognostic value also depends on treatment used – chemo vs bispecifics vs transplant vs CART

 prognostic value depends on patient eg history of MGUS/SMM,  high risk, extramedullary

Paiva et al., Blood, 2015

Detection of MM proteins in BLOOD with very sensitive mass spectroscopy

% of bone marrow biopsies that could be avoided

What is the Future of Multiple Myeloma?

1. Smoldering Multiple Myeloma- To Treat Early/Cure or Not To Treat?

2. Will bone marrows ever go away?

3. Current unmet needs in MM requiring further effort

4. Moving Current Therapies Earlier/Novel Therapeutics

5. Treatment Free Intervals/Cure

Patients enrolled in real-world studies are often deemed ineligible for inclusion in randomized controlled trials

Registry/observational study patients ineligible for RCTs

German TLN

Connect MM

Optum’s EHR database

*Key RCT exclusion criteria included: ANC ≤1.5 × 109/L, platelet count ≤75 × 109/L, creatinine >2.5 mg/dL, AST/ALT >3 × ULN, peripheral neuropathy Grade >2; ECOG PS 3/4; history of MDS/other hematologic malignancies, or solid tumors 4 ALT, alanine aminotransferase; ANC, absolute neutrophil count; AST, alanine aminotransferase; d, dexamethasone; ECOG PS, European Cooperative Oncology Group performance status; EHR, electronic health record; HIV, human immunodeficiency virus; MDS, myelodysplastic syndromes; MM, multiple myeloma; NDMM, newly diagnosed multiple myeloma; RCT, randomized controlled trial; R, lenalidomide; TLN, Tumor Registry Lymphatic Neoplasms; ULN, upper limit of normal; V, bortezomib

1. Malecek M-K, et al. Clin Lymphoma Myeloma Leuk 2018;18:e363–4;

2. Knauf W, et al. Ann Hematol 2018;97:2437–45;

3. Hungria VTM, et al. ASH 2019 [poster #1887];

4. Wagner LI, et al. Blood 2019;134(Suppl 1): Abstract 1843;

5. Shah JJ, et al. Clin Lymphoma Myeloma Leuk 2017;17:575–83;

6. Chari A, et al. Clin Lymphoma Myeloma Leuk 2020;20:8–17.e16

Unadjusted, indirect comparison for illustration only; clinical significance is not implied. Cross-trial comparisons are potentially confounded by differences in trial design and study population.

Poorer outcomes in RCT-ineligible vs eligible patients in real-world data from registry studies

Study/registry N

Outcomes of ineligible vs eligible patients

1265 Rd treatment: 3-year OS: 63.5% vs 74.7% (mortality HR 1.46, 95% CI 1.03–2.07,

EHR database (Chari, et al)

INSIGHT MM (Hungria, et al) 3201 NDMM patients*: TTNT: 18.0 months vs NE RRMM patients*: TTNT: 14.9 vs 21.2 months CONNECT

*Ineligible patients had CRAB symptoms; †HOVON 87/VISTA/FIRST/SWOG S077; ‡STaMINA/IFM 2013-04/IFM DFCI 2009/EMN02 CI, confidence interval; CRAB, calcium, renal, anemia, bone; DSS, disease-specific survival; EHR, electronic health record; HR, hazard ratio; MM, multiple myeloma; NDMM, newly diagnosed multiple myeloma; NE, not evaluable; OS, overall survival; PFS, progression-free survival; RCT, randomized clinical trial; Rd, lenalidomide-dexamethasone; RRMM, relapsed and/or refractory multiple myeloma; TLN, tumor lymphatic neoplasms; TTNT, time to next therapy; Vd, bortezomib-dexamethasone

Terpos E, et al. BCJ 2021;11:40.

Racial Disparities in Access to Treatment and Clinical Trials for Patients with MM

African Americans with MM underrepresented in CAR T cell therapy trials

Clinical trial ineligibility rates across MM racial subgroups are higher among Black patients

PATIENT

• Age/Frailty

• Performance Status

• Lifestyle/Pt preferences

• Drug Metabolism

• Compliance/Adherence

• Caregiver support

• Renal Insufficiency

• Comorbidities

– Neuropathy

– Cardiac

– Diabetes

– Low blood counts

Unmet Needs in MM

DISEASE TREATMENT

Burden

• ISS/LDH

• Rate of rise

• Marrow burden

• CRAB symptoms

• Extramedullary

Biology

• Molecular - del[17p], t(4;14)

Trial Availability

If Previously Treated

• Depth/duration

• Relapse > 60d vs progression

Toxicity

• Myelosuppresion

• Neuropathy

• VTE

• Secondary cancers

Administration Route

Single or Combination

Cost and Copays

Access

What is the Future of Multiple Myeloma?

1. Smoldering Multiple Myeloma- To Treat Early/Cure or Not To Treat?

2. Will bone marrows ever go away?

3. Current unmet needs in MM requiring further effort

4. Moving Current Therapies Earlier/Novel Therapeutics

5. Treatment Free Intervals/Cure

Available Anti-Myeloma Agents in 2002

(When I Started Heme-onc Fellowship at UCSF)

Steroids Conventional Chemo

Prednisone Melphalan

Dexamethasone Cyclophosphamide

Doxorubicin

DCEP/D-PACE

METRO28

Carmustine

Bendamustine

Currently Available Anti-Myeloma Agents in 2024

Steroids Conventional Chemo ImIDs

Proteasome Inhibitors

Prednisone Melphalan Thalidomide Bortezomib

Dexamethasone Cyclophosphamide

Doxorubicin

DCEP/D-PACE

METRO28

Carmustine

Bendamustine

Lenalidomide Carfilzomib

Immunologic approaches

naked antibodies

Pomalidomide Ixazomib

Off label: venetoclax

Daratumumab (anti-CD38)

Isatuximab (anti-CD38)

Elotuzumab (anti-CS1)

Talquetamab anti-GPRC5d*CD3

Teclistamab anti-BCMA*CD3

Elranatamab anti-BCMA*CD3

idecabtagene vicleucel: anti-BCMA CART

ciltacabtagene autoleucel: anti-BCMA CART

XPO inhibitor

Selinexor

Overall Response Rate (ORR) and Progression Free Survival (PFS) of Recently Approved Therapies in RRMM

T cell redirection therapies

For > 4 LOT and IMID/PI/anti CD38 exposed

As of 4/5/24 CART approved for earlier LOT!

Ide-cel: 2-4 lines

Ciltacel: 1-3 lines

Pom/Dex Carf/Dex Dara Selinexor Talquetmab Teclistamab Elranatamab Ide-Cel Cilta-Cel

Richardson P et al Blood 2014;123(12):1826-32

Siegel DS et al. Blood 2012;120(14): 2817–2825

Lonial S et al. Lancet 2016;387:1551-1560

Chari A et al. N Eng J Med 2019;381:727-738

Touzeau et al EHA 2023

Nooka A et al ASCO 2022;abstract 8007 (oral presentation)

Lesohkin et al Nat Med 2023

Anderson L et al. ASCO 2021;abstract 8016 (poster presentation)

Usmani S et al ASCO 2022;abstract 8028 (poster presentation)

aThis is not a head-to-head comparison and cross-trial comparisons should not be interfered from these data Data represent two populations, PFS includes all patients, DOR includes responding patients only

Moving T cell Redirection Earlier – to Newly Diagnosed MM

Bispecific and Trispecific Engagers In Development

T cell Engagers

HPN217 (BCMA)

albumin

t½ extender

2:1 tumor:CD3 binding domain

Abbv-383 (BCMA)

NK cell Engagers

EMB-06(BCMA)

JNJ-79635322

(BCMA* GPRC)

low CD3 affinity trispecific tetravalent

IPH6401/SAR445514 ANKET BCMA/CD16/NKp46

CC-92328/DF3001 TriNKET BCMA/CD16/NKG2D

Tapia-Galisteo

CAR-Ts In Development

 Alternative manufacturing

o eg dd-BCMA – no neurotoxicity yet, EMD patients = non EMD

 Local manufacturing

 Academic CAR-Ts - $80k vs $500k for commercial CAR-T

 Fully human binding domains (vs mouse/llama)

 Allogenic off the shelf- no "brain to vein" time

 In-vivo CARs – viral injection into patient

 CRISPR (non viral) CART – phase 1 study soon @ UCSF!

 Non-BCMA targets eg GPRC5d, CD70

 Dual targets eg. GPRC5d+ BCMA, CD19 + BCMA

Other Novel Agents

 Cel-mods: Iberdomide, mezigdomide

 Antibody Drug Conjugates (ADCs): belantamab (anti-BCMA)

What is the Future of Multiple Myeloma?

1. Smoldering Multiple Myeloma- To Treat Early/Cure or Not To Treat?

2. Will bone marrows ever go away?

3. Current unmet needs in MM requiring further effort

4. Moving Current Therapies Earlier/Novel Therapeutics

5. Treatment Free Intervals/Cure

Lymphoma Envy- Disease Specific Therapies and Cures = Overall Survival of Patients Approaches That of Age Matched Controls

Follicular Lymphoma

Diffuse Large B

Cell Lymphoma

Flatter curve = More cures!

Multiple Myeloma

Hodgkins Lymphoma

MM “Cure Fraction” at 20 Years from International Myeloma Working Group

7291 MM patients from different clinical trials around the world who received ASCT

Cured fraction: 14%

How do we improve cure fraction for the vast majority of MM patients?

How do we identify cured patients and discontinue therapy?

An Early Surrogate Marker for Cure in MM: Looking Outside the Neoplastic Plasma Cell

Gene Expression Profiling of whole bone marrow biopsy material, which encompasses both hematopoietic (normal and

Complete Remission (CR), and normal donors

MM pts with CR status and whose bone marrow becomes normal donor-like (“normalization”) enjoy superior CR duration than those do not normalize

Identifying Patients Already Being Cured AKA Does Every MM Patient Need Treatment Indefinitely?

International Staging System

(albumin + beta 2 macroglobulin)

Revised2 ISS

(ISS + LDH + FISH including +1q)

What if we integrated

• Immune/marrow microenvironment

• extramedullary disease

• persistent renal failure

• frailty indices

• 50-75% of RRMM not eligible for clincial trials and have worse OS

• kinetic component – short vs durable remissions

• Known drug resistance with biomarkers

Can we use prognostic data to begin generating predictive data using risk adapted studies?

Increasing Cure Fraction In MM: Creating Bidirectional Connections and Shortening the Paths Between Silos

Myeloma Biology – Genomics, Clonal Heterogeneity, and Epigenetics

Clinical database linked to Tissue Bank including Novel Therapeutics

Microenvironment- Immunology

Iterative integration of patient characteristics, disease AND microenvironment characteristics + Novel therapeutics with mechanisms of resistance UCSF Global

Iterative patient level integration using machine learning

What Might a Route to a Cure in Multiple Myeloma Look Like?

Induction Post Induction Consolidation Maintenance

Suboptimal Response

15 mos post ciltacel

Weekly

Dara VRD

*4-6 cycles

MRD assessment & CD34 and T cell apheresis

BCMA CART

If functional high risk @ 3 mos post CART consolidation (ie <

MRD neg sCR or < 6 mos sust

MRD neg):

Tal + rev  *6  mos   then tec/tal *

6 mos then stop

If sust MRD neg * 12 mosobservation (target PFS > 48 mos)

if < sCR and/or < sust

MRD Neg * 12 mos: mel

200 ASCT

Curing Multiple Myeloma: Conclusions

√ Increasing novel mechanisms of myeloma killing and unprecedented potency of therapeutics

√ highly sensitive and specific disease detection to identify earlier detection of cured MM patients

√ Accurate risk stratification to identify cures and also iteratively identify unmet needs in era of novel therapeutics

√ Breaking the silos so that we can discontinue therapies in a sizeable % patients

Acknowledgements: Multiple Myeloma Team at UCSF

Patients and Caregivers

MDs

• Shagun Arora

• Ajai Chari

• Alfred Chung

• Anupama Kumar

• Tom Martin

• Nina Shah

• Peter Sayre

• Jeff Wolf

NPs/PAs

• Helen Diiulio

• Grace Sevilla

• Sam Shenoy (R)

• Nancy Wong

• Laura Zitella

Cellular Therapy Staff

• Jennifer Knoche

• Gabbi Perez

• Cheryl Slagle

RNs

Jennifer Brustein

Lisa Dunn

Katharina Ganapathi

Julie Mccluggage (R)

Jeani Wilmoth (R)

Samanha Zylberman (R)

Social Workers

• Nina Balsamo

• Isabel Curtin

• Rachel Dornhelm

• Judy Smoker

• Ana Zermeño

Dieticians

Medical Assistants

• Nashia Raley

• Joan Viyela

Pharmacists

• Richard Fong

• Mimi Lo

Administrative Staff

Deza Lynn Villanueva

Clinical Research Staff (R)

• Alicia Aschauer

• Mrugakshi Dave

• Edlimar Delgado

• Liam Gima-Lange

• Kenya Gomez

• Jenny Nguyen

• Lauren Nguyen

• Ruixin Sun

• Lena Truong

Translational Research Team

Julia Carnevale

Nupura Kale

Stefanie Bachl

Carter Ching

Justin Eyquem

Chang Liu

Joseph Muldoon

Alexis Talbot

Larry Fong

David Oh

Kai Wu

Arun Wiita

Nikhil Chilakapati

Szu-Ying Chen

Bonell Patiño Escobar

Haley Johnson

Corynn Kasap, Adila Izgutdina

Through our singular focus, we are leading revolutions in health.

EVALUATION

Please take a moment to reflect and respond to the program evaluation.

Questions 7 & 8 can be worked on after each presentation.

We greatly appreciate your time and feedback!

InfoLine Update

Teresa Miceli, RN, BSN, OCN

IMF InfoLine Advisor, Nurse Leadership Board Member; Mayo Clinic – Rochester, MN

IMF Update:

Teresa S. Miceli, RN BSN OCN

International Myeloma Foundation

Advisor

Hotline/InfoLine:

A Brief History

1990 – The first members of the IMF took patient calls and answered questions (Susie Novis, Dr. Durie, and Suzanne Battaglia) over 30 years ago!

2002 - The official “Hotline” was started (Debbie Birns and Nancy Baxter)

2014 - the Hotline was rebranded as the “InfoLine”.

Patients reach out to the InfoLine with questions and concerns

Common topics that come to the InfoLine include:

Education needs:

 MM101 and Understanding lab results

 New therapy information – Bispecifics, CART, side effects

 Publication requests

 Webinar & Meeting pre/post information

Emotional Support

 Grief and Loss

 General support

Financial concerns

 Medication and medical costs

 Daily living expenses

 Insurance coverage

Referral requests

 2nd opinion

 International access to care

 Clinical Trials

The InfoLine Team

Connection Between Patients and the IMF

The InfoLine Coordinators are the listening ear and voice of patient concerns. InfoLine Develo pment Suppo rt Group s Shippi ng Advoc acy

Provide support to patients in the moment and beyond

Be abreast of trending issues from the patient perspective

Review & revise current organizational activities to address the trending needs

“As a result of our conversation, I was able to have a second opinion … I just want to thank you for doing what you do! And for providing the information and support you did in our conversation. I felt so much better afterwards - more knowledgeable and more empowered - and was able to get the quality care I needed as a result.”

Patient Feedback to the InfoLine

“It was so nice speaking with you. Thank you for arranging the shipment of materials. It will be very helpful in the education of this disease.”

“With this information and the discussions, that I have had with the support nurses from Myeloma Australia regards clinical practice in both my home state of Western Australia & Victoria, I now feel well placed to have a discussion with my Haemotologist next week.”

“You have given us a better outlook on future possibilities and removed our concerns about what to expect.

Thanks, again. You and IMF are doing AWESOME work.”

BREAK

Reminder: After Break, return to designated Break-Out Room

Breakout Sessions #1: Treatment

Approaches in Myeloma

Newly Diagnosed: An Approach to Frontline Therapy

Caitlin Costello, MD Stanford

An Approach to Relapsed Myeloma

Amrita Krishnan, MD, FACP

Main Ballroom A/C

Approach To Relapsed Myeloma

Amrita Krishnan, MD, FACP Director of the Judy and Bernard Briskin Center for Multiple Myeloma Research

Executive Director, Hematology COH OC City of Hope Cancer Center

Evolution of Myeloma Therapy

Evaluation at Relapse

Bloodwork

• CBC and chemistry panel, including LDH, albumin, and corrected calcium

• Myeloma panel: quantitative immunoglobulins, SPEP, sFLC

• Consider 24 h urine for total protein, CrCl, UPEP, and UIFE

Imaging

• At symptomatic relapse: skeletal survey, PET/CT (alone or if skeletal survey is negative), WB LDCT, WB MRI

Bone Marrow

• Important to do a BM biopsy at the time of relapse

−

Reassess karyotype and FISH

Strategies for Refractory MM

Use prior therapies in new combinations

Novel agents

Salvage conventional chemotherapy

Stem cell transplantation (for select patients)

Clinical trial

Salvage Therapy; Ingredients

Treatment Disease Patient

• Age/frailty

• Performance status

• Lifestyle/patient preferences

• Drug metabolism

• Compliance/ adherence

• Caregiver support

• Renal insufficiency

• Comorbidities

- Neuropathy

- Cardiac

- Diabetes

- Low blood counts

Burden

• ISS/LDH

• Marrow burden

• Biochemical vs CRAB symptoms

• Rate of progression

• Extramedullary

Biology

• LDH elevation

• Molecular

- del[17p], t(4;14)

• Access/trial availability

• If previously treated

- Depth/duration

- Relapse >60 d vs progression

• Toxicity

- Myelosuppression

- Neuropathy

- VTE

- Secondary cancers

• Administration route

• Single or combination

• Cost and copays

Slide courtesy of A Chari.

Advanced Relapsed Myeloma

Therapy at First Relapse

• Discuss goals of therapy at relapse

• Overall S, QoL

• Triplet regimens are superior to doublet combinations

• Higher ORR

• Longer PFS

• Most patients are suitable for a triplet regimen

• Recent studies suggest an enhanced benefit for using aggressive triplet therapy in first relapse

• Dara/Len/Dex* Dara Pom Dex

• Dara Car Dex

• Isa Car Dex

• Isa Pom Dex

*Consider replacing Len with Pom, if patients is Lenrefractory.

Early Relapse: Phase 3 Study of DRd vs Rd in Patients With Relapsed or Refractory MM: POLLUX

Key eligibility criteria

• RRMM

• ≥1 prior line of therapy

• Prior lenalidomide exposure but not refractory

• Patients with creatinine clearance ≥30 mL/min

Stratification factors

• No prior lines of therapy

• ISS stage at study entry

• Prior lenalidomide

Cycles: 28 days

Primary end point

• PFS

Secondary end point

• TTP

• OS

• ORR, VGPR, CR

• MRD

• Time to response

• Duration of response

Carfilzomib, Dexamethasone, and Daratumumab vs Carfilzomib and Dexamethasone in RRMM:

Phase 3 CANDOR Study

Key inclusion criteria:

• Relapsed or refractory multiple myeloma

• 1–3 prior lines of therapy

• Partial response or better to ≥1 line

 Primary end point: PFS

KdD (n=312) Carfilzomib 56 mg/m2 IV (30 min)

28-day cycles until disease progression N=466

Days 1, 2, 8, 9, 15, 16 (20 mg/m2 days 1, 2, cycle 1 only)

Dexamethasone 40 mg (20 mg for patients >75 years old)

oral or IV once weekly

Daratumumab 8 mg/kg IV days 1, 2, cycle 1; 16 mg/kg

once weekly for remaining doses of cycle 1, 2, then every 2 weeks (cycles 3–6), then every 4 weeks

Kd (n=154)

Carfilzomib 56 mg/m2 IV (30 min)

Days 1, 2, 8, 9, 15, 16 (20 mg/m2 days 1, 2, cycle 1 only)

 Key secondary end points: OS, ORR, safety

Dexamethasone 40 mg (20 mg for patients >75 years old)

oral or IV once weekly

Updated Efficacy Results of the Phase 3 CANDOR Study; PFS !!

Dimopoulos MA et al. Blood. 2020;136: Abstract 2325.

IKEMA Study: A Phase 3 Randomized, Open-Label Study of Isatuximab + Carfilzomib and Dex vs Carfilzomib and Dex in RRMM

Stratification factors:

• Prior line 1 vs >1

• R-ISS: I or II vs III vs not classified

Relapsed MM

N=302

Isa-Kd (n=179)

• Isa: 10 mg/kg on D1, 8, 15, 22 in C1, then Q2W

• K: 20 mg/m2 D1–2; 56 mg/m2 D8–9, D15–16 C1; 56 mg/m2 D1–2, D8–9, D15–16 all subsequent cycles

• d: 20 mg D1–2, D8–9, D15–16 and D22–23 each cycle

Ran dom izati on

• 1–3 prior lines

• No prior therapy with carfilzomib

• Not refractory to prior anti-CD38

3: 2

Treatment until PD, unacceptable toxicities, or patient choice

Kd (n=123)

• K: 20 mg/m2 D1–2; 56 mg/m2 D8–9, D15–16 C1; 56 mg/m2 D1–2, D8–9, D15–16 all subsequent cycles

• d: 20 mg D1–2, D8–9, D15–16 and D22–23 each cycle

Primary end point: PFS (IRC)

Key secondary end points: ORR, rate of ≥VGPR, MRD negativity, CR rate, OS

Median PFS control arm estimated at 19 months Prespecified interim analysis when 65% PFS events (103) as per IRC

IKEMA Study: PFS benefit vs other ingredients

Isa-Kd: mPFS: NR (95% CI, NE–NE)

HR 0.531 (99% CI, 0.32–0.89)

P=0.0007

Kd:

mPFS: 19.15 months (95% CI, 15.770–NE)

Isa-Kd showed improvement in PFS with 47% reduction of risk of progression or death vs Kd.

Current Immunotherapy Landscape Late Relapse

 Belantama b

mafodotin

 Ide-cel

 Cevostama b  Talquetama b

 Elranatama b

 Cilta-cel

 Teclistamab

 CC-93269

 Daratumuma b

Orange denotes FDA and EMA approval

 Pre-clinical

 Isatuximab

FcRH5 GPRC5 D BCMA CD38

 Iberdomide

 CC-92480

CELMoDs: Pro-survival proteins

 Selinexo r

BAFF TACI

 Melfufen Nucleus

Exportin-1 mediated nuclear export

Peptideconjugated alkylator

© WebMD Global, LLC

BAFF, B-cell activating factor; BCMA, B-cell maturation antigen; CD, cluster differentiation; CELMoDs; cereblon E3 ligase modulator; FcRH5, Fc receptor-homolog 5; GPRC5D,G Protein-Coupled Receptor Class C Group 5 Member D; TACI, transmembrane activator and CAML interactor.

CITY OF HOPE

a. Adapted from Braunstein M, et al. Expert Rev Hematol. 2021;14:377-389; b. Sgherza N, et al. Front Oncol. 2021;11:716751.

New therapies

Bispecific antibodies, CAR T cells. Leadership in both spaces.

BCMA targeting

GPRC5D targeting

The Good News

FDA Approvals

 Oct 25 2022. Teclistamab-cqyv in the treatment of relapsed or refractory myeloma.

4 LOT

 Feb 28 2022. Ciltacabtagene autoleucel relapsed or refractory myeloma 4 LOT

 March 27 2021. Idecabtagene vicleucel relapsed or refractory myeloma 4 LOT

Autologous CAR T-Cell Therapy: Underlying Principles

Leukapheresis Manufacturing Infusion

Collect patient’s own

white blood cells

Isolate and activate Tcells

Tumor cell Activity

Engineer Tcells with CAR gene

Viral vector with CAR DNA CARengineere d T-cell

Targeting element

(eg, BCMA, CD19)

Spacer

Transmembrane domain

Costimulatory domain (eg, CD28 or 4-1BB)

CD3ζ (essential signaling domain)

Expand CAR T-cells

Infuse same patient with CAR T-cells

eg, BCMA, CD19

Median time from leukapheresis to product delivery: 32-33 days with cilta-cel and ide-cel Patients undergo lymphodepleting (and possibly salvage/bridging) therapy

Majors B et al. EHA 2018. Abstract PS1156. Lim QA et al. Cell. 2017;168(4):724-740. Sadelain M et al. Nat Rev Cancer. 2003;3(1):35-45. Brentjens RJ et al. Nat Med. 2003;9(3):279-286. Park JH et al. ASH 2015. Abstract 682. Ciltacabtagene autoleucel. Prescribing information. Janssen Biotech Inc;2022. Idecabtagene vicleucel. Prescribing information. Bristol Myers Squibb; 2021. Neelapu SS et al. N Engl J Med. 2017;377(26):25312544. Locke FL et al. N Engl J Med. 2022;386(7):640-654. Jacobson CA et al. Lancet Oncol. 2022;23(1):91-103. Wang M et al. N Engl J Med. 2020;382(14):1331-1342. Shah BD et al. Lancet. 2021;398(10299):491-502. Abramson JS et al. ASH 2019. Abstract 241. Kamdar M et al. Lancet. 2022;399(10343):2294-2308. Sehgal A et al. Lancet Oncol. 2022;23(8):1066-1077. Westin JR et al. Am J Hematol. 2021;96(10):1295-1312.

Phase II KarMMA: Idecabtagene Vicleucel in R/R MM

Lentiviral vector

Idecabtagene CAR design

Tumor-binding

Patients with R/R MM and ≥3 prior regimens each with ≥2 consecutive cycles, prior IMiD, PI, and anti-CD38 mAb, and refractory to last therapy by IMWG criteria (N = 158)

Leukapheresed n = 140

Idecabtagene vicleucel (n = 128)

150 x 106 CAR T-cells (n = 4)

300 x 106 CAR T-cells (n = 70)

450 x 106 CAR T-cells (n = 54)

 Primary endpoint: ORR

 Secondary endpoints: CRR, safety, DoR, PFS, OS, PK, MRD, QoL, HEOR

 Exploratory endpoints: immunogenicity, BCMA

expression/loss, cytokines, T-cell immunophenotype, GEP in BM

Baseline characteristics:

 High-risk cytogenetics: 35%

 Extramedullary disease: 39%



Median Follow-up, Mo

150 x 106 CAR T-cells: 18.0

300 x 106 CAR T-cells: 15.8

450 x 106 CAR T-cells: 12.4

Overall: 24.8

Median no. of prior therapies: 6 (range: 3-16)

 Triple refractory: 84%

KarMMa Phase 2 Study of Idecabtagene Vicleucel (Ide-Cel) in Patients

With RRMM: Efficacy. Response rates

 Median follow-up of 24.8 months (range, 1.7-33.6)

 Median time to first response of 1.0 months (range, 0.5-8.8)

 ORR did not vary by number of prior line of therapy (3 vs ≥4)

CARTITUDE-1: Ciltacabtagene Autoleucel for R/R MM

Single-arm, open-label phase Ib/II trial

Patients with R/R MM per IMWG and ≥3 prior regimens or double refractory to IMiD and PI and had received IMiD, PI, and anti-CD38 mAb (N = 113) Ciltacabtagene autoleucel (n = 97)

Baseline characteristics:

Contains 2 BCMA-targeting single-chain antibody designed to confer avidity

 High-risk cytogenetics: 23.7%

 Extramedullary disease: 13.4%

 Median no. of prior therapies: 6 (range: 3-18)

 Triple refractory: 87.6%

Landmark 2 Years Post-Last Patient-in Results of the CARTITUDE-1 Phase 1/2

Study of Cilta-Cel in Patients With RRMM: Efficacy1,2 Response and PFS ORR BY IRC PFS BY MRD AND RESPONSE STATUS

 Median DOR: NE (95% CI, 23.3 months-NE)

 Of 61 patients evaluable, 91.8% were MRD neg (10-5)

57%@27

 DOR, PFS, and/or OS were shorter in subgroups with HR cytogenetics, ISS III, and high burden

Data cutoff: January 11, 2022. Median follow-up: 27.7 months.

a 27-month PFS and OS rates.

BCMA CAR-T Pivotal Trials: Toxicities

* Delayed onset movement and neurocognitive symptoms noted in 12.4%, 9.3% Gr3 or higher.

Types of Monoclonal Antibodies

Drug Conjugates

radioactive isotope

Targe t cell

Target antigen (BCMA, CD38, etc)

• 2 antibodies or pieces of antibodies attached with 2 different targets

Bispecific T-Cell Engagers/Antibodies

Linker Linker

AMG420 AMG701

Light chains: 2

Heavy: Half-life extender

TNB-383 B

Light chains: 1

Heavy chains: 2

JNJ-7957 (DuoBody)

Light chains: 2

Heavy chains: 2 XmAb

CD3 binding site

BCMA binding site

Bispecific Antibody Therapy

• Mutual binding of MM cell and target cell antigen

• Activation of immune effector cells

• CD8+, CD4+, NK cells

CD3

T cell

CD3

PD-1

CD16

Yu L, Wang J. J Cancer Res Clin Oncol. 2019;145:941-956.

Target antigen

Targets in MM

Target cell

BCMA

SLAMF7

CD38

Teclistamab Overview

• FDA-approved in October 2022 for adults with R/R MM who have received ≥4 prior lines of therapy including a PI, an IMiD, and an anti-CD38 mAb

• Approval was based on results from MajesTEC-1, a phase 1/2 single-arm, multi-cohort, multicenter study

• Various teclistamab-containing combination regimens are being evaluated in clinical trials

https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-teclistamab-cqyv-relapsed-or-refractory-multiplemyeloma.

MajesTEC-1: Teclistamab in R/R MM: Efficacy

• ORR was consistent across subgroups, including patients with high-risk cytogenetics and pentarefractory patients

• MRD-negativity rate at 10-5:

• 26.7% in all-treated (N=165) population

• 81.5% of MRD-evaluable patients (44 of 54) were MRD-negative

• Median DOR, 18.4 mos

• Median PFS, 11.3 mos

Elranatamab Overview

• A humanized BCMA x CD3 bispecific antibody that induces a selective cytotoxic T-cell response targeting myeloma cells

• Phase 1 first-in-human MagnetisMM-1 trial is evaluating elranatamab in patients with R/R MM1

• Multiple phase 3 clinical trials are ongoing evaluating elranatamab as monotherapy and in combination with other active agents

MagentisMM-1: Elranatamab in R/R MM: Study Design

Phase 1 study is evaluating elranatamab SC at doses ranging from 215 to 1000 μg/kg in patients with R/R MM

Current analysis includes patients who received ≥215 μg/kg elranatamab (n = 55)

• Median age, 64.0 years (range, 42-80)

• 29.1% with high-risk cytogenetics

• Median of 5 prior lines of therapy (range, 2-14)

• 90.9% triple-class refractory

With 44 mg step-up priming plus premedication, overall incidence of CRS was 67%. CRS was further mitigated by 12/32 mg step-up priming in Phase 2 study (MagnetisMM-3)

What about other targets?

CD38 ADCs

CD38-targeted alpha interferon

GPRC5D

FCRH5

Talquetamab: First Approved GPRC5D×CD3 BsAb

• Talquetamab showed deep, durable responses and predictable safety in patients with RRMM, including patients with prior T-cell redirection therapy, at the RP2Ds

MonumenTAL-11-7; for the 0.8 mg/kg Q2W dose

‒ ORR: 71.7%4

‒ Median PFS: 14.2 mo5

• Comparable PFS in patients with high-risk vs standard-risk cytogenetics6

‒ Time to first and time to best response: 1.3 mo and 2.7 mo, respectively7

‒ Discontinuations: 8.3%4

• Exposure-response (E–R) analyses supported the RP2Ds: Increased ORR with subcutaneous doses that plateaued at or above the RP2Ds8

• E–R relationship observed for dysgeusia, with rates similar for both RP2Ds8

• Efficacy and safety profile support the appropriateness of the RP2D regimens

overall response rate; PFS, progression-free survival; Q2W, every other week; RP2D, recommended phase 2 dose; RRMM, relapsed/refractory multiple myeloma. 1. Verkleij CPM, et al. Blood Adv 2021;5:2196-215.

Talquetamab: Novel Off-Tumor, On-Target AEs

• GPRC5D-related AEs, including dysgeusiaa and skin (non-rash),b nail,c and skin (rash)d toxicities, are novel off-tumor, on-target AEs associated with talquetamab1

‒ In MonumenTAL-1, these toxicities occurred in up to 77%, 73%, 63%, and 40% of patients, respectively1

• Although >71% of patients responded to talquetamab, patients reporting ≥1 GPRC5Drelated AE in the first 90 days have a 20% increase in average likelihood of response (vs those who do not)

Here, we report safety and efficacy in patients with talquetamab dose reductions; these patients were treated at the RP2Ds and reduced dose once they achieved a response, to determine impact on GPRC5D-related AEs and maintenance of response

aIncludes ageusia, dysgeusia, hypogeusia, and taste disorder.  bIncludes skin exfoliation, dry skin, pruritus, and palmar-plantar erythrodysesthesia syndrome. cIncludes nail discoloration, nail disorder, onycholysis, onychomadesis, onychoclasis, nail dystrophy, nail toxicity, and nail ridging. dIncludes rash, maculopapular rash, erythematous rash, and erythema.  AE, adverse event; GPRC5D, G protein–coupled receptor family C group 5 member D; RP2D, recommended phase 2 dose. 1. Schinke CD, et al. Presented at ASCO; June 2–6, 2023; Chicago, IL, USA & Virtual. #8036.

Cevostamab Targets FCRH5

Cereblon E3 Ligase Modulators (CELMoDs): Novel Small-Molecule Inhibitors of Cereblon E3 Ligase

• Iberdomide (CC-220)

• Mezigdomide (CC-92480)

Iberdomide Mechanism of Action

• IBER enhances in vitro immune stimulatory activity vs LEN and POM1

IL-2 secretion by treated MM cell survival in co-culture with treated PBMCs1

DMSO, dimethyl sulfoxide; EC50, half maximal effective concentration; IL, interleukin; PBMC, peripheral blood mononuclear cell

Iberdomide in Combination With Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma: Results from the Dose-Expansion Phase of the CC-220-MM-001 Trial

Summary of responses

Iberdomide in Combination With Dex and Daratumumab, Bortezomib, or Carfilzomib in Patients With RRMM

Conclusions

Therapy of relapsed myeloma

-combinations

-immunotherapy backbones

-high response rates

-fixed duration

EVALUATION

Please take a moment to reflect and respond to the program evaluation.

Questions 7 & 8 can be worked on after each presentation.

We greatly appreciate your time and feedback!

Welcome Back

Newly Diagnosed Multiple Myeloma: What you need to know

Caitlin Costello, MD

Associate Clinical Professor of Medicine

UC San Diego

April 13, 2024

Multiple Myeloma Today

•An estimated 35,730 new cases of myeloma (19,860 males and 15,870 females) are expected to be diagnosed in the US in 2023.

•An estimated 157,561 people in the United States (US) are living with or in remission from myeloma.

CML, chronic myeloid leukemia; CLL, chronic lymphocytic leukemia; MM, multiple myeloma; NHL, non-Hodgkin lymphoma.

Leukemia & Lymphoma Society. Facts 2022-2023.

Available at: http://www.lls.org/#/resourcecenter/freeeducationmaterials/generalcancer/facts. Accessed April 11, 2024.

Multiple Myeloma Incidence Rates

SEER database: https://seer.cancer.gov/statfacts/html/mulmy.html, accessed 8/24/2023

Etiology: Risk Factors for MM

•Chronic exposure to low-dose ionizing radiation

•Occupational exposure (e.g. chemical)

•Genetic factors-increased MGUS risk in families

•Chronic antigenic stimulation (eg, recurrent infections and drug allergies)

•Agent orange, 9/11 exposure

•Ultimately, we do not know why patients develop MM

Multiple myeloma

Normal plasma cells proteins

Multiple myeloma cells

Bon e

Bone marrow

Ligh t chai Heavn y chain s

Ligh t chai n Antibodie s

Effects of Myeloma and Common Symptoms

Multiple Myeloma Complications.

Accessed April 14, 2016.

Campbell K.

Low Blood Counts

• Anemia is present in 60% of patients at diagnosis

• May lead to anemia and infection

Decreased Kidney Function

• Occurs in over half of myeloma patients

Bone Damage

• Affects 85% of patients

• Common sites include spine, pelvis, and ribs

• Leads to fractures

Bone Turnover

• Leads to high levels of calcium in blood (hypercalcemia)

Weakness

Fatigue Infection

Weakness

Bone pain

Loss of appetite

Weight loss

About 10% to 20% of patients with newly diagnosed myeloma will not have any symptoms.

http://www.themmrf.org/multiple-myeloma/multiple-myeloma-complications

Classification and Risk of Progression to Symptomatic Myeloma

MGUS, monoclonal gammopathy of undetermined significance; SMM, smoldering multiple myeloma.

*Timing is variable depending on individual risk factors

Kyle RA et al. Leukemia. 2010;24:1121

Diagnosing Myeloma:

Learn Your Labs!

Blood tests

• Number of red blood cells, white blood cells, and platelets

• Measure levels of albumin, calcium, lactate dehydrogenase (LDH), blood urea nitrogen (BUN), and creatinine. Assess function of kidney, liver, and bone status and the extent of disease.

• Determine the level of a protein that indicates the presence/extent of MM and kidney function

• Detect the presence and level of M protein

• Identify the type of abnormal antibody proteins

• Freelite® test measures light chains (kappa or lambda)

CBC, complete blood count; CMP, complete metabolic panel; B2M; beta-2 microglobulin; SPEP, serum protein electrophoresis; IFE, immunofixation electrophoresis; SFLC, serum free light chain assay

Urine tests

• Detect Bence Jones proteins (otherwise known as myeloma light chains)

• Determine the presence and levels of M protein and Bence Jones protein 24-hr Urine Analysis

Types of Monoclonal Protein (M Protein) in Multiple Myeloma

• For example:

• IgG+kappa

• IgG+lambda

• IgA+kappa

• IgA+lambda

• etc…

• 80% of myeloma cases

• Also known as Bence Jones protein

• 20% of all myeloma cases

• Renal failure more common in light chain multiple myeloma; creatinine >2 mg/dL in 1/3 of cases

• No monoclonal protein present

• 3% of cases of multiple myeloma

Diagnosing Myeloma:

Know Your Bone Marrow Tests!

Bone marrow aspiration and biopsy

Jamshidi needle

Bone marrow Ski n Hip bone

Chromosom

Conventional cytogenetic analysis

Karyotyping

FISH (fluorescence in situ hybridization)

Putting the Results Together

Imaging results

Blood and urine test results

Bone marrow analysis

Genomics

Staging, Diagnosis, and Prognosis

Updated IMWG Criteria for Diagnosis of Multiple Myeloma

MGUS

 M protein < 3 g/dL

 Clonal plasma cells in BM < 10%

Smoldering Myeloma

Multiple Myeloma

 M protein ≥ 3 g/dL (serum) or ≥ 500 mg/24 hrs (urine)

 Clonal plasma cells in BM

 No myeloma defining events

≥ 10% to 60%

 No myeloma defining events

 Underlying plasma cell proliferative disorder

 AND 1 or more myeloma defining events

 ≥ 1 CRAB* feature

 Clonal plasma cells in BM

≥ 60%

 Serum free light chain ratio ≥ 100

 > 1 MRI focal lesion

*C: Calcium elevation (> 11 mg/dL or > 1 mg/dL higher than ULN)

R: Renal insufficiency (creatinine clearance < 40 mL/min or serum creatinine > 2 mg/dL)

A: Anemia (Hb < 10 g/dL or 2 g/dL < normal)

B: Bone disease (≥ 1 lytic lesions on skeletal radiography, CT, or PET-CT)

Rajkumar SV, et al. Lancet Oncol. 2014;15:e538-e548.

Overview of Treatment Approach

MGUS

Close monitoring (observation) SMM

Close monitoring (observation)

If high risk: possible myeloma drugs (as part of a clinical trial)

Active myeloma

Initial therapy

• Myeloma drugs

• High-dose chemotherapy/stem cell transplantation (option, if possible)

Maintenance option

Therapies for relapsed/ refractory myeloma

If bone loss: bisphosphonates

Bone loss: bisphosphonates +

other supportive treatments

Clinical trial participation should be considered.

2015

2003-2013

Bortezomib

Lenalidomide

Thalidomide

Doxorubicin

Carfilzomib

Pomalidomide

Daratumumab

Elotuzumab

Ixazomib

Panobinostat

FDA-Approved Therapies for Multiple Myeloma

Selinexor

Belantamab

mafodotin

Daratumumab Sub-Q

Isatuximab

Idecabtagene

vicleucel

2022-2023 2022

Ciltacabtagene

autoleucel

Teclistimab

Talquetamab

Elranatamab

Most common current MM treatment plan:

Combine 2 to 3 drug classes and add dexamethasone

1. Center for Drug Evaluation and Research (U.S.) Drugs@FDA. Washington D.C.: U.S. Food and Drug Administration, Center for Drug and Evaluation Research.

D i a g n o s i s a n d R i s k S t r a t i f i c a t i o n F i t U n f i t / F r a i l o r D e c l i n e S C T

Tumor Burden

Multiple Myeloma Treatment Paradigm

MR D

Inductio n Induction followed by continuous therapy

Consolidatio n Managing Relapse Maintenanc e

Goals of therapy

• Immediately improve disease-specific symptoms

• Eradicate disease burden

• Obtain prolonged and durable remissions

• Save lives!

Factors Affecting Treatment Selection

Patient-Related

• Age/frailty

• Performance status

• Lifestyle/pt preferences

• Drug metabolism

• Compliance/adherence

• Caregiver support

• Renal insufficiency

• Comorbidities

Disease-Related

• ISS/LDH

• Rate of rise

• Marrow burden

• CRAB symptoms (hypercalcemia, renal failure, anemia, bone disease)

• Extramedullary

• Molecular cytogenetics/ genomics

Treatment-Related

• Response to prior therapy (depth/duration)

• Time to relapse

• Route of administration

• Single agent vs combination

• Adverse events/toxicity

• Clinical trial availability

• Costs and copays

• Access to standard of care therapies

Navigating the MM Drug Arsenal

Proteasome Inhibitors

Immunomodu latory Agents

Monoclonal Antibodies

Bortezomib (V)

Lenalidomi de (R)

Daratumum ab (D)

Carfilzomib (K)

Pomalidomi de (P)

Isatuximabirfc (Isa)

Ixazomib (I)

Thalidomid e (T)

Elotuzumab (E)

BCMASpecific Targets

Belantamab

mafodotinblmf (Bel)

Idecabtagen e vicleucel (Ide-cel)

Ciltacabtage ne autoleucel (Cilta-cel)

Small Molecule Inhibitors

Selinexor (X)

Corticosteroid s

Dexametha sone (d)

Venetoclax [if t(11;14)] (Ven)

Panobinost at (Pano)

Prednisone (p)

Drug Therapies in Multiple Myeloma

 Steroids

–

Dexamethasone, Medrol, Prednisone

– May be the most important drug to treat multiple myeloma

– Kills multiple myeloma cells

– Side effects:

• Weight gain, mood swings, irritability, fluid retention, skin thinning, cataracts, insomnia, muscle loss, raise blood sugars, hiccups

– Usually given as a pulse of treatment

•

Dexamethasone 40 mg every week

– Dose needs to be adjusted for each patient

Drug Therapies in Multiple Myeloma

 IMID’s – Lenalidomide (Revlimid)

• SE: Low blood counts, diarrhea, rash, muscle cramps – Pomalidomide (Pomalyst)

• SE: Low blood counts, fatigue, rash – All can increase risk for blood clots and cause birth defects if pregnant woman exposed to them

Drug Therapies in Multiple Myeloma

 Proteasome Inhibitors – Bortezomib (Velcade)

• Subcutaneous (shot in abdomen)

– Carfilzomib (Kyprolis)

• Intraveneous – Ixazomib (Ninlaro)

• Pill given weekly  Work by blocking protein breakdown in the cell

–

Plasma cells make protein as their main function

Daratumumab (Key takeaways)

 Antibody to CD38

– CD38 found seemingly universally on myeloma cells

– Humanized IgG Kappa antibody

• Will be detectable on SPEP, SIEP

– 0.1 – 0.2 g/dL protein spike often noted

 Single agent activity often combined with other agents

 Safety

–

–

10% infusion reaction on 1st injection

No other usual side effects

• ? Pancytopenia (mild), increased risk for infection

 Subcutaneous injection

 Takeaways:

– Well tolerated and easy to combine with other active drugs

– Shot version (Faspro) particularly well tolerated and without side effects

– Premedications can be stopped after a while

Initial Therapy Regimens for NDMM

Quadruplets are a new standard of care approach

D i a g n o s i s a n d R i s k S t r a t i f i c a t i o n F i t U n f i t / F r a i l o r D e c l i n e S C T

Tumor Burden

Multiple Myeloma Treatment Paradigm

MR D

Inductio n Induction followed by continuous therapy

Consolidatio n Managing Relapse Maintenanc e

Summary of Frontline MM Treatment Approach

Treatment Suggestions

 Goal is to maximize initial disease response (sCR, MRD[-])

 Backbone agents: steroids, PIs, IMiDs ± anti-CD38 mAbs

 Quad > triplet >>doublet regimens

 Choosing regimens  individual patient and tumor factors, prior exposure Tips for Transplant Patients

 Every patient who is a candidate should go to aHCT

 Age and renal function are not contraindications

 Limit exposure to myelotoxic agents and consider harvesting cells before prolonged exposure to lenalidomide and/or daratumumab Maintenance

 Given proven PFS ± OS benefit, maintenance remains important role

 Optimal duration varies (cost, toxicity, adherence, MRD status)

Key Steps to Take on Your Journey

Laboratory tests and diagnosis

Staging and prognosis

Obtain a second opinion

The promise of precision medicine

Partnering with the IMF

Sylvia Dsouza Vice President, Development

Partnering with the IMF

By Sylvia Dsouza, Vice President, Development

WHO AM I & WHAT DO I DO?

 Vice President of Development for the IMF

 Securing support and resources for the IMF through diverse mechanisms

 Oversee a team of passionate and determined fundraising professionals who are committed to advancing the mission and of the IMF

The Mission and Impact of the IMF

Our Mission: Since our inception more than 30 years ago, the International Myeloma Foundation has been the leading force in the fight against multiple myeloma. The IMF’s reach extends to 525,000 members in 140 countries, including patients, caregivers, healthcare professionals, researchers, and more. Together, we are One Myeloma Nation – a global community focused on improving the quality of life of myeloma patients while working toward prevention a cure.

Our Impact: The International Myeloma Foundation takes a multiple-pronged approach to attacking this disease on a global front as well as being a pillar of support to the myeloma patient and caregiver community.

• Accelerate the discovery of new therapies available to patients, including playing a part in the approval of 15 new myeloma drugs in the last decade alone.

• Advance research through innovation - Black Swan Research Initiative® (BSRI) that has more than 50 ongoing, concurrent projects happening globally.

• IMF’s BSRI’s iStopMM is “the largest single-country, randomized trial that has ever been conducted in the cancer field.”

• Bring more than 250 leading, global myeloma experts together under one roof - the IMF’s International Myeloma Working Group (IMWG)

IMF's Four Pillars

• Amplify the voices of cancer patients worldwide by guiding individuals to advocate for critical issues that affect the myeloma community

• Lead cancer patient advocacy coalitions at the state, federal, and global levels

• Collaborate with more than 30 cancer organizations to influence oral chemotherapy parity legislation as well as global access to novel therapies for all cancer patients

• Ensure access to care for underserved and underrepresented populations through our M-Power Initiative.

• Design and Execute Patient and Family Seminars to patients and their loved ones.

• Meet the needs of smaller communities with Regional Community Workshops

• Highlight timely health and wellness issues with Living Well with Myeloma webinars that cover everything from exercise, nutrition, financial well-being, and more.

• Publish a library of more than free 100 resources and nearly 20 translations

• Help facilitate and maintain a network of more than 150 support groups in North America, with the knowledge that patients involved in a support group experience. more positive outcomes in the course of their disease

• Service patients for immediate concerns in a caring and compassionate manner through our InfoLine phone and email lines.

• Help a support group and become a support group leader.

Become a Partner, Be a Change Agent

Peer-to-Peer Fundraising

• Peer-to-Peer Fundraisers are created from YOUR ideas. Starting a Fundraiser is easy and fun. They also make a world of difference in the myeloma community.

• Engage your family, friends, co-workers, your network who honor your journey with myeloma and want to support you. Let them show you that you are not alone.

Join the HOPE Society (Recurring Monthly & Annual Giving Program)

• Help us cultivate the future by joining the International Myeloma Foundation's Hope Society.

• Monthly gifts starting at $10 support IMF core programs, including educational events, publications, the toll-free InfoLine, and more.

• Turn your monthly contribution into a yearly commitment.

Transformative Gifts (Major Giving and Principal Giving)

• Gifts can be designated toward a specific program or service.

 Unrestricted, Direct and Endowment

What will your legacy be?

Planned Giving

• Join the Brian D. Novis Legacy Society and make a planned gift!

• Gain immediate tax benefits

• Potentially increase your income during your lifetime.

• Continue to fund our core programs and four pillars.

• Make a bequest (a gift from your estate)

• Include a provision in your will or living trust.

• Designated us as a beneficiary of a life insurance policy, or retirement plan (IRA, 401(k), or 403(b).

• Leave us in your will is one of the most profound ways to support the people and causes important to you.

Corporate and Foundation Gifts

• Your organization can contribute a corporate gift or foundation grant

• Provide seed funding that is necessary to accelerate the path to a cure.

3 Ways to Engage

Philanthropy

• Make a donation to support research, patient programs, and advocacy efforts.

• Sponsor or participate in fundraising events such as walks, runs, or galas.

• Create a fundraising campaign online to raise awareness and funds.

Community/network

• Join your local support group/become a Support Group Leader

• Volunteer your time through mentorship or support programs.

• Engage on social media to connect with others affected by myeloma.

Intellectual capacity

• Attend conferences/webinars to stay updated on the latest news.

• Offer your expertise as a speaker or panelist at events.

Start the Conversation

We welcome you to continue to learn more about our programs, projects, and initiatives at the IMF and find alignment with your own myeloma journey as well as ways to deepen and strengthen your engagement with us.

Reach out to the IMF Development Team to start a conversation on how you can make a difference in the lives of the people impacted by myeloma.

•Sylvia Dsouza - IMF Vice President, Development

sdsouza@myeloma.org | 818.487.7455 ext. 268

•Ilana Kenville - IMF Director of Development, Peer-to-Peer Fundraising

ikenville@myeloma.org | 818.487.7455 ext. 272

•Matthew Broughton - IMF Assistant Director of Development

mbroughton@myeloma.org | 818.487.7455 ext. 299

IMF Development Team

Sylvia Dsouza

Vice President, Development

Matthew Broughton

Assistant Director of Development Ilana Kenville

Director of Development, Peer-to Peer Fundraising

QUESTIONS?

Seasons of Multiple Myeloma

Deborah Doss, RN, OCN

Dana Farber Cancer Institute

IMF Nurse Leadership Board Member

Wintery Mix of Treatment Options Spring into Managing Side Effects

Wintery Mix of Treatment Options

Diverse and Complex Treatment Combinations

Myeloma Treatment

Velcade® (bortezomib)

Lenalidomide

Kyprolis® (carfilzomib)

Pomalyst® (pomalidomide)

Darzalex® (daratumumab)

Common Combinations

DVRd, VRd, Vd

DVRd, VRd, Rd

KRd, Kd, DKd, Isa-Kd

Pd, DPd, EPd, PCd, Isa-Pd

DVRd, DRd, DVd, DPd, DVMP, DKd

Ninlaro®(ixazomib) IRd

Empliciti® (elotuzumab)

Xpovio® (Selinexor)

Sarclisa® (Isatuximab)

ERd, EPd

XVd, XPd, XKd

Isa-Kd, Isa-Pd

Blenrep® (Belantamab mafodotin) Bela-d

Abecma® (Idecabtagene Vicleucel) --

Carvykti™ (ciltacabtagene autoleucel) --

Elrexfio™ (elranatamab) --

Tecvayli® (teclistamab)

Talvey™ (talquetamab)

Venclexta® (venetoclax)

Vd + ven

New agents or regimens in clinical trials are possible options

ASCT = autologous stem cell transplant; Bela = belantamab; C = cyclophosphamide; D = daratumumab; d = dexamethasone; E = elotuzumab; Isa = isatuximab; I = ixazomib; K = carfilzomib; M = melphalan; P = pomalidomide; R = lenalidomide; V = bortezomib; ven = venetoclax.

Prescribing information. NCCN Guidelines. Multiple Myeloma. V2.2024. Accessed February 5, 2024.

Stem Cell Transplant

ELIGIBILITY

Measuring Treatment Response

Determining Transplant

Eligibility

Insurance Authorization

Collecting Stem Cells

Duration: Approximately 2 weeks

Location: Transplant Center

TRANSPLANT

High Dose Chemotherapy Stem

Cell Infusion Supportive Care Engraftment

Duration: Approximately 3-4 weeks

Location: Transplant Center

POST-TRANSPLANT

Restrengthening

Appetite recovery

“Day 100” assessment

Begin maintenance therapy

Duration: Approximately 10-12 weeks

Location: HOME

Upfront stem cell transplant remains the standard of care for eligible patients

CAR T: Another Treatment Approach

Ask for a referral to CAR Tcell center as soon as it is possible as next treatment option (ie, before relapse)

Manufacturing takes ≈ 4 to 6 weeks

Bridging therapy may be needed

T-Cell Collection

No driving for 8 weeks

“One & Done” with continued monitoring

• Away from home

• Often some hospital stay

• Care Partner needed

• Side effect management

• CRS, ICANS

• Low blood counts

• Fatigue and fever

• Some patients need ongoing transfusion support

Bispecific Antibodies

•Different bispecific antibodies have differences in efficacy, side effects

– Available after 4 prior lines of therapy (or clinical trial)

– About 7 in 10 patients respond

– Off-the-shelf treatment; no waiting for engineering cells

– CRS and neurotoxicity

– Risk of infection

•BCMA target: greater potential for infection

– Tecvayli® (teclistamab)

– Elrexfio™ (elranatamab)

BISPECIFIC ANTIBODIES

Cytotoxic cytokines

•GPRC5D target: potential for skin and nail side effects, GI issues of taste change, anorexia and weight loss

– Talvey™ (talquetamab)

Bispecific antibody T

MM cell death Target CD3

CAR = chimeric antigen receptor.

Brudno JN, Kochenderfer JN. Blood. 2016;127(26):3321-3330. Lee DW, et al. Biol Blood Marrow

Transplant. 2019;25:625-638.

Spring Into  Managing  Side Effects

The Early Bird Gets the Worm: Communicate Proactively with Your Healthcare Team

Your team may be able to help, but only if they know how you feel.

Unmanaged Myeloma can cause:

Calcium elevation

Renal dysfunction

Low blood counts

Infection Risk

Blood clots

Bone pain

Neuropathy

Fatigue

Side Effects of Treatment can cause:

GI symptoms

Renal dysfunction

Low blood counts

Infection Risk

Blood clots

Neuropathy

Fatigue

Tip: proactively discuss common side effects and what to do if they occur

Are Steroids Messing With Your Sunny Disposition?

Steroids enhance the effectiveness of other myeloma therapies

Your provider may adjust your dose. Do not stop or alter your dose of steroids without discussing it with your provider

Steroid Side Effects

• Irritability, mood swings, depression

Managing Steroid Side Effects

•Consistent schedule (AM vs. PM)

•Take with food

•Stomach discomfort: Over-the-counter or prescription medications

•Medications to prevent shingles, thrush, or other infections

• Difficulty sleeping (insomnia), fatigue

• Blurred vision, cataracts

• Flushing/sweating

• Increased risk of infections, heart disease

• Muscle weakness, cramping

• Stomach bloating, hiccups, heartburn, ulcers, or gas

• Weight gain, hair thinning/loss, skin rashes

• Increased blood pressure, water retention

• Increased blood sugar levels, diabetes

Infection Can Be Serious for People With Myeloma

[P]reventing infections is paramount.

Infection remains the leading cause of death in patients with multiple myeloma. Several factors account for this infection risk, including the overall state of immunosuppression from multiple myeloma, treatment, age, and comorbidities (e.g., renal failure and frailty).

IMWG Consensus guidelines and recommendations for infection prevention in multiple myeloma; Lancet Haematol.2022;9(2):143–161.

Good personal hygiene (skin, oral)

Environmental control (avoid crowds and sick people; use a high-quality mask when close contact is unavoidable)

Infection Prevention Tips IMWG = International Myeloma Working Group; HCP = healthcare provider.

Report fever of more than 100.4°F, shaking chills even without fever, dizziness, shortness of breath, low blood pressure to HCP as directed.

As recommended by your healthcare team:

Immunizations:

Flu, COVID, RSV & and pneumococcal vaccinations; avoid live vaccines

Preventative and/or supportive medications (next slide)

Medications Can Reduce Infection Risk

Type of Infection Risk

Viral: Herpes Simplex (HSV/VZV); CMV

Bacterial: blood, pneumonia, and urinary tract infection

PJP (P. jirovecii pneumonia)

Fungal infections

COVID-19 and Influenza

IgG < 400 mg/dL (general infection risk)

ANC < 1000 cells/μL (general infection risk)

Medication Recommendation(s) for Healthcare

Team Consideration

Acyclovir prophylaxis

Consider prophylaxis with levofloxacin

Consider prophylaxis with trimethoprim-sulfamethoxazole

Consider prophylaxis with fluconazole

Antiviral therapy if exposed or positive for covid per institution recommendations

IVIg recommended

Consider GCSF 2 or 3 times/wk (or as frequently as needed) to maintain ANC > 1000 cells/μL and maintain treatment dose intensity

Some people receiving BCMA-targeting therapies have experienced infections that are less common like CMV, PJP and fungal infections

ANC = absolute neutrophil count; BCMA = B-cell maturation antigen; CAR = chimeric antigen receptor; CMV, cytomegalovirus; GCSF = granulocyte colony-stimulating factor; HSV = herpes simplex virus; IVIg = intravenous immunoglobulin; PJP = Pneumocystis jirovecii pneumonia; VZV = varicella zoster virus. Raje NS, et al. Lancet Haematol.2022;9(2):143–161.

Management of Oral Side Effects

Dry Mouth

Taste Changes

OTC dry mouth rinse, gel, spray are recommended. Advise patients to avoid hot beverages. Initiate antifungal therapy for oral thrush

Dexamethasone oral solutions “swish and spit” have been tried but with no proven benefit yet. Sour citrus or candies before meals are also recommended.

Dental Care

Attention to oral hygiene. Regular dental cleaning and evaluation. Close monitoring for ONJ, oral cancer and dental caries

Dysphagia

Dietary modifications with small bites, eating upright, and sips with food can help manage symptoms.

Weight Managemen t

Some medications lead to weight gain, others to weight loss.

Dry mouth leads to taste changes which can lead to anorexia.

Meet with a Nutritionist

Consider diet changes, supplements

Monitor weight

Education and emotional support are key strategies to manage oral toxicities.

OTC = Over The Counter

ONJ = Osteonecrosis of the Jaw

GI Symptoms: Prevention & Management

Fluid intake can help with both diarrhea and constipation and helps kidney function

Diarrhea may be caused by medications and supplements

•Laxatives, antacids with magnesium

•Antibiotics, antidepressants, other (check with provider, pharmacist)

•Supplements: milk thistle, aloe, cayenne, saw palmetto, ginseng

Avoid caffeinated, carbonated, or heavily sugared beverages

Take anti-diarrheal medication if recommended and no cause related to infection

Constipation may be caused by medications and supplements

•Opioid pain relievers, antidepressants, heart or blood pressure medications (check with provider, pharmacist)

•Supplements: Calcium, Iron, vitamin D (rarely), vitamin B-12 deficiency

Increase fiber

•Fruits, vegetables, high fiber whole grain foods

•Fiber binding agents – Metamucil®, Citrucel® , Benefiber®

Discuss GI issues with healthcare providers to identify causes and make adjustments to medications and supplements

Skin and Nail Side Effects

Possible side effect to some treatments and supportive care medications

Skin Rash:

•Prevent dry skin; apply lotion

•Report changes to your care team

•Medication interruption or alternative, as needed

•Steroids:

– Topical for grades 1-2,

– Systemic and topical for Grade 3

•Antihistamines, as needed

Photos: Mount Sinai Hospital, NY, NY

Nurse Leadership Board

Nail Changes:

•Keep your nails short and clean.

Watch for “catching and tearing”

•Apply a heavy moisturizer like Vaseline or salve.

Wear cotton hand coverings to bed

•A nail hardener may help with thinning

•Tell the team if you have signs of a fungal infection, like thickened or discolored nails

Feel Like a Spring Chicken: Prevent and Manage Pain

Pain can significantly compromise quality of life

Sources of pain include bone disease, neuropathy and medical procedures

•Management

– Prevent pain when possible

• Bone strengtheners to decrease fracture risk

• Antiviral to prevent shingles

• Sedation before procedures

– Interventions depend on source of pain

• May include medications, activity, surgical intervention, radiation therapy, etc

• Complementary therapies (Mind-body, medication, yoga, supplements, acupuncture, etc)

• Scrambler therapy for neuropathy

Tell your healthcare provider about any new bone or chronic pain that is not adequately controlled

Peripheral Neuropathy Management

Peripheral neuropathy happens when there is damage to nerves in the extremities (hands, feet, limbs). Damage can be the result of myeloma, treatment or unrelated conditions (i.e. diabetes).

Symptoms:

•Numbness

•Tingling

•Prickling sensations

•Sensitivity to touch

•Burning and/or cold sensation

•Muscle weakness

Prevention / management:

•Bortezomib once-weekly and/or subcutaneous administration

•Massage area with cocoa butter regularly

•Neuroprotective Supplements:

– B-complex vitamins (B1, B6, B12)

– Green tea

•Safe environment: rugs, furnishings, shoes

If neuropathy worsens, your provider may:

•Adjust your treatment plan

•Prescribe oral or topical pain medication

•Suggest physical therapy

Report symptoms of peripheral neuropathy early to your healthcare provider; nerve damage from neuropathy can be permanent if unaddressed

Understanding Changes to Kidney Function

•Risk Factors

– Active multiple myeloma (light chains, high calcium)

– Other medical issues (ex: Diabetes, dehydration, infection)

– Medications (MM treatment, antibiotics, contrast dye)

– Poor Nutrition

•Prevention

– Stay hydrated – drink water

– Avoid certain medications when possible (eg, NSAIDs), dose adjust as needed

•Treatment

– Treatment for myeloma

– Hydration

– Dialysis

Many myeloma patients will experience kidney issues at some point; protecting your kidney function early and over time is important

Additional Supportive Care

Supportive Medications

DVT/PE Prevention

Blood thinners

Ex: Aspirin, DOACs

Bone Health Fatigue Anxiety

Bone Strengthening Agents

Calcium

Vitamin D

Stimulant medications

Red Cell Transfusion (anemia)

Anti-depressants

Summer of Success

Let the Sun Shine In

98.8%

Fatigue

Fatigue is the most reported symptom.

Sources include anemia, pain, reduced activity, insomnia, treatment toxicity, bone marrow suppression

Often, people do not share these symptoms with their providers. Talk to your provider about symptoms that are not well controlled or if you have thoughts of self-harm.

Depression Anxiety

>35% of patients

Help is available.

≈ of patients

Care Partners Are Vital for Success

If you want to go fast, go alone, if you want to go far, go together African Proverb

•Care partners may help with medical appointments, managing medication, daily living, physical assistance, emotional support, myeloma knowledge, healthy lifestyle, patient advocacy, financial decisions

•Care partners can be a spouse, close relative, a network of people (family, friends,

•Caring for the Care Partner

– Recognize that caregiving is difficult/stressful

– Encourage care partners to maintain their health, interests, and friendships

– The IMF has information and resources to help care partners

Cultivate A Care Network

•Multiple studies demonstrate that strong social ties are associated with

– Increased longevity including people with cancer

– Improved adherence to medical treatment leading to improved health outcomes

– Lower risk of cardiovascular diseases

– Increased sense of purpose & life satisfaction

– Improved mood and happiness

– Reduced stress and anxiety

– Enhanced resilience

Martino J, et al. Am J of Lifestyle Med. 2015;11(6):466-475. Yang YC, et al. Proc Natl Acad Sci U S A. 2016;113(3):578583.

Pinquart M and Duberstein PR. Crit Rev Oncol Hematol. 2010; 75(2):122–137.

•Strategies for enhancing social connection

–

–

Deepen existing relationships with family, friends, and loved ones

Build new relationships by participating in a support group, joining clubs or organizations, or volunteering

Tip: Start with small steps outside your comfort zone. Call a loved one you haven’t spoken to in a while. Invite a person you’d like to know better for lunch, coffee, or a walk.

Hetherington C. Healthnews.

https://healthnews.com/longevity/healthspan/social-connection-andlongevity/#:~:text=Research%20consistently%20demonstrates %20that%20people,of%20fulfillment%20in%20your%20life. Accessed Feb 1 2024.

Enjoy Life’s Bounty

Harvest Good Health

Have a Primary Care Provider & Have Recommended Health Screenings

• Blood pressure

• Cholesterol

• Cardiovascular disease

• Diabetes

• Colonoscopy

• Women specific: mammography, pap smear

• Men specific: prostate

• Vision

• Hearing

• Dermatologic evaluation

• Dental checkups & cleaning

BOUNTY

Develop & maintain healthy behaviors

Good nutrition

Regular activity

Quit tobacco use

Sufficient Sleep (next slide)

An ounce of prevention is worth a pound of cure.

Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Dimopoulous M, et al. Leukemia. 2009;23(9):1545-56. Brigle K, et al. CJON. 2017;21(5)suppl:60-76. Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Faiman B, et al. CJON. 2011;15suppl:6676. Miceli TS, et al. CJON. 2011;15(4)suppl:9-23.

Benjamin Franklin

Plentiful Sleep: Important for Good Health

•Adequate rest and sleep are essential to a healthful lifestyle

•Shortened and disturbed sleep cause

– Increased heart-related death

– Increased anxiety

– Weakened immune system

– Worsened pain

– Increased falls and personal injury

•Things that can interfere with sleep

– Medications: steroids, stimulants, herbal supplements

– Psychologic: fear, anxiety, stress

– Physiologic: sleep apnea, heart issues, pain

• Sleep hygiene is necessary for quality nighttime sleep and daytime alertness

– Engage in exercise but not too near bedtime

– Increase daytime natural light exposure

– Avoid daytime napping

– Establish a bedtime routine - warm bath, cup of warm milk or tea

•Associate your bed ONLY with sleep

– Avoid before bedtime:

• Caffeine, nicotine, alcohol and sugar

• Large meals and especially spicy, greasy foods

• Computer screen time

•Sleep aid may be needed

EVALUATION

Please take a moment to reflect and respond to the program evaluation.

Questions 7 & 8 can be worked on after each presentation.

We greatly appreciate your time and feedback!

Health Disparities in Myeloma

Patient and Family Seminars

Joseph Mikhael MD, MEd, FRCPC

Chief Medical Officer, International Myeloma Foundation

Professor, Translational Genomics Research Institute, City of Hope Cancer Center

What are Health Disparities?

•Health disparities are preventable differences in the burden of disease, injury, violence, or opportunities to achieve optimal health that are experienced by socially disadvantaged populations

- Centers for Disease Control (CDC)

•Health equity generally refers to individuals achieving their highest level of health through the elimination of disparities in health and health care

What are the DRIVERS of Disparities in MM?

1. Systemic racism

2. The Healthcare system

3. Social Determinants of Health

4. Biology of the disease and concomitant comorbidities

5. Delayed Diagnosis

6. Access to Care – Triplets, Transplants, Trials and Car T

7. Lack of diversity, cultural sensitivity and optimal communication in healthcare professionals

A Call to Action

Facts About African Americans and Myeloma

1. There is a longer time from symptoms to diagnosis among African Americans

2. African Americans and Latino Americans are about 5-6 years younger at diagnosis

3. MM and MGUS are more than 2x as common in African Americans

4. African Americans and Latino Americans are less likely to receive the FOUR T’s: Transplant, Triplets, Trials and CAR Ts

5. African Americans have biologic differences with more t(11;14) and less high-risk cytogenetics with deletion 17p

6. Survival outcomes in African Americans are HALF of what is seen in White Americans

7. African Americans can achieve equal or better outcomes when they receive therapy

What are the DRIVERS of Disparities in MM?

1. Systemic racism

2. The Healthcare system

3. Social Determinants of Health

4. Biology of the disease and concomitant comorbidities

5. Delayed Diagnosis

6. Access to Care – Triplets, Transplants, Trials and CART

7. Lack of diversity, cultural sensitivity and optimal communication in healthcare professionals

M-Power = Myeloma Power

The core vision of this initiative is to improve the short- and longterm outcomes of African American patients with myeloma. We want to empower patients and communities to change the course of myeloma…

ENHANCE

ENGAGE

Engage the community to increase awareness and provide support

M-Power

EDUCATE

Shorten the time to diagnosis by educating primary care providers to recognize the disease and order the right tests Enhance access to optimal care by educating myeloma providers about the disparity and how to reduce it

You can learn more at mpower.myeloma.org

M-Power Is Both a National and Local Movement

Local Efforts

Grand Rounds MD

Collaborate with key Stakeholders

National Efforts

Free CE course for PCPs

Social Media Campaigns

Community Workshops

Community events

Publications

Free CE course for Nurses

Educational Postcards

Mentorship of Medical Students

Facebook Live

2023 M-Power Community Workshops

April 1, 2023

50+ attended

81% African American

• 100% rated v good or excellent

• 100% learned something new!

June 17, 2023

50+ attended

68% African American

September 24, 2023

35+ attended

41% African American

75+ attended

61% African American

• 80% at the Grace Baptist Church learned of the Workshop through their congregation

• 63% at the Riverside Church location learned of the Workshop from IMF

• 96% of attendees

rated the program as excellent

• 92% of the attendees

reported learning something new

• 100% plan to share something they learned

• 76% had not previously attended an IMF program

Facebook Live

Education of Primary Care Providers

Our goal is to reduce DELAYS in diagnosis among African Americans by educating the primary care community with a focus on:

• Recognizing the signs and symptoms of myeloma

• Discriminating myeloma from other diagnoses such as diabetes

• Capturing an accurate diagnosis through proper use of testing

• Providing referral guidelines for Hematology and Oncology

• Grand Rounds

• Postcards mailed to 6,000+ PCPs in target cities

• Free PCP CME course “Don’t

Miss Myeloma”

• Cobb Institute talk

Talk at NMA Annual Meeting

Articles and pending publications

8,000 Learners

Annual Meeting of the National Medical Association

Jane Cooke Wright Symposium on Health Disparities

• Hosted by Dr. Edith Mitchell

• Keynote speaker - Dr. Monica Bertagnolli, the director of the National Cancer Institute (NCI)

• Dr. Mikhael spoke about health disparities in myeloma

Poster Walk

Student research was presented to Yelak Biru, Dr. Mikhael, Dr. Mitchell, Dr. Morgan (CEO of the Cobb Institute) and Dr. Bertagnolli.

M-Power Connections

M-Power Website:

•Web Stats: Over 40k Page views across main, city sites & myeloma.org

•Google PPC targeted web traffic

Email Stats:

•Total Sent: 18 emails

•Total Audience: 38k*

•Open Rate Avg: 31%*

*Note: We have continued to refine lists, contributing to a more engaged audience as evidenced in the Open Rates (The industry standard high-mark is 21%).

M-Minute Promotion

Stats:

•Total Sent: 19 emails

•Total Audience: 323k

•Open Rate Avg: 38.91%

M-Power Related Video

Stats:

• Total Views: Over 50k

Engage

• Planning for 2024 workshops in New York (Juneteenth) and other cities

• Expand online and social media strategy

Future Direction s

Educate

• Primary care program in Charlotte

• Lab based education

• Electronic Medical Record Initiative

Enhance

• Rolling out the Clinical Trial Mentor (CTM) as part of the Diversity in Clinical Trials initiative

• Nurse equity decision tool

Conclusions

•Health disparities are sadly prevalent across all diseases, but particularly in multiple myeloma

•There are MANY other types of inequity in myeloma, including geography, age, gender, orientation…

•Being aware of these disparities is critical to overcoming them

•The IMF’s M-Power is designed to reduce the inequity with specific emphasis on delayed diagnosis, access to therapy and diversity sensitive clinical care

What Can I Do??

•Be more conscious of the topics of health equity

•Evaluate the opportunities in your experience to reduce disparities

•Support the M-Power movement! mpower.myeloma.org

EVALUATION

Please take a moment to reflect and respond to the program evaluation.

Questions 7 & 8 can be worked on after each presentation.

We greatly appreciate your time and feedback!

Saturday Agenda: Afternoon

12:00 – 1:00 PM LUNCH

Reminder: After Lunch, return to designated Break-Out Room

1:00 – 1:40 PM Breakout Sessions #2:

Patients and Care Partners

1:40 – 1:45 PM RETURN TO GENERAL SESSION

1:45 – 2:15 PM Wild Card Topic: Practical Aspects of Immunotherapy

Ajai Chari, MD; University of California San Francisco

2:15 – 2:55 PM Ask – the – Experts with Guest Faculty

Breakout A: Patients Only – Lessons Learned

Facilitators: Michael Tuohy - 24-year Myeloma Survivor & Patient Advocate,

Support Group Leader

Yelak Biru, 28-year Myeloma Survivor Patient

Main Ballroom: B/C

2:55 – 3:00 PM Closing Remarks & Program Evaluation

Breakout B: Care Partners Only

Facilitators: Robin Tuohy & Teresa Miceli

Ballroom D: Drake

Breakout Sessions #2: Patients and Care Partners

Patients Only – Lessons Learned

Michael Tuohy & Yelak Biru

Main Ballroom A/C

Care Partners Only

Robin Tuohy & Teresa Miceli Stanford

LUNCH

Reminder: After Lunch, return to designated Break-Out Room

Patients Only – Lessons Learned

Michael Tuohy & Yelak Biru

Practical Aspects of Immunotherapy

Ajai Chari, MD

University of California San Francisco

Practical Aspects of Immunotherapy

Ajai Chari, MD

Professor of Clinical Medicine

Director of Multiple Myeloma Program

Co-Director of Clinical Research, Hematology Oncology

University of California, San Francisco

Currently Available Anti-Myeloma Agents in 2024: T cell Redirection Immune Therapies

Steroids Conventional Chemo ImIDs

Proteasome Inhibitors Immunologic approaches

Prednisone Melphalan Thalidomide Bortezomib

Dexamethasone

Cyclophosphamide Lenalidomide Carfilzomib

Doxorubicin Pomalidomide Ixazomib

DCEP/D-PACE

METRO28

Carmustine

Bendamustine

Off label: venetoclax

naked antibodie s

Daratumumab (anti-CD38)

Isatuximab (anti-CD38)

Elotuzumab (anti-CS1)

Talquetamab anti-GPRC5d*CD3

Teclistamab anti-BCMA*CD3

Elranatamab anti-BCMA*CD3

idecabtagene vicleucel: anti-BCMA CART

ciltacabtagene autoleucel: anti-BCMA CART

XPO inhibitor

Selinexor

Overall Response Rate (ORR) and Progression Free Survival (PFS) of Recently Approved Therapies in RRMM

T cell redirection therapies

For > 4 LOT and IMID/PI/anti CD38 exposed

Richardson P et al Blood 2014;123(12):1826-32

Siegel DS et al. Blood 2012;120(14): 2817–2825

Lonial S et al. Lancet 2016;387:1551-1560

Chari A et al. N Eng J Med 2019;381:727-738

Touzeau et al EHA 2023

Nooka A et al ASCO 2022;abstract 8007 (oral presentation)

Lesohkin et al Nat Med 2023

Anderson L et al. ASCO 2021;abstract 8016 (poster presentation)

Usmani S et al ASCO 2022;abstract 8028 (poster presentation)

aThis is not a head-to-head comparison and cross-trial comparisons should not be interfered from these data Data represent two populations, PFS includes all patients, DOR includes responding patients only

Pom/Dex Carf/Dex Dara Selinexor Talquetmab Teclistamab Elranatamab Ide-Cel Cilta-Cel

CAR-T cell

therapy:

What is it and how does it work?

CAR-T, chimeric antigen receptor-T cell

• Vein to Vein time (Collection to infusion) 4- 8 weeks

• CART production outright failures –requiring recollection

• CART product out of specification –requires research protocol to administer

• During risk of immune stimulation, patients should be monitored closely (inpatient)

• Brain to Initial Vein time

• Initial referral from primary oncologist

• Consultation appointment at certified CAR-T center

• Insurance Approval (for all non-research CAR-T)

• Patient slot/date allocated to CAR-T site from manufacturer

• T cell harvesting slot aka apheresis slot

Image taken from NIH: National cancer institute. CAR-T cell therap. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/chimeric-antigen-receptor-t-cell-therapy

Importance of Disease Control Prior to CART during Brain to Vein Time

•Both KarMMa3 and CARTIUDE4 studies where patients were randomized to receive CART or conventional therapies showed not everyone benefited from CART due to long “brain to vein time”

•Some patients were never able to get to CART

• this is for a research covered ie “free” CART, likely to be worse with commercial insurance approval requirement

•Some patients progressed prior to CART and these patients had more complications/deaths

• “Curve crossing” in PFS and OS

•In rapidly progressing patients, bispecifics are likely to be more practical

What is a Bispecific Antibody?

• Not patient specific product and are off the shelf products – so could be given by any oncologist

• Currently bispecifics are given in step-up doses (2 to 3 gradually increasing doses) before full dose is given to avoid massive immune stimulation

• However, requires providers to be certified in REMS (Risk Evaluation Mitigation Strategy) program

• REMS programs specify patients should be admitted for 24-48 hours after a given dose of bispecific

• Also, it takes time to get new drugs added to a given centers outpatient formulary – even more challenging to have added to inpatient formulary (due to complexity of inpatient reimbursement)

Factors to Consider in BCMA Sequencing

•If thinking about a BCMA CART, avoid BCMA bispecifics or ADCs until we know more

• note these CARTITUDE -2 prior BCMA pts likely all got bsAb/ADCs on clinical trials at full dose intensity until progression (vs reduced dose intensity or fixed duration, which have shown encouraging data on safety w/o compromise in efficacy)

•to date, loss of BCMA expression rare

*There, are no head-to-head comparisons of these data and naïve comparison should be conducted with caution BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor; EMD, extramedullary disease; HR cytog, high-risk cytogenetics; NA, not available; NR, not reached/not reported; ScFv, single-chain variable fragment; TCR, T-cell receptor; triple-R, triple-class refractory

Berdeja J et al. Lancet 2021;398;314-24; Lin Y et al. EHA 2022;abstract P961 (poster presentation). Cohen et al Blood 2023 . Cohen AD, et al. Blood Adv. 2019;3:2487-2490; Lee H et al Nature Medicine 2023

Adverse Events with CARTs and Bispecifics in RRRM

CAR-T cell therapy: how does it work?

Cytokine Release Syndrome

Timing:

1-2 days (bispecifics, idecel)

7 days ciltacel

Prompt Treatments:

Carry CART/bispecific wallet card

Tylenol

Dexamethasone

Tociluzumab IV – blocks IL6

Anakinra (rarely)

Ensure response (no infections)

Monitor vital signs – have at home:

Thermometer

Blood pressure machine

Pulse oximeter

Adverse Events with CARTs and Bispecifics in RRRM

Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)

•Cause: Cytokines (chemical) or CAR T-cells into central nervous system and cause immune activation

•Onset: With or after CRS

•Suspect if:

– Diminished attention

– Language disturbance

– Impaired handwriting

– Confusion, disorientation

– Agitation

– Aphasia, somnolence

– Tremors, Seizures

– Motor weakness, incontinence

Grading of ICANS: ICE Score

Adverse Events with CARTs and Bispecifics in RRRM

FDA Warning re Ciltacel Secondary Blood Cancers

Based on Phase 1 CARTITUDE 1 Study

• myeloid neoplasms (myelodysplastic syndrome [MDS], acute myeloid leukemia [AML] or MDS followed by AML) occurred in 10% (10/97) of patients following treatment with ciltacel in the CARTITUDE-1 study.

o median time to onset was 485 days (range: 162 to 1040 days) after treatment with ciltacel

o 9/10 patients died following development of myeloid neoplasms.

 4/10 occurred after initiation of subsequent antiMM therapy.

 the10 patients were heavily pre-treated with a median of 7.5 prior therapies (range: 4 to 18). Some of these patients had genetic mutations present prior to ciltacel

 A potential underlying mechanism has not been established.

o Cases of MDS and AML have also been reported in the post marketing setting

Phase 3 CARTITUDE-4 trial: Second primary malignancies after treatment with cilta-cel or standard care

At a median follow-up of 15.9 months

Legend Biotech Announces U.S. FDA Label Update for CARVYKTI® (ciltacabtagene autoleucel; cilta-cel )

Management of Cytopenias

•Depending on severity of low counts, may need up to three times weekly lab monitoring (esp for CART)

•Low white cells/neutrophils – shots like neupogen/Neulasta, preventative antibiotics

•Anemia/Low red cells – transfusion or shots

•Low platelets – transfusions and/or shots (Nplate)

•Rule out other causes-

• B12/folate deficiencies

• viral infections (CMV/EBV/parvovirus B19/hepatitis) – note can get false + HIV after CART

• drugs (Bactrim)

•Consider stem cell infusion ~D30 after CART if stem cells remain

•Consider reducing dose of bispecific if myeloma well controlled

•Consider bone marrow biopsy if counts persistently low and severe

Adverse Events with CARTs and Bispecifics in RRRM

BCMA Bispecifics: IgG Levels, Grade 3- 5 Infections, and Benefit of IVIg

Protective antibody levels (IgG) on BCMA bispecifics go to zero

• Strategies to reduce infections on BCMA bispecifics:

• Vaccinate prior to BCMA bispecific esp COVID

• IVIG support for BCMA bispecifics essential

• Antibiotics prevention for PJP, shingles

• ? less frequent schedule, ? lower maintenance doses, ? fixed duration of therapy (can always retreat later if necc)

• good hand hygiene

New-onset grade ≥3 infections at 1–1.5 years1

Patients switching to Q2W dosing by 1 year

15.6%

Patients remaining on QW dosing at 1 year

Side Effects Related to BCMA Bispecifics

Modifiable with Decreased Frequency and Supportive Care

Kristine A et al, Blood Adv, 2023.

Adverse Events with CARTs and Bispecifics in RRRM

• These on target/off tumor side effects are associated with 20% higher response rates

GPRC5d Toxicities

Treatment of Off-Tumor On Target GPRC5d

Toxicities

Skin Toxicities

Prevention

• emollients (eg urea 10% /ammonium lactate 12% cream)

• sunscreen

Low grade rash

xerostomia

Oral Toxicities

grade ≥3 rashes or refractory to topical therapies

Rashes C2+ or refractory to above

Nail Fragility

• low potency topical corticosteroids

• (e.g. hydrocor, triamcinolone), & escalation to medium potency prn

• short courses of oral steroids (e.g prednisone))

Weight loss

Treatment of oral comorbidities

• hydration (saliva substitutes), or sugar-free chewing gum to stimulate saliva flow.

• sodium lauryl sulfate (SLS) free toothpastes

• regular dental review

• Nutritional supplements

• (eg. thrush or nutritional deficiencies leading to glossitis)

• dermatology consultation

• Nail hardener solution

• Vitamin E oil/emollients

Delaying or reducing dose intensity at time of response is mainstay of managing dysgeusia

Rordiguez-Otero et al. Lancet Oncology in Press. Chari et al ASH 2023

Adverse Events with CARTs and Bispecifics in RRRM

Progressive Parkinson’s-like neurotoxicity after BCMA-directed CAR T

Chief complaint: generalized fatigue on routine visit at 3 months after CART –68-year old treated with anti-BCMA CART in molecular complete remission

Day 100 Neuro

exam :

• mask-like facies

• bradykinesia

• tremor, fatigue

• postural instability

Functional imaging suggests basal ganglia (caudate) origin for neurotoxicity

Conclusions: Practical Aspects of Immunotherapy

• Novel immunotherapies like CAR-Ts and bispecifics require close collaboration between academia and community

• Get evaluated for CART as early as possible and for now, avoid getting a bispecific prior to CART

• However if your disease is incompatible with the “brain to vein” time bispecifics are ready to go

• CARTs cannot be shut off so must be able to tolerate high grade CRS, neurotoxicity; ? older fragile patient, heart failure vs bispecifics can be held

• CRS and ICANs are early side effects that are manageable; Parkinsons is rare but more challenging

• Cytopenias and infections can be more delayed and persistent

• GPRC5d side effects can be modified by changing doses

• We are in a revolutionary era in MM therapy

Acknowledgements: Multiple Myeloma Team at UCSF

Patients and Caregivers

MDs

• Shagun Arora

• Ajai Chari

• Alfred Chung

• Anupama Kumar

• Tom Martin

• Nina Shah

• Peter Sayre

• Jeff Wolf

NPs/PAs

• Helen Diiulio

• Grace Sevilla

• Sam Shenoy (R)

• Nancy Wong

• Laura Zitella

Cellular Therapy Staff

• Jennifer Knoche

• Gabbi Perez

• Cheryl Slagle

RNs

Jennifer Brustein

Lisa Dunn

Katharina Ganapathi

Julie Mccluggage (R)

Jeani Wilmoth (R)

Samanha Zylberman (R)

Social Workers

• Nina Balsamo

• Isabel Curtin

• Rachel Dornhelm

• Judy Smoker

• Ana Zermeño

Dieticians

Medical Assistants

• Nashia Raley

• Joan Viyela

Pharmacists

• Richard Fong

• Mimi Lo

Administrative Staff

Deza Lynn Villanueva

Clinical Research Staff (R)

• Alicia Aschauer

• Mrugakshi Dave

• Edlimar Delgado

• Liam Gima-Lange

• Kenya Gomez

• Jenny Nguyen

• Lauren Nguyen

• Ruixin Sun

• Lena Truong

Translational Research Team

Julia Carnevale

Nupura Kale

Stefanie Bachl

Carter Ching

Justin Eyquem

Chang Liu

Joseph Muldoon

Alexis Talbot

Larry Fong

David Oh

Kai Wu

Arun Wiita

Nikhil Chilakapati

Szu-Ying Chen

Bonell Patiño Escobar

Haley Johnson

Corynn Kasap, Adila Izgutdina

EVALUATION

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Ask – the – Experts Panel

Led by Dr. Joseph Mikhael

Guest Faculty:

Caitlin Costello, MD

Amrita Krishnan, MD

Deborah Doss, RN, OCN

Ajai Chari, MD

EVALUATION

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