IMF Patient & Family Webinar - Back to Basics: From Testing to Tailored Therapy by International Myeloma Foundation

1 Thank you for Joining!

Thank you to our sponsors!

11:10 – 11:25 AM Q&A 11:25 – 11:40 AM BREAK 11:40 – 12:05 PM Managing Myeloma Care

12:05 – 12:20 PM Q&A 12:20 – 12:45 PM Relapse Options: FDA Approved / Clinical Trials Dr.

10:30 – 10:45 AM Q&A 10:45 – 11:10 AM Frontline Options Dr.

IMF Brian G.M. Durie Brian G.M. Durie, International Myeloma Foundation, Studio City, CA Paul Richardson, Dana-Farber Cancer Institute, Boston, MA Mary Steinbach, DNP, APRN, Huntsman Cancer Institute, Salt Lake City, UT Saad Usmani, Memorial Sloan Kettering Cancer Center, New York, NY

Patient and Family Webinar 3 10:00 – 10:05 AM Welcome Announcements with Dr.

10:05 – 10:30 AM Myeloma 101 Back To Basics Dr.

12:45 – 1:00 PM Q&A 1:00PM Webinar Survey and Closing Remarks AGENDA *all times listed in Pacific Time Zone

4 Myeloma 101 Back To Basics Brian G.M. Durie, MD Cedars-Sinai Outpatient Cancer Center Los Angeles, CA IMF Patient and Family Webinar

2 Topics for Today’s Webinar  Back to Basics  Frontline Options  Managing Myeloma Care  Choosing & Sequencing Relapse Therapy

3 Needed Testing !  Routine CBC/CHEM Panel/Urine Testing  SPEP + IFE …Amount/Type of Spike  S FLC ratio … [free light chains]  Bone Marrow/ FISH analysis  X-Rays / Imaging: CT/MRI/PET Scan Myeloma cells as seen in a bone marrow aspirate X-ray image of myeloma lesions in arm

4 More Test Details  Bone marrow FiSH shows chromosome results  MRI and PET/CT show more lesions than x-rays PET PET MRIFISH FiSH – Fluorescent in Situ Hybridization F = Focal D = DiffuseSee: https://www.myeloma.org/videos/imaging-studies-or-scans-should-myeloma-patients-undergo

5 Initial Diagnosis  CRAB: Calcium / Renal / Anemia / Bone  "PRE- CRAB”: BM 60% /sFLC 100 / MRI 2 or more  HR SMM*: BM 20% / sFLC 20/SPEP 2 [and 0.02%] *High Risk MSmolderingultipleMyeloma

6 Response Criteria  PR …. 50% improvement  VGPR …. 75%  CR .... 100% [SPEP zero; BM <5%]  sCR … BM Immuno-Negative / sFLC normal  MRD negative … NGS*/NGF*[10 to -5 or -6] *Next Generation Sequencing and Flow

Managing Myeloma: The Components Supportive Care TransplantTransplantEligiblePatientsIneligiblepatients TherapyInitial Transplant Maintenance Consolidation/ContinuedMaintenance/therapy Reference: Am J.Hematol.2022; 97(8): 1086-1107. doi: 10.1002/ajh.26590 7

Treatment Combinations: New and Old Induction Consolidation Front line treatment consolidationPostMaintenance RescueRelapsed Thal/DexVADDEX ThalidomidePrednisoneNothing NEW DaraRev/DexVDCyBorDVTDVRDKRDIRD+triplet VD/VRDSCT DaratumumabLenalidomideBortezomibIxazomibPomalidomide PomalidomideLenalidomideThalidomideBortezomibCarfilzomibIxazomibDaratumumabIsatuximabElotuzumab OLD SCT Few options 8 CARBelantamabBendamustinePanobinostatSelinexorMafodotinT-Cell  Abecma  TeclistamabMelflufenCarvykti[EMA][EMA]

Current Recommendations  Frontline: TE (transplant eligible) VRd +/- DARA  Frontline: NTE (transplant ineligible) DARA Rd  Relapse: Early and Later  New Agents 9

10 What to Expect with Treatment Myelomaproteinlevel 50%100% 5 years 10 years “biochemical”Firstrelapse UndetectedMRD undetectedPossibleMRD Deep responsefirst responseSecondLaterundetectedfromrelapseMRD

 “Triple therapy”: 3 drug s recommended • Most common = VRD* [Rd for older/frail] (Velcade®/ Revlimid®/ dexamethasone)  ASCT (Autologous Stem Cell Transplant) Can be considered to achieve better response (after 3-6 months of VRd) Zometa®/ Aredia or denosumab for bone lesions Treatment Options 11 Plus * Other options include VCd (CyBorD); KRd; Dara + Rd; Vd

 Triplets or quadruplets in frontline  Maintenance based upon risk  Decisive early relapse treatment (triplets if feasible)  Earlier use of new immune therapies Treatment Strategies in 2022 12

IMF Publications 13Publications available at no-charge: https://www.myeloma.org/publications

IMF Website – http://www.myeloma.org 14

Audience Q&A • Open the Q&A window, allowing you to ask questions to the host and panelists. It will be sent to our moderator and panelists for discussion. • If you have a question that does not get answered today, you can contact our Infoline at 800-452-CURE (2873) US & Canada, 1-818487-7455, or email infoline@myeloma.org.

IMF Patient and Family Webinar 20 Frontline Options Dr. Paul Richardson, Dana-Farber Cancer Institute, Boston, MA

Current and Evolving Standards of Care for the Treatment of Newly Diagnosed Multiple Myeloma Paul G. Richardson, MD RJ Corman Professor of Medicine Harvard Medical School Clinical Program Leader, Director of Clinical Research Jerome Lipper Multiple Myeloma Center Dana-Farber Cancer Institute Boston, Massachusetts

Disclosures • Advisory Committees • Astra Zeneca, Abbvie, Celgene/BMS, Takeda, Oncopeptides, Sanofi, Secura-Bio, Karyopharm, Protocol Intelligence, GSK, Regeneron • Research Funding − Celgene/BMS, Takeda, Oncopeptides, Karyopharm

Treatment For Patients With NDMM TheConsiderationslandscapetreatmentevolvingRecommendedapproachesfortreatmentselection eligibleTransplant-patientsUpfrontordeferredASCT?Tripletorquadrupletinduction?MRD-guidedtherapy ineligibleTransplant-patientsTripletorquadrupletinduction?Specialconsiderationsinelderly/frail/comorbidpatients The generationnext of therapies for basedNovelNDMMimmune-approachesNoveltargetedtherapies Adapted from Richardson PG. 13th Annual IMWG Summit, Vienna, Austria, June 2022.

Treatment For Patients With NDMM TheConsiderationslandscapetreatmentevolvingRecommendedapproachesfortreatmentselection

Treatment Landscape in NDMM Is Evolving... 1. Adapted from Kazandjian D, et al. Br J Haematol 2020;191(5):692–703. 2. Richardson PG. 13th Annual IMWG Summit, Vienna, Austria, June 2022. A, doxorubicin; ASCT, autologous stem cell transplantation; C, cyclophosphamide; CAR, chimeric antigen receptor; d/D, dexamethasone; Dara, daratumumab; Elo, elotuzumab; Isa, isatuximab; Ixa, ixazomib; K, carfilzomib; M, melphalan; mAbs, monoclonal antibodies; MEL200, intravenous melphalan 200 mg/m2; MRD, minimal residual disease; NDMM, newly diagnosed multiple myeloma; P, prednisone (bortezomib in the PAD regimen); PIs, proteasome inhibitors; R, lenalidomide; T, thalidomide; V, bortezomib MRD Positioningearlyemergingassessmentasavitalresearchtool!TimingofASCT~vsdelayedvsotherstrategiesofnext-generationagentsandCARTcelltherapiesintheNDMMsetting2RdVMPMPTVCdVTd RVd (lite)DaraElo-R(V)d-VMPDaraDaraIRd-Rd-VTd Dara-RVd Isa-RVdPADCVdVd Dara-VTd nonTransplant--eligible The Past Lenalidomide- or bortezomib-based Now and in the Future Triplet/quadruplet combinations of R, PIs, mAbs ConsolidationInductionMaintenance Dara-VTd KRd/RVd Dara-IRd Dara-RVd Dara-KRd Ixa (+/- R) Dara-R DaraRV-IRdIsa-KRdRVdDara-KRd Transplant-eligible OptimalMEL200+ASCTRsequencing is the focus of ongoing research1

NDMM: Recommended Regimens 2022 Transplant-eligibleRVdKRd+/-DaraIxa-RdDara-RVd transplantNon-RVd(lite)Dara-RdKRdIxa-RdDara-VMPDara-VCd MaintenanceLenalidomideIxazomibBortezomib • RVd, Dara-VTd • (VTd, VCd) • MEL200+ASCT • Lenalidomide maintenance Transplant-eligible • Dara-Rd, Dara-VMP, RVd, RVd-lite • (VMP, Rd) Non-transplant 1. Callander NS, et al. J Natl Compr Cancer Netw 2022;20(1):8–19. 2. Dimopoulos MA, et al. Ann Oncol 2021;32(3):309–22. NCCN Guidelines1 ESMO Guidelines2 ESMO, European Society for Medical Oncology; NCCN, National Comprehensive Cancer Network.

Considerations for Frontline Therapy • Multiple patient-related and myeloma-related factors can impact treatment outcomes • Strategic considerations for therapy and a long-term view are key1,2 • Immune dysfunction is fundamental to disease pathobiology – and diverse3 • Very high mutational burden, and genetically unstable3 MM is a heterogeneous disease • Younger, transplant-eligible4 / Older, transplant-ineligible5 • Differing preferences • Differing needs • Long-term toxicities important6 NDMM patients are diverse • Real-world considerations7 • Minimizing hospitalization • Sequelae of genotoxic injury and pharmacogenomics in each individual patients, e.g. susceptibility to secondary malignancy, variance in immune reconstitution, impact of CHIP8 Personalizing treatment decision-making is critical Efficacy Patienttreatmentofage Disease stage Disease isotype Frailty Comorbidities/Cytogenetics ImmuneconsiderationsReal-worldfunction 1. Richardson PG, et al. Blood Cancer J 2018;8(11):109. 2. Radivoyevitch T, et al. Leuk Res 2018;74:130. 3. Minnie SA, Hill GR. J Clin Invest 2020;130(4):1565–75. 4. Attal M et al. N Engl J Med 2017;376(14):1311–20. 5. Facon T, et al. Adv Ther 2022;39(5):1976–92. 6. Snowden JA, et al. Br J Haematol 2017;176(6):888–907. 7. Terpos E, et al. Blood Cancer J 2021;11(2):40. 8. Mouhieddine TJ, et al. Nat Commun 2020;11(1):2996. MM is Not One Disease – Tailored Therapy and Real-World Considerations are Essential To Improving Outcome CHIP, clonal hematopoiesis of indeterminate potential; MM, multiple myeloma.

Treatment For Patients With NDMM eligibleTransplant-patientsUpfrontordeferredASCT?Tripletorquadrupletinduction?MRD-guidedtherapy

DETERMINATION Phase 3 Trial: Improved PFS with RVd+ASCT vs RVd-Alone, but No OS Advantage Richardson PG, et al. N Engl J Med 2022;387(2):132–47. *Preliminary data in 198 patients from the start of lenalidomide maintenance DETERMINATION: RVd-alone vs RVd+ASCT, plus lenalidomide maintenance until progression; 28.0% RVd-alone patients received subsequent ASCT Overall Response rates 15.4% 14.8% 37.6% 35.9% 42% 46.8%100806040200 RVd alone (n=357) RVd+ASCT (n=365) (%)Patients PRVGPRCR ORR 95.0% ORR 97.5% PFS – primary endpoint Median 46.2 vs 67.5 months OS – key secondary end point MRD negativity*: 39.8% vs 54.4%, prognostic for PFS

*PFS events: disease progression or death.*TTP events: disease progression. DETERMINATION: PFS, TTP, and EFS Richardson PG, et al. N Engl J Med 2022;387(2):132–47. EFS Median 32.0 vs 47.3 months HR 1.23 *EFS events: receipt of non-protocol therapy, disease progression, or death.

DETERMINATION: Acute Toxicities and SPMs Richardson PG, et al. N Engl J Med 2022;387(2):132–47. *p<0.001. †Includes 1 death related to ASCT on Arm B identified after data cut-off; p=0.12. ‡p=0.002. AE, adverse event; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CLL, chronic lymphocytic leukemia; CML, chronic myelogenous leukemia; MDS, myelodysplastic syndromes; SPMs, second primary malignancies. AE, % (all treatment) RVd-alone (N=357) RVd+ASCT (N=365) Any 78.2 * 94.2 * Any hematologic 60.5 * 89.9 * Any grade 5 (fatal) AE 0.3 1.6 † Neutropenia 42.6 86.3 Thrombocytopenia 19.9 82.7 Leukopenia 19.6 39.7 Anemia 18.2 29.6 Lymphopenia 9.0 10.1 Febrile neutropenia 4.2 9.0 Diarrhea 3.9 4.9 Nausea 0.6 6.6 Mucositis oral 0 5.2 Fatigue 2.8 6.0 Fever 2.0 5.2 Pneumonia 5.0 9.0 Hypophosphatemia 9.5 8.2 Neuropathy 5.6 7.1 SPMs RVd-alone(N=357) RVd+ASCT(N=365) Any, % 10.4 10.7 Any invasive SPM, % 5.3 6.8 Any hematologic SPM, % 2.5 3.6 ALL, n 7 3 AML/MDS, n 0 ‡ 10 ‡ CLL/CML, n 2 0 Any solid tumor SPM, % 3.4 3.3 Any non-invasive solid tumor SPM, % 0 0.5 Any non-melanoma skin cancer, % 5.9 4.1 • All : 9.7% vs 10.8% • Invasive: 4.9% vs 6.5% • Hematologic: 1.59% vs 3.52% 5-year cumulative incidence of SPMs (RVd-alone vs RVd+ASCT):

DETERMINATION: Quality of Life Over Course of Treatment with RVd-Alone vs RVd+ASCT Richardson PG, et al. N Engl J Med 2022;387(2):132–47. EORTC QLQ-C30 Global Health Status EORTC QLQ-C30 Physical Functioning EORTC QLQ-C30 Role Functioning EORTC QLQ-MY20 Side Effects

Triplet or Quadruplet Induction: Novel, Highly Active Regimens with High Rates of MRD Negativity, With or Without ASCT Study ConsolidationInduction/ ASCT MRD-neg PFS OS GMMG-HD61 RVd x 6* Yes NR 3-yr 68.8% 3-yr 89.4% IFM 20092 RVd x 8* No 20.4% 35.0 mos 8-yr 60.2% IFM 20092 RVd x 5* Yes 29.8% 47.3 mos 8-yr 62.2% GRIFFIN3 RVd x 6* Yes 30.1% 3-yr 81.2% NR GMMG-HD74 RVd x 3§ No 35.6% NR NR DETERMINATION5 RVd x 8* No 39.8%† 46.2 mos 5-yr 79.2% FORTE6 KCd x 8‡ Yes 43% 4-yr 51% 4-yr 76% CASSIOPEIA7 Dara-VTd Yes 44% 1.5-yr 85% NR DETERMINATION5 RVd x 5* Yes 54.4%† 67.5 mos 5-yr 80.7% FORTE6 KRd x 12‡ No 56% 4-yr 56% 4-yr 85% FORTE6 KRd x 8‡ Yes 62% 4-yr 69% 4-yr 86% Study ConsolidationInduction/ ASCT MRD-neg PFS OS GMMG-HD61 Elo-RVd x 6* Yes NR 3-yr 67.2% 3-yr 89.7% GMMG-HD74 Isa-RVd x 3§ No 50.1% NR NR IFM 2018-018 Dara-IRd x 6* Yes 51% 2-yr 95.2% NR IFM 2018-049 Dara-KRd x 10* Pre 62% NR NR CONCEPTGMMG-10 Isa-KRd x 6‡ (High-risk MM) No 62.5% 2-yr 75.5% NR CASSIOPEIA7 Dara-VTd Yes 64% 1.5-yr 93% NR GRIFFIN3 Dara-RVd x 6* Yes 64.4% 3-yr 88.9% NR MANHATTAN11 Dara-KRd x 8‡ No 71% 1-yr 98% 1-yr 100% MASTER12 Dara-KRd x ≥4‡ Pre/Post 38%/80% 2-yr 87% 2-yr 94% 1. Goldschmidt H, et al. Blood 2021;138(suppl):abstract 486. 2. Perrot A, et al. Blood 2020;136(suppl):abstract 143. 3. Laubach JP, et al. Blood 2021;136(suppl):abstract 79. 4. Goldschmidt H, et al. Blood 2021;138(suppl):abstract 463. 5. Richardson PG, et al. N Engl J Med 2022;387(2):132–47. 6. Gay F, et al. Lancet Oncol 2021;22(12):1705–20. 7. Moreau P, et al. Lancet 2019;394(10192):29–38. 8. Perrot A, et al. Blood 2021;138(suppl):abstract 464. 9. Touzeau C, et al. J Clin Oncol 2022;40(suppl 16): abstract 8002). 10. Leypoldt LB et al. Leukemia 2022;36(3):885–8. 11. Landgren O, et al. JAMA Oncol 2021;7(6):862–8. 12. Costa LJ, et al. Blood 2021;138(suppl):abstract 481. *3-week cycles. †Preliminary data in 198 patients from start of R maintenance. ‡4-week cycles. §6-week cycles. NR, not reported. Triplets Quadruplets High rates of promisingresponsesMRD-negativeandveryoutcomes Either in conjunction with ASCT or as approachesASCT-sparing Tolerable quadruplet regimens followed by immune therapy-based maintenance MRD-negative rates higher with quadruplet regimens, PFS appears longer

GRIFFIN: Deepened Responses With Dara-RVd+ASCT Over Time Compared With RVd+ASCT 1. Laubach JP, et al. Blood 2021;136(suppl):abstract 79. 2. Voorhees PM et al. Blood. 2020;136(8):936–45. 1009080706050403020100 End consolidationof After 24 maintenancemos End consolidationof After 24 maintenancemos patientsof(%)Percent SD/PD/NE PR VGPR CR sCR D-RVd RVd 66%16% 10%32%31% 14%3%42%39%8%9% 19%8% 14%18%47%13%7%1% 1% PFS in the ITT population for D-RVd versus RVd2ORR at different timepoints2 Safety data • More common AEs included neutropenia, thrombocytopenia, and URI§ • Higher rates of neutropenia and URI did not lead to increased rates of discontinuation for D-RVd versus RVd • Similar rates of any grade and grade 3/4 infections occurred for the DRVd and RVd groups progressionwithoutsurviving% D-RVdRVd 0 100806040200 Months 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 HR, 0.46 (95% CI, 0.21-1.01)2-yearPFSrate PFS3-yearrate 91.6% 88.9% 89.7% 81.2%50 64.4 20.4 30.1 10.6 35.6 2.9 14.6706050403020100 End consolidationof After 24 maintenancemos End consolidationof After 24 maintenancemos patientsof(%)Percent ThresholdThreshold 10 D-RVd RVd 31%10% 13%10-510-6 MRD-neg rate at different timepoints2

Ongoing Phase 3 Studies of Triplets vs Quadruplets in Transplant-Eligible NDMM ClinicalTrials.gov, August 16, 2022 Study ClinicalTrials.gov Regimens Population endpointPrimary completionInitial PERSEUS NCT03710603 Dara-RVd vs RVd Transplant-eligible patients PFS May 2025 IsKia / EMN24 NCT04483739 Isa-KRd vs KRd Transplant-eligible patients rateMRD-negativepost-ASCT July 2025 DSMM XVII NCT03948035 Elo-KRd vs KRd Transplant-eligible patients rateMRD-negative August 2029 Data awaited from ongoing Phase 3 studies of quadruplets vs triplets MRD evaluation key in all studies: Primary endpoint in IsKia and DSMM XVII Secondary endpoint in PERSEUS MRD negativity a key goal of therapy in this setting as a research tool

MANHATTAN: High Response Rates and MRD-Negative Rate With Quadruplet Therapy Alone Landgren O, et al. JAMA Oncol 2021;7(6):862–8. • Patients could then receive ASCT (n=12) or standard-of-care maintenance 41 NDMM patients receivedregimenDara-KRdfor8cycles • No significant differences by age or cytogenetics • At 1 year, 7/8 patients assessed remained MRD-negative MRD-negative rate after 8 cycles: 71% • 1-year PFS 98% • 1-year OS 100% After median follow -up of 11 months: • Common grade 3/4 AEs: 27% neutropenia, 9% rash, 7% lung infection • Dara infusion-related reactions in 40% • Serious AEs in 18% Safety 100 95 711009080706050403020100 ORR CR/VGPR MRD-neg %PATIENTS, Responses after 8 cycles of Dara-KRd N=41

MRD Negativity: Prognostic for Long-Term Benefit Surrogate for PFS, Independent of Treatment 1. Munshi NC, et al. Blood Adv 2020;4(23):5988–99. 2. Avet-Loiseau et al. Clin Lymphoma Myeloma Leuk 2020;20(1):e30–7. 3. Anderson KC, et al. Clin Cancer Res 2021;27(19):5195–212. MRD status a key tool for treatment decision-making, in particular as part of current research

MRD-Adapted Therapeutic Approaches –MIDAS (IFM 2020-02) Perrot A, et al. COMy 2021. https://clinicaltrials.gov/ct2/show/NCT04934475. (6Isa+KRdcycles) InductionMRD Risk-adapted consolidation Maintenance (6Isa+KRdcycles) Lenalidomide – 3 years ASCT (2Isa+KRdandcycles) Lenalidomide – 3 years ASCT Double(2Isa+KRdandcycles)ASCT Isa+iberdomide – 3 years Isa+iberdomide – 3 years Low MRD-risk-negHigh-riskMRD-pos

Treatment For Patients With NDMM ineligibleTransplant-patientsTripletorquadrupletinduction?Specialconsiderationsinelderly/frail/comorbidpatients

Dara-Rd and RVd: Standards of Care for Transplant-Ineligible Patients 1. Facon T, et al. N Engl J Med 2019;380(22):2104–15. 2. San Miguel J, et al. Blood 2022;139(4):492–501. 3. Facon T, et al. Lancet Oncol 2021;22(11):1582–96. 4. Facon T, et al. Adv Ther 2022;39(5):1976–92. 5. Durie BGM, et al. Blood Cancer J 2020;10(5):53. 13.6% 28.2% 31.8% 28.2% 17.1% 12.5% 30.4 12.5100806040200 Dara-Rd (n=368) Rd (n=369) (%)Patients PRVGPRCRsCR ORR 92.9% ORR 81.3% • Durable ≥6 months: 14.9% vs 4.3% • Durable ≥12 months: 10.9% vs 2.4% MRD-negative:2 28.8% vs 9.2% • Median PFS not reached vs 34.4 months (HR 0.53) • Median OS not reached in either arm (HR 0.68) After median follow-up of 56.2 months:3 • Dara-Rd had highest probability of being more effective for PFS and OS Network meta-analysis (vs continuous Rd):4 MAIA1 SWOG S07775 15.3% 25.6% 50.7% 41.1% 24.2% 12.1%100806040200 RVd (n=215) Rd (n=207) (%)Patients PRVGPRCR ORR 90.2% ORR 78.8% • Median PFS 41 vs 29 months (HR 0.74) • Median OS not reached (>84 months) vs 69 months (HR 0.71) • 5-year OS 69% vs 56% After median follow-up of 84 months: • Patients who had not received a transplant: PFS HR 0.74, OS HR 0.63 • Patients with no intent to receive transplant: PFS HR 0.64, OS HR 0.58 • Patients aged <65 / ≥65 years: OS HR 0.64 / 0.77 PFS and OS benefit seen across patient subgroups:

Building on Dara-Rd/RVd Backbones: Ongoing Phase 3 Studies of Triplets vs Quadruplets in the Non-Transplant Setting Study ClinicalTrials.gov Regimens Population endpointPrimary completionInitial CEPHEUS NCT03652064 Dara-RVd vs RVd Transplant-eligible patients without intent for upfront ASCT + transplant-ineligible patients rateMRD-negative 2022September EQUATE NCT04566328 Dara-RVd vs Dara-Rd Transplant-eligible patients without intent for upfront ASCT + transplant-ineligible patients OS 2027December GEM2017FIT NCT03742297 Dara-KRd vs KRd vs VMP-Rd Transplant-ineligible fit patients aged 65–80 years iCR rate October 2023 IMROZ NCT03319667 Isa-RVd vs RVd Transplant-ineligible patients PFS 2022December BENEFIT –IFM2020-05 NCT04751877 Isa-RVd vs Isa-Rd Transplant-ineligible fit patients aged 65–80 years MRD rate at 18 months April 2024 ClinicalTrials.gov, August 16, 2022 iCR, immunophenotypic complete response Addition of daratumumab or isatuximab to RVd, and of bortezomib or carfilzomib to Dara/Isa-Rd under investigation As with studies in transplanteligible patients, MRD negativity a key goal of therapy in this setting Some studies restricted to younger patients without intent for upfront ASCT and/or fit patients

Special Considerations in Elderly / Frail / Comorbid Patients Not able quadrupletstandardtoleratetoregimens May cellunsuitablebeforCARTtherapy Don’t options‘gentler’forgetexistingforthesepatients1 Look quadruplet‘gentler’totherapy • RVd-‘lite’3 • Reduced lenalidomide dose, weekly bortezomib • ORR 86%, ≥VGPR 66% • Median PFS 35.1 months • Well tolerated (4% discontinued for toxicity) • Other variations based on patient age, comorbidities, and functional status – RVdpremium-lite, RVd-ultra-lite4 Reduced-intensity / dose-adjusted regimens,1,2 e.g. • IRd5 (and in FITNess trial6) • Ixa-Dara-dex7 • Rd-R8 • VES-13-adjusted VCd-VTd9 • Start with doublet, add third agent if tolerated Gentler regimens, adjusted by frailty,1,2 e.g. 1. Rajkumar SV. UpToDate. 2022. Topic 6647 Version 73.0. 2. Grant SJ, et al. J Geriatr Oncol 2021;12(4):499–507. 3. O’Donnell EK, et al. Br J Haematol 2018;182(2):222–30. 4. McCaughan GJ, et al. Br J Haematol 2022; doi: 10.1111/bjh.18295. 5. Facon T, et al. Blood 2021;137(26):3616–28. 6. Cook G, et al. Blood 2021;138(suppl):81. 7. Stege CAM, et al. J Clin Oncol 2021;39(25):2758–67. 8. Larocca A, et al. Blood 2021;137(22):3027–36. 9. Nakazato T, et al. Ann Hematol 2021;100(11):2745–54.

probabilitysurvivalfree)(ProgressionTime from start of treatment, months 0 10 20 30 40 1.00.80.60.200.4 RVd-lite: Reduced-Intensity Triplet Regimen with Substantial Efficacy 9 x 35-daycycles:induction • Lenalidomide 15 mg, days 1-21 • Bortezomib 1.3 mg/m2 SC, days 1, 8, 15, 22 • Dex 20 mg days 1, 2, 8, 9, 15, 16, 22, 23 (days 1, 8, 15, 22 only for patients aged >75 years) 6 x 28-daycyclesconsolidation • Lenalidomide 15 mg, days 1-21 • Bortezomib 1.3 mg/m2 SC, days 1, 15 20 22 32 12 0 20 40 60 80 100 N=50 Best response to therapy PR VGPR CR sCR O’Donnell EK, et al. Br J Haematol 2018;182(2):222–30. ORR 86% ≥VGPR 66% Safety and tolerability • Peripheral neuropathy 62% (2% grade 3) • Median treatment duration was 15 cycles (64% completed all 15 cycles) • 2 patients (4%) discontinued due to toxicity Median follow -up 30 months Median PFS 35.1 months Median OS not reached

RVd: Multiple Dose-Adjusted Regimens Regimen Cycle,days Lenalidomide Bortezomib Dexamethasone RVd classic 21 25 mg, days 1–14 SC 1.3 mg/m2, days 1, 4, 8, 11 Days 1, 2, 4, 5, 8, 9, 11, 12 RVd-lite 35 15 mg, days 1–21 SC 1.3 mg/m2, days 1, 8, 15, 22 Days 1, 2, 8, 9, 15, 16, 22, 23 RVd-premium-lite 28 15–25 mg, days 1–21 SC 1.3 mg/m2 (with possible increase to 1.5–1.6 mg/m2), days 1, 8, 15, 22 Days 1, 2, 8, 9, 15, 16, 22, 23 RVd-ultra-lite 28–35 15 mg, days 1–21 SC 1.3 mg/m2, days 1, 8, 15 Days 1, 2, 8, 9, 15, 16 McCaughan GJ, et al. Br J Haematol 2022; doi: Regimen10.1111/bjh.18295selection dependent on patient age, comorbidities, and functional status

Treatment For Patients With NDMMThegenerationnext of therapies for basedNovelNDMMimmune-approachesNoveltargetedtherapies

Selected Emerging Treatment Options for MM 2022: Novel MOAs • Novel mechanisms of action are urgently needed, and are being brought forward into early relapse and NDMM • Emerging role of cellular therapies (CAR T-cell therapies), bispecific antibodies, and more • Continued promise of small molecules and targeted agents (eg, peptide drug conjugates, CELMoDs, venetoclax) • Further development of novel combinations (e.g. with belantamab mafodotin, selinexor, immunoconjugates)RichardsonPG.13thAnnual IMWG Summit, Vienna, Austria, June 2022. Figure adapted from Ramasamy K et al. Blood Rev. 2021;49:100808. CC-92480

BCMA-targeted agents: a 4th treatment pillar for NDMM? Richardson PG. 13th Annual IMWG Summit, Vienna, Austria, June 2022. PomalidomideLenalidomide IMiDs IxazomibCarfilzomibBortezomib PIs IsatuximabDaratumumab mAbs BiTEsBispecificsciltaCARmafodotinBelantamabTs(ide-cel,-cel)/therapiestargetedBCMA-

Belantamab Mafodotin as First-Line Therapy • Belantamab mafodotin + RVd induction/consolidation • ASCT • Belantamab mafodotin + lenalidomide maintenance GEM-BELA-VRd (NCT04802356) • Belantamab mafodotin + KRd • High-risk NCT04822337NDMM • NCT05208307: Belantamab mafodotin plus Pom-dex in high-risk patients • NCT04876248 / NCT05091372: Belantamab mafodotin plus lenalidomide in MRD-positive patients / as MRD-guided maintenance • NCT04680468: Belantamab mafodotin prior to ASCT and with lenalidomide as maintenance Maintenance post-ASCT • Belantamab mafodotin + RVd orDREAMMRd-9 (NCT04091126) • Belantamab mafodotin + Dara-Rd EAE120 (NCT05280275) • Belantamab mafodotin + Rd EAE-2020 (NCT04808037) ClinicalTrials.gov, August 16, 2022 Transplant-eligible patients Transplant-ineligible patients

CAR T Cell Therapies Heading Towards Frontline… CAR T therapycell Study Phase ClinicalTrials.gov Setting endpointPrimary completionInitial Ide-cel KarMMa-2 2 NCT03601078 • Inadequate response to ASCT in 1st line CRORRrate August 2022 KarMMa-4 1 NCT04196491 • High-risk NDMM DLTs, AEs 2023December BMTCTN1902 2 NCT05032820 • Sub-optimal response post ASCT and R maintenance sCR/CR rate at 6 months April 2023 Cilta-cel CARTITUDE-6 3 NCT05257083 • NDMM • Dara-RVd, cilta-cel, R maintenance; Daravs-RVd, ASCT, Dara-RVD, R maintenance MRDSustainedPFS-negCR June 2026 CARTITUDE-2 2 NCT04133636 • Cohort D: <CR post ASCT for NDMM • Cohort E: High-risk NDMM; DaraRVd, cilta-cel, R maintenance • Cohort F: Standard-risk NDMM MRD-neg August 2024 CARTITUDE-5 3 NCT04923893 • Non-transplant NDMM • RVd–cilta-cel vs RVd-Rd PFS June 2026 ClinicalTrials.gov, August 16, 2022

Bispecific Antibodies/T-cell Engagers for Myeloma 1. Shah N, et al. Leukemia 2020;34(4):985–1005. 2. Cohen AD, et al. Clin Cancer Res 2020;26(7):1541–4. Figure reproduced under Creative Commons Attribution 4.0 International License https://www.nature.com/articles/s41375-020-0734-z Bispecific antibody constructs include BiTE® molecules and DuoBody® technology: Both have dual antigen specificity to facilitate cell-to-cell interactions between patients’ T cells and myeloma cells expressing tumorspecific antigens – T cell engagement to BCMA-expressing malignant cells leads to selective MM cell lysis • Bispecific antibodies also referred to as dual-specific antibodies, bifunctional antibodies, or T-cell–engaging antibodies • Target two cell surface molecules at the same time – one on MM cell, one on T cell • Availability is off-the-shelf allowing for immediate treatment • Many different bispecific antibodies are in clinical development (none currently approved in MM): Agent Target Teclistamab BCMA x CD3 Elranatamab BCMA x CD3 Parvurutumab BCMA x CD3 Talquetamab GPRC5D x CD3 Cevostamab FcRH5 x CD3

Bispecific Antibodies/T-cell Engagers in NDMM Agent Target Study Phase ClinicalTrials.gov Setting / Regimen endpointPrimary completionInitial Teclistamab BCMA x CD3 MASTER-2 2 NCT05231629 • MRD-positive post-ASCT • Dara-R vs Dara-teclistamab as consolidation and maintenance MRDSustained-neg April 2026 CR108927 1 NCT04722146 • NDMM • Teclistamab + Dara-RV • Teclistamab + Dara-R DLTsSafety May 2023 MajesTEC-4 3 NCT05243797 • ASCTvsTeclistamab-lenalidomidelenalidomideaspost-maintenance PFS August 2027 Elranatamab BCMA x CD3 MagnetisMM-7 3 NCT05317416 • MRD-positive post-ASCT • Elranatamab vs lenalidomide PFSrateMRD-neg June 2027 Talquetamab GPRC5D x CD3 MonumenTAL-2 1 NCT05050097 • MM* • Talquetamab plus Dara-K / K / Dara-R / R / Pom DLTsSafety August 2023 Cevostamab FcRH5 x CD3 CAMMAGO397751 11 NCT04910568NCT03275103 • RRMM† • RRMM SafetyDLTs December / July 2023 ClinicalTrials.gov, August 16, 2022. *Treatment setting not specified. †Currently only under investigation in RRMM setting.

CELMoDs®: Iberdomide1 and Mezigdomide (CC-92480) 2 1. Lonial S, et al. J Clin Oncol 2019;37(15_suppl):abstract 8006. 2. Richardson PG, et al. Blood 2021;138(suppl 1): abstract 2731. Figures adapted from: (left) Sato T, et al. Front Cell Dev Biol 2021;9:629326; (right) D’Souza C, et al. Front Immunol 2021; 12:632399. Neural stem proliferationcell / CELMoDs / CELMoDs / CELMoDs

Iberdomide in NDMM: A Replacement For Lenalidomide? Study Phase ClinicalTrials.gov Setting / Regimen Primary endpoint Initial completion IFMMIDAS2020-02 3 NCT04934475 • Iberdomide + isatuximab vs lenalidomide + isatuximab as post-ASCT maintenance MRD-neg rate December 2024 CC-220-MM-001 1/2 NCT02773030 • Iberdomide + Vd in NDMM • Iberdomide + Dara-dex in transplantineligible NDMM ORRSafety April 2026 BOREALIS 2 NCT05272826 • Iberdomide +Vd in transplant-ineligible NDMM sCR rate March 2027 EMN26 2 NCT04564703 • Single-agent iberdomide maintenance post-ASCT Improved Tolerabilityefficacy December 2022 KID 1/2 NCT05199311 • Transplant-eligible NDMM • Iberdomide + Kd ORRAEs November 2025 MSKCC 22-040 2 NCT05354557 • Single-agent iberdomide maintenance after suboptimal post-ASCT response CR rate April 2025 University of Nebraska 852-21 2 NCT05177536 • Single-agent iberdomide maintenance post-ASCT 1-year tolerability March 2025 IDEAL 1/2 NCT05392946 • Iberdomide + Dara-Vd in NDMM CRMTDrate May 2027 COMMANDER 1b/2 NCT05434689 • Iberdomide + Dara-dex • Iberdomide + Dara-Kd • MRD-positive patients post-ASCT MRDDLT conversion rate December 2025 ClinicalTrials.gov, August 16, 2022

Novel Targeted Agents for RRMM with Potential Future Application in NDMM • Oral selective XPO1 inhibitor • FDA-approved following 1-3 prior therapies in combination with Vd1 • Phase 2 studies in transplant-ineligible NDMM in combination with Dara-Rd (NCT04782687), Vd/Rd (NCT04717700), and Rd (NCT02343042) • Under investigation with RVd in high-risk NDMM (NCT05422027) • Investigated with high-dose melphalan as conditioning for ASCT (NCT02780609) Selinexor • Novel targeted cytotoxic drug–peptide conjugate mechanism • Granted FDA priority review on August 31, 2020 and approved in March 2021 in RRMM based on HORIZON study2 • Approval provisionally held November 2021, now under review: EMA review complete and full approval recommended June 2022 • Preclinical findings – MM cells exquisitely sensitive to melflufen, including melphalan- and bortezomib-resistant cells3,4 • BMSCs more sensitive to melflufen than melphalan5 Melphalan flufenamide (melflufen) • Potent selective inhibitor of BCL-2 • Specific clinical activity in RRMM patients with t(11;14) (BELLINI);6 phase 3 CANOVA trial ongoing7 • Not currently being investigated in NDMM, but promising preliminary findings in primary PCL, specifically with t(11;14) or BCL2 Venetoclaxoverexpression8 1. Grosicki S, et al. Lancet 2020;396:1563–73. 2. Richardson PG, et al. J Clin Oncol 2021;39(7):757–67. 3. Chauhan D, et al. Clin Cancer Res 2013;19(11):3019–31. 4. Ray A, et al. Br J Haematol 2016;174(3):397–409. 5. Gebraad A, et al. Cells 2022;11(9):1574. 6. Kumar SK, et al. Lancet Oncol 2020;21(12):1630–42. 7. Mateos MV, et al. J Clin Oncol 2020;38(15_suppl):abstract TPS8554. 8. Roy T, et al. Leuk Lymphoma 2022;63(3):759–61. BMSCs, bone marrowderivedstem/stromalmesenchymalcells

• Iberdomide

• Selinexor,

• Quadruplet regimens

New

immuno-therapeutics

• Quadruplets

• Next-generation

/ fit patients • MRD

Next-generation

• BCMA-targeted

Conclusions and Future Directions

with combinations

PIs, IMiDs, and have produced significant improvements in PFS and OS in NDMM are emerging standards of care in transplant-eligible NDMM also under investigation in non-transplant setting, with a focus on younger negativity a key goal of therapy; MRD-adapted therapy emerging – deferred ASCT approach wave of immune therapies: mAbs (including ADCs, bispecifics) represent true new novel mechanisms, as well as other (eg. CAR T cells) standards of care in NDMM? approaches may become a fourth pillar of NDMM treatment small molecules and targeted therapy show great promise CELMoDS® under investigation in NDMM a next-generation replacement for lenalidomide in NDMM? insights to mechanisms of drug action are further expanding treatment/immuno-therapeutic opportunities

mAbs

Academia EMEAFDANCINIH PhilanthropyAdvocacyMMRF/C;IMFIMWG;LLSPharmaceuticalsProgressandHope 15 novel drugs and >30 new FDA-approved drug combos/indications in last 18 years Ongoing MM Collaborative Model for Rapid Translation of Novel Therapeutics From Bench to Bedside 2003–2022 Thank you! Courtesy of Phil McCarthy MD

60 Break

IMF Patient and Family Webinar 61 11:40 – 12:05 PM Managing Myeloma Care Mary Steinbach, DNP, APRN, Huntsman Cancer Institute, Salt Lake City, UT 12:05 – 12:20 PM Q&A 12:20 – 12:45 PM Relapse Options: FDA Approved / Clinical Trials Dr. Saad Usmani, Memorial Sloan Kettering Cancer Center, New York, NY 12:45 – 1:00 PM Q&A 1:00PM Webinar Survey and Closing Remarks AGENDA AFTER BREAK *all times listed in Pacific Time Zone

62 MyelomaManagingCare Mary Steinbach, DNP, APRN, Hunstman Cancer Institute, Salt Lake City, UT IMF Patient and Family Webinar

LIFE IS A CANVAS, YOU ARE THE ARTIST Mary Steinbach, DNP, APRN Huntsman Cancer Institute-University of Utah Patient Education Slides 2022 August 20, 2022

OBJECTIVES COLOR WHEEL OF TREATMENT Myeloma and treatment side effects & symptom management INFECTION PREVENTION and COVID 19 64

GALLERY OF GOALS TREATMENTMYELOMA THERAPIESSUPPORTIVE • Rapid and effective disease control • Durable disease control • Minimize side effects • Allow for good quality of life • Improved overall survival • Prevent disease- and treatmentrelated side effects • Optimize symptom management • Allow for good quality of life DISCUSS GOALS AND PRIORITIES WITH YOUR HEALTHCARE TEAM 65

SHADES OF “AUTO” STEM CELL TRANSPLANT (ASCT) • There are no black and white answers to deciding to undergo a transplant • Undergoing transplant is a commitment for both you and your care partner • Understanding the process will help bring to focus elements needed to decide if/when to undergo transplant ExperienceClinical Data Researchfrom Patient Preference DECISION Adapted from Philippe Moreau, ASH 2015

CAR T: A NEW TREATMENT APPROACH 67

CRSFatigueFeverHeadacheNauseavomiting/ Shortness of Breath DiarrheaWeaknessConfusion CAR T: UNIQUE SIDE EFFECTS CRS = cytokine release syndrome. Oluwole OO, Davila ML. J Leukoc Biol . 2016;100:1265 1272. June CH, et al. Science. 2018;359:1361 1365. Brudno JN, Kochenderfer JN. Blood. 2016;127(26):3321 3330. Brudno JN, Kochenderfer JN. Blood Rev. 2019:34:45 55. Shimabukuro Vornhagen, et al. J Immunother Cancer. 2018;6:56. Lee DW, et al. Biol Blood Marrow Transplant. 2019;25:625 638. CRS IS COMMONA BUT USUALLY MILD SIDE WITHEFFECTCART 68

ConfusionHeadacheAlteredwakefulnessHallucinations Ataxia ApraxiaFacialSeizuresTremorspalsynerveEncephalopathy Neurotoxicity CRS = cytokine release syndrome; ICANS = immune effector cell associated neurotoxicity syndrome; ICE = Immune Effector Cell Encephalopathy screening tool; MRI = magnetic resonance imaging. Brudno JN, Kochenderfer JN. Blood. 2016;127(26):3321 3330. Lee DW, et al. Biol Blood Marrow Transplant. 2019;25:625 638. CAR T: UNIQUE SIDE EFFECTS EFFECTSERIOUSISNEUROTOXICITYARAREBUTSIDEOFCART 69

CARE PARTNER SUPPORT Care partner support is essential for theentire transplant and CAR T processes • Sedated procedures; Education sessions • Assistance with daily activities, managingmedications and alerting the medicalteam of changes • Continued support and assistance isoften needed in the early days afterreturning home. Less assistance will beneeded as time goes on. Care partner can be one person or arotation of many people.

PATIENT-REPORTEDSYMPTOMS Physical • Fatigue • Constipation • Pain • Neuropathy • Impaired FunctioningPhysical • Sexual Dysfunction Psychological • Depression • Anxiety • Sleep Disturbance • Decreased Cognitive Function • Decreased Role & Social Function Financial • Financial burden (80%) • Financial toxicity (43%) A meta-analysis identified the most common patient-reported symptoms and impact on QOL, and were present at all stages of the disease. Symptoms resulted from both myeloma disease and treatment, including transplant, and were in these categories: Ramsenthaler, et al. 2016. https://doi.org/10.1111/ejh.12790. 71

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 THE BRIGHT DARK SIDE TO STEROIDS Steroid Synergy Steroids are a backbone and work in combination to enhance myeloma therapy Steroid Side Effects • Increase in blood sugar levels, diabetes • Weight gain, hair thinning/loss, skin rashes • Irritability, mood swings, depression • crampingweakness,Muscle • Blurred vision, cataracts • Difficulty (insomnia),sleepingfatigue • Flushing/sweating • Stomach bloating, hiccups, heartburn, ulcers, or gas • Increased risk of infections, heart disease • Increase in blood pressure, water retention Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, Abonour R, Siegel DS, Katz M, Greipp PR, Eastern Cooperative Oncology Group (2010) Lenalidomide plus high dose dexamethasone versus lenalidomide plus low dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open label randomised controlled trial. Lancet Oncol 11(1):29 37. King T, Faiman B. Steroid Associated Side Effects: A Symptom Management Update on Multiple Myeloma Treatment  . Clin J Oncol Nurs. 2017 Apr 1;21(2):240 249. doi: 10.1188/17.CJON.240 249. PMID: 28315528. Do not stop or adjust steroid doses without discussing it with your health care provider & 72

Diarrhea may be caused by medications and supplements • Laxatives, antacids with magnesium • Antibiotics, antidepressants, others • Milk thistle, aloe, cayenne, saw palmetto, ginseng • Sugar substitutes in sugar free gum Avoid caffeinated, carbonated, or heavily sugared Takebeveragesanti-diarrheal medication • Imodium®, Lomotil ®, or Colestid if recommended • Fiber binding agents – Metamucil®, Citrucel®, Benefiber® • Welchol ® if recommended Smith LC, et al. CJON.2008;12(3)suppl:37 52. Faiman B. CJON. 2016;20(4):E100 E105. Fluid intake can help with both diarrhea and constipation, and good for kidneys. Discuss GI issues with health care providers to identify causes and make adjustments to medications and supplements. Constipation may be caused by • Opioid pain relievers, antidepressants, heart or blood pressure medications, others • 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® Physical GI SYMPTOMS: PREVENTION & MANAGEMENT 73

Physical Pain can significantly compromise quality of life Sources of pain include bone disease, neuropathy and medical Managementprocedures • Prevent pain when possible • Bone strengtheners to decrease fracture risk; anti viral to prevent shingles; sedation before procedures • Interventions depends on source of pain • Monitor serum calcium levels • Imaging may be needed depending on type and location of pain (eg, MRI, PET-CT) • May include medications (eg bone modifying agents), activity, surgical intervention, radiation therapy, etc • Complementary therapies (Mind-body, medication, yoga, supplements, acupuncture,ANDPAINetc)PREVENTIONMANAGEMENT Faiman B, et al. CJON. 2017;21(5)suppl:19 36. Tell your health care provider about any new bone pain or chronic pain that is notcontrolledadequately 74

Peripheral neuropathy: damage to nerves in extremities (hands, feet, or limbs) • Numbness • Tingling • Prickling sensations • Sensitivity to touch • Burning and/or cold sensation • Muscle weakness Prevention / management: • Bortezomib once-weekly or subcutaneous administration • Massage area with cocoa butter regularly • Supplements: • B complex vitamins (B1, B6, B12) • Folic acid, and/or amino acids but do not take on day of Velcade® (bortezomib) infusion • Safe environment: rugs, furnishings, shoes If PN worsens, your HCP may: • Change your treatment • Prescribe oral or topical pain medication • Suggest physical PERIPHERALtherapyNEUROPATHY MANAGEMENT 75Faiman B, et al. CJON. 2017;21(5)suppl:19 36. Tariman, et al. CJON.2008;12(3)suppl:29 36. Report symptoms of peripheral neuropathy early to your health care provider; nerve damage from PN can be permanent if unaddressed Physical

• Fatigue is the most common reported symptom (98.8%) Sources include anemia, pain, reduced activity, insomnia, treatment toxicity, bone marrow suppression All can affect quality of life and relationships FATIGUE, ANXIETY & DEPRESSION Ramsenthaler, et al. 2016. https://doi.org/10.1111/ejh.12790. Catamero D et al. CJON. 2017; 21(5)suppl:7 18. • Anxiety reported in >35% • Depression nearly 25% Financial concerns, disease progression, end-of-life, and change in social and sexual function were highlighted sources Often, people do not share these symptoms with their provider. Talk to your provider about symptoms that are not well controlled or thoughts of self harm. Help is available. PsychologicalPhysical76

FINANCIAL BURDEN Financial burden comes from • Medical costs • Premiums • Co-payments • Travel expenses • Medical supplies • Prescription costs • Loss of income • Time off work or loss of employment • Caregiver time off work Funding and assistance may be available • Federal programs • Pharmaceutical support • Non-profit organizations • Websites: • Medicare.gov • SSA.gov • LLS.org • Rxassist.org • NeedyMeds.com • HealthWellFoundation.org • Company-specific website Financial Contact the Social Services department at your hospital or clinic to talk to a social worker for assistance. 77

INFECTION PREVENTION AND COVID-19 IN PEOPLE WITH MULTIPLE MYELOMA Patient Education Slides 2021 dysfunctionImmune myelomaMultiple

IMPORTANT WAYS TO SLOW THE SPREAD OF COVID-19 • Get a COVID-19 vaccine (and booster) as soon as you can • Wear a mask (N95 is most protective) that covers your nose and mouth • Stay 6 feet apart from others who don’t live with you • Avoid crowds and poorly ventilated indoor spaces • Test to prevent spread to others • Wash your hands often with soap and water. Use hand sanitizer if soap and water aren’t available CDC = Centers for Disease Control; FDA = Food and Drug Administration. CDC website. Understanding Variants. Accessed January 30, 2022. https://www.cdc.gov/coronavirus/2019-ncov/variants/understanding-variants.html

Person Infected Is Wearing Person InfectedNotIsWearing Nothing Nothing Cloth Mask Surgical Mask N95 Mask (10% leakage) <15 min* min20 min30 2.5hrs Cloth Mask min20 min27 min40 3.3hrs Surgical Mask min30 min40 min60 hrs5 N95 Mask (10% leakage) 2.5hrs 3.3hrs hrs5 25hrs COVID Images: CDC *New research shows that 9.8 feet (3 meters) of social distancing are not enough to ensure protection from Covid-19. Even at that distance, it takes less than five minutes for an unvaccinated person standing in the breath of a person with Covid-19 to become infected with almost 100% certainty. ACGIH website. COVID-19 Fact Sheet: Workers Need Respirators. Accessed January 30, 2022. https://www.acgih.org/covid-19-fact-sheet-worker-resp/ Cornell University website. Cornell Chronicle: Better-fitting masks offer better COVID protection. Accessed January 30, 2022. https://news.cornell.edu/stories/2021/12/better-fitting-masks-offer-better-covid-protection TIME TO INFECTIOUS DOSE FOR SOMEONE NOT INFECTED WITH COVID-19

Manage stress • Rest, relaxation, sleep hygiene • Mental health / social engagement • Complementary therapy Maintain a healthy weight • Nutrition • Activity / Preventativeexercisehealth care • Health screenings, vaccinations • Prevent falls, injury, infection • Stop smoking • Dental care Maintain renal health • Myeloma management • Hydration • Avoid renally-toxic medications – Dose adjust to renal function • Diabetes management Protect your bones • Nutrition, Calcium + D supplement • Weight-bearing activity / walking • Bone strengthening agents 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:66-76. Miceli TS, et al. CJON. 2011;15(4)suppl:9-23. “An ounce of prevention is worth a pound of cure.” Benjamin Franklin 81 HEALTHFUL LIVINGPREVENTIONSTRATEGIES:

KNOWLEDGE IS POWER USE REPUTABLE SOURCES Download or order at myeloma.org Website: http://myeloma.org IMF InfoLine 1 800-452-CURE 9am to 4pm PST MyelomaeNewsletter:MinuteIMFTVTeleconferences 82

YOU ARE NOT ALONE

IMF Patient and Family Webinar 86 Relapse Options: FDA Approved / Clinical Trials Dr. Saad Usmani Memorial Sloan Kettering Cancer Center, New York, NY

Saad Z.

Usmani, MD MBA FACP Chief of Myeloma Service

Choosing and Sequencing Therapy in Relapsed MM.

Disclosures • Research funding: Amgen, Array Biopharma, BMS, Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineDX, Takeda. • Consulting/Advisory Board: Abbvie, Amgen, BMS, Celgene, EdoPharma, Genentech, Gilead, GSK, Janssen, Oncopeptides, Sanofi, Seattle Genetics, SecuraBio, SkylineDX, Takeda, TeneoBio. • Speaker: Amgen, BMS, Janssen, Sanofi. Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

• Discuss current standard of care approach and best practices for treatment of relapsed and/or refractory MM. • Describe MM therapies and considerations for individualizing treatment regimens for relapsed and/or refractory MM. Learning Objectives Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

Approach to Transplant Eligible NDMM ASCT-Eligible Patients Patients with good PS and adequate organ function Standard risk High risk* Dara-VRd ×4-6 cycles1 Consider VRd or KRd ×4-6 cycles2 KRd ×4-6 cycles3 Stem cell mobilization; adequate stem cell harvest (≥10×106 CD34 cells/kg) as per MSK ABMT SOP ASCT Consider consolidation with induction regimen for patients who do not achieve CR or better Lenalidomide maintenance4 IMiD/PI maintenance5,6,7 • ASCT, autologous stem cell transplant; CR, complete response; DVRd, daratumumab, bortezomib, lenalidomide, and dexamethasone; IMiD, immunomodulatory drug; PI, proteasome inhibitor; PS, performance status; Tx, treatment. • *By R ISS staging (R ISS II/III) and/or cytogenetics (t[4;14], t[14;16], or del[17p]), elevated LDH, primary plasma cell leukemia • 1. Attal. NEJM. 2017;376:1311. 2. Voorhees PM. Blood 2020. Gay. ASH 2020. Abstr 294. 4. McCarthy. J Clin Oncol 2017;35:3279. 5. Nooka. Leukemia. 2014;28:690. 6. Dimopoulos. ASH 2018. Abstr 301. 7. Usmani. Lancet Haematol. 2021 Jan;8(1):e45 e54. Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

• DRd, daratumumab, lenalidomide, and dexamethasone; DVd, daratumumab, bortezomib, and dexamethasone; VRd Lite, modified VRd regimen. • Adjust dosing of lenalidomide based on renal function. Consider empiric age adjusted dose reductions for all regimens, as needed 4 • 1. O’Donnell. Br J Haematol. 2018;182:222. 2. Facon. ASH 2018. Abstr LBA 2. 3. Larocca. ASH 2018. Abstr 305. 4.Usmani. Lancet Haematol. 2021 Jan;8(1):e45 e54. Approach to Transplant Ineligible NDMM RVd-Lite1×8 12 cycles DRd2 Consider DVd or VCd or Rd if VRd or DRd is not appropriate (eg, renal failure or other comorbidities) untilLenalidomidemaintenanceprogression3 Continue treatment until progression ASCT-Ineligible Patients Patients with poor PS not related to disease, ejection fraction <50%, pulmonary function test values <50%, concomitant multiorgan amyloidosis IMiD/PI maintenance until progression for high risk4 Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

Factors in Selecting Relapsed Therapy SPM: secondary primary malignancy Patient • Age • Performance status • Renal insufficiency • Poor marrow reserve • Neuropathy • ••ComorbiditiesCardiacdiseaseDiabetes Disease • Risk Status • Cytogenetics • del [17p], t(4;14), t(14;16) • Rapidity of relapse • Rate of rise • Organ damage • Extramedullary disease • Plasma cell leukemia Treatment • Previous therapy • Depth • Duration • Route of administration • Single or combination • Cost • •••ToxicityMyelosuppressionNeuropathyThrombosis • Risk of SPM Dimopoulos MA, et al. Nat Rev Clin Oncol 2015;12(1):42 54; Baz R, et al. Support Care Cancer 2015;23(9):2789 2797; Agarwal A et al. Clin Lymphoma Myeloma Leuk. 2017;17(2):69 77.

Journey to the First Relapse CyBordDRDKRdRVdVTd DaraDaraDaraDara-VTd-RVd-KRd-CyBord RdVd 1stASCTRelapseKRRVR+/-d,+/-d+/-d, V or K alone R+/ d RV +/-d KR +/- d, V or K alone R +/ d V +/ d MAINTENANCEINDUCTION Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani EXPECTED MEDIAN PFS 34-66 moths 40-90 months 24-36 months

Randomized Trials of Lenalidomide-Dex Combinations Trial % WithLenPrior % RefractoryIMiD Relapsed%First- Response Rates for Triplet vs Doublet (%) PFS for Triplet vs Doublet, Months Interim OS for Triplet vs Doublet, Months ASPIRE1 KRd vs Rd 19.8 21 46.5 87 vs 67 26.3 vs 17.6 (P = .0001) 73.3% vs 65% (24 months) TOURMALINE2 IRd vs Rd 12 21 62 78 vs 72 20.6 vs 14.7 (P = .012) ELOQUENT-2 3 Elo-Rd vs Rd 5 47 79 vs 66 19.4 vs 14.9 (P = .014) 43.7 vs 39.6 (P = .026) POLLUX4 Dara-Rd vs Rd 17.5 3.5 50.5 93 vs 76 44.5 vs 17.5 (P<.0001) 65% vs 57% (42-months) K=carfilzomib; P=panobinostat; D=daratumumab; E=elotuzumab; d=dexamethasone 1. Stewart AK, et al. N Engl J Med. 2015;372(2):142 152; 2. Moreau P, et al. N Engl J Med. 2016;374:1621 1634; 3. Lonial S, et al. N Engl J Med. 2015;373(7):621 631; 4. Bahlis NJ, et al. Leukemia 2020 [online ahead of print]. Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

1. Harousseau JL, Attal M. Blood. 2017;130:963 973. 2. Sengsayadeth S, et al. Blood Cancer J. 2017;7(3):e545. 3. Lentzsch S, et al. Oral presentation at: Japanese Society of Hematology 79th Annual Meeting; October 20 22, 2017; Tokyo, Japan; Abstract OS3 12D 2. 4. Facon T, et al. Poster presented at ASH; December 9 12, 2017; Atlanta, GA; Abstract 1824. 5. Moreau P, et al. Leukemia. 2017;31:115 122. 6. Dimopoulos MA, et al. Lancet Oncol. 2016; 17(1):27 38. 7. San Miguel J, et al. Lancet Oncol. 2013;14(11):1055 1066. Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

Trial/Regimen Analysis set N PFS ORR MRD neg. rate at 10-5 CASTOR3 D Vd vs Vd Len refractory at last prior line of therapy D-Vd: n = 45 Vd: n = 60 Median: 9.3 months vs 4.4 months HR: 0.36; 95% CI, 0.21-0.63; P = 0.0002 18 mo PFS rate: 34% vs 2% 81% vs 50% P = 0.0021 9% vs 0% P = 0.0082 ENDEAVOR5,6 Kd vs Vd Len-refractory Kd: n = 113 Vd: n = 122 Median: 8.6 month vs 6.6 months5 HR: 0.80; 95% CI, 0.57 1.116 N/R N/R MM-0037 P low d vs high d Len-refractory P-low d: n = High286d: n = 141 Median: 3.9 months vs 1.9 months HR: 0.50; 95% CI, 0.40 0.62; P <0.0001 30% vs 9% P <0.0001 N/R Len-refractory RRMM len, lenalidomide; D Vd, daratumumab/bortezomid/dexamethasone; Vd, bortezomib/ dexamethasone; PFS, progression free survival; ORR, overall response rate; MRD, minimal residual disease; HR, hazard ratio; CI, confidence interval; Pd, pomalidomide/dexamethasone; Kd, carfilzomib/dexamethasone; N/R, not reported; P, pomalidomide; d, dexamethasone.

Pomalidomide-Dex Based Options Trial regimensPrior % RefractoryLen % RefractoryPI Response Rates for Triplet vs Doublet (%) PFS for Triplet vs Doublet, Months PFS for Len Refractory on Triplet Arm, Months APOLLO1Dara-Pdvs Pd 2 79 48 69 vs 46 12.4 vs 6.9 (P = .0018) 9.9 IsaICARIA-MM2-PdvsPd 3 94 77 60 vs 35 11.5 vs 6.5 (P = .001) -EloNCT026541323-PdvsPd 2 90 78 53 vs 26 10.3 vs 4.7 (P = .008) -VOPTIMISMM4-PdvsPd 2 19 44 61 vs 55 11.99 vs 8.08 (p<0·0001) KPNCT014640345d 6 100 97 50% 7.2 7.2 1. Dimopolus et al Lancet Oncol 2021 2. Attal et al Lancet 2019 3. Dimopolus et al NEJM 2018 4. Jesús F San Miguel et al Lancet Oncol 2014;15: 1195 206 5. Jatin J. Shah et al Blood (2015) 126 (20): 2284–2290. Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

Carfilzomib-Dex Based Options Third Agent % RefractoryLen % RefractoryExposed,PI % CytogeneticsHighWith-Risk Response Rates for Triplet vs Doublet (%) PFS for Triplet vsMonthsDoublet, PFS for RefractoryLenonTripletArm,Months (DaraDaratumumab1-KdvsKdCANDOR) 33 90, 30 15.4 vs 16.9 84 vs 75 28.6 vs 15.2 (P = .0001) 28.1 vs 11 Isatuximab2Isa-KdvsKd(IKEMA) 33 93, 31 24 vs 25 86 vs 83 NR* vs 19.2 (P = .0007) NR* Cyclophosphamide3KCdvsKd 36 100, -- 24 vs 23 78 vs 73 20.7 vs 15.2 (P = .24) 26.2 vs 9.3 1. Dimopolus et al Lancet 2020 2. Martin M et al ASCO 2020 3. Mateos MV et al ASH 2020 *Not reached Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

PFSa,b

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MBA FACP, @szusmani

Phase 3 CANDOR Trial: DKd improved Survival in patients at first Relapse Phase 3 CANDOR study evaluated KdD vs Kd (2:1) in patients with RRMM (N = 466)1 43% of patients in the CANDOR trial had received 1 prior line of therapy1

Patients at first relapse treated with KdD showed an improved PFS and better ORR and MRD responses in comparison with Kd1,2 a Median follow up was ~27 months b Determined by ORCA c MRD negative CR was assessed in the bone marrow using next generation sequencing at a threshold of 1 tumor cell per 10 5 white cells at 12 months (± 4 weeks). d Disease assessments were made per International Myeloma Working Group Uniform Response Criteria. CI, confidence interval; CR, complete response; HR, hazard ratio; Kd, carfilzomib and dexamethasone; KdD, carfilzomib, dexamethasone, and daratumumab; MRD, minimal residual disease; N, number of patients in treatment group; NE, not estimable; ORCA, Onyx Response Computer Algorithm; ORR, overall response rate; PFS, progression free survival; RRMM, relapsed/refractory multiple myeloma. 1 Weisel K, et al. Presented at: European Hematology Association 25th Annual Congress, June 11 21, 2020, Virtual Edition. 2. Dimopoulos M, et al. Poster presented at: 62nd American Society of Hematology Annual Meeting and Exposition, Virtual Meeting; December 5 8, 2020. 1

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Presented by: Saad Z. Usmani, MD

Prior Line2 DKd (n = 312) Kd (n = 154) Events/Patients 52/133 30/67 Median PFS, Months NE 21.3 HR (95% CI) 0.66 (0.42 1.04) ORR and MRD-negative CR rates at first relapsec,d,1 90.2 76.1100604020080 ORR %ORR, (nDKd=133) Kd (n = 67) 16.5 1.520100515 MRD-Negative CR %CR,NegativeMRD (nDKd=133) Kd (n = 67)

IMWG Guidelines： Treatment at Relapse Treatment at first relapse Not refractory to LEN Refractory to LEN DRdPreferredoptions†:orKRd Preferredoptions†: D–Kd, or Isa–Kd, or PVd Vd,notpomalidomidecarfilzomib,isatuximab,DPd,OtherDVdAlternatives‡:orKdoptions:KPd,orIpdIfdaratumumab,orareavailable:VCd,orVMP Treatment after multiple relapses Any first relapse options not yet used (2 new drugs; triplet preferred) Investigational options and clinical trial Alternatives‡: DVd, Kd, DKd, Isa Kd, IRd, Elo Rd, PVd, or SVd (subject to VTd,available:carfilzomibisatuximab,approval)Ifdaratumumab,orarenotRd,Vd,VCd,orVMP Moreau P et al.Lancet Oncol 2021; 22: e105 18 Autologous Stem Cell Transplant Candidate? • SCT not performed as part of frontline therapySCT • Durable remission after 1st SCT (≥24 months on no maintenance therapy, ≥36 months with maintenance therapy) Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

MSKCC Approach to First Relapse Consider Clinical Trials First • Len Naïve or Sensitive / PI Refractory – DRd or KRd • Len Refractory / PI Naïve or Sensitive – DKd or IsaKd • Len and PI Refractory – DPd or IsaPd • Len/Dara Ref / PI Sensitive – KPd or KCyD (PVd as another option) For patients with rapidly advancing, highly symptomatic disease -- consideration for VD-PACE or KD-PACE salvage therapy before considering other options Autologous Stem Cell Transplant Candidate? • SCT not performed as part of frontline therapy • Durable remission after 1st SCT (≥18 months) Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

MSKCC Approach to Second Relapse Consider Clinical Trials First (Expect Majority Are Len/Bor Refractory) • Car Refractory, Pom/Dara sensitive – DPd or IsaPd • Pom Refractory, Car/Dara sensitive – DKd or IsaKd • Car/Dara Refractory, Pom sensitive – EloPd, PomCyD • Pom/Dara Refractory, Car sensitive – KPd, KCyD • T(11;14) – Ven-Dex +/- PI For patients with rapidly advancing, highly symptomatic disease -- consideration for VD-PACE or KD-PACE salvage therapy before considering other options Autologous Stem Cell Transplant Candidate? • SCT not performed as part of frontline therapy • Durable remission after 1st SCT (≥18 months) Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

What is coming down the pike? • Small Molecules – XPO1 inhibitors: Selinexor combinations – CelMods: Iberdomide, CC-480 – BCL2/MCL1 Pathway: Venetoclax and its combinations, several MCL1 inhibitors • Novel Antibody Drug conjugates – Belamaf combinations • Bispecific Antibodies • CARTs Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

CELMoD Iberdomide + Dd or Vd in R/R MM: Phase I/II Study Design • Open-label, dose-escalation/dose-expansion trial Patients with R/R MM and ≥2 prior regimens (≥1 in cohort F), including len/pom and PI) who progressed within 60 days of last therapy Van De Donk. ASH 2020. Abstr 724. Iberdomide 1.0-1.6 mg/day + Daratumumab 16 mg/kg + Dex 40 mg (n = 27) Iberdomide 1.0-1.6 mg/day + Bortezomib 1.3 mg/m2 + Dex 40 mg (n = IberdomideIberdomideIberdomide23)+Dex+Carfilzomib + Dex Phase I: Dose Escalation Dosing schedules Cohort E (28-day cycles) Iberdomide D1 DaratumumabDexamethasone21D1,8,15,22C1-2:D1,8,15,22; C3-6: D1,15; C7+: D1 Cohort F (21 day cycles) Iberdomide D1 BortezomibDexamethasone14D1,8,15C18:D1,4,8,11; C9+: D1,8 BAEFG  Primary endpoints: identify MTD and RP2D, efficacy  Secondary endpoint: safety  RP2D of 1.6 mg/day determined for iberdomide with Dex; cohorts E, F continuing enrollment with 1.6-mg/day dose Cohort D at RP2D Cohort I (post BCMA) at RP2D Cohort J1 (ND MM, ASCT ineligible) Cohort J2 (ND MM, ASCT eligible) Phase II: Dose Expansion

Iberdomide + Dd or Vd in R/R MM: Safety • pulmonary embolism or deep vein thrombosis) reported in either cohort Treatment-Emergent AE, n (%) Iber + Dd (n = 27) All Gr Gr 3 Gr 4 Hematologic  Neutropenia•Febrileneutropenia  Thrombocytopenia  Anemia 19 (70.4) 1 (3.7) 11 (40.7) 10 (37.0) 4 (14.8)0 3 (11.1) 7 (25.9) 14 (51.9) 1 (3.7) 1 (3.7) 1 (3.7) Nonhematologic  Fatigue  Diarrhea  Constipation  Rash  Peripheral neuropathy  Infusion reactionsrelated 9 (33.3) 6 (22.2) 6 (22.2) 32(11.1)(7.4)1(3.7) 0 1 (3.7)0000 000000 Infections  Upper respiratory tract 21 (77.8) 10 (37.0) 3 (11.1)0 2 (7.4)0 Van De Donk. ASH 2020. Abstr 724. Treatment-Emergent AE, n (%) Iber + Vd (n = 23) All Gr Gr 3 Gr 4 Hematologic  Neutropenia•Febrileneutropenia  Thrombocytopenia  Anemia 8 (34.8)0 8 (34.8) 5 (21.7) 5 31(21.7)0(4.3)(13.0) 1 (4.3)0 5 (21.7)0 Nonhematologic  Peripheral neuropathy  Diarrhea  Decreased appetite  Fatigue  Rash  Myalgia  Insomnia  Pruritus  Constipation 7 (30.4) 7 (30.4) 7 (30.4) 6 (26.1) 6 (26.1) 5 (21.7) 5 (21.7) 5 (21.7) 5 (21.7) 0 1 (4.3)00 1 (4.3)0000 000000000 Infections  Upper respiratory tract 14 (60.9) 7 (30.4) 13.08.7 00

Iberdomide + Dd or Vd in R/R MM: Efficacy Best Response, n (%) Iber + Dd (n = 27) Iber + Vd (n = 23) ORR  sCR  CR  VGPR  PR 11 (42.3) 1 (3.8) 2 (7.7) 2 (7.7) 6 (23.1) 14 (60.9)0 1 (4.3) 5 (21.7) 8 (34.8) MR 2 (7.7) 2 (8.7) SD 10 (38.5) 4 (17.4) PD 3 (11.5) 2 (8.7) NE 0 1 (4.3) CBR (MR or better) 13 (50) 16 (69.6) DCR (SD or better) 23 (88.5) 20 (87.0) Median time to response, wks (range) 4.1 (4.0-12.0) 3.6 (3.0-13.1) • High response rates in heavily exposed and highly refractory patient population Among 27 patients in daratumumab 26cohort,were IMiD refractory, 15 daratumumab refractory, 13 triple-class refractory; 4 patient refractory to daratumumab achieved PR – Among 23 patients in bortezomib cohort, 18 were IMiD refractory, 15 PI refractory, 9 bortezomib refractory, 9 triple class refractory; durable responses achieved in patients refractory or with prior exposure to bortezomib • Addition of daratumumab or bortezomib to iberdomide + dexamethasone shows minimal effect on pharmacodynamics Van De Donk. ASH 2020. Abstr 724.

CC-92480 Is a Novel CELMoD Agent Specifically Designed for Rapid Protein Degradation1,2 Efficient substrate degradation leads to apoptosis, potent antiproliferative activity in LEN and POM resistance3 Aiolos degradation efficiency1 1 × 10 6 0.001 1 Compound concentration (µM) (%)Control Ymin = 35 Ymin = 18 Ymin = 5 CC-92480 POM LEN100802004060 Apoptosis induction kinetics LEN resistant cells (H929 1051) 0 50 150100 7.55.02.50induction3Caspase Hr 0.1 µM POM 0.01 µM CC 92480 Antiproliferative activity in LEN/POM resistance 10,0001,0000.010.1110100(nM)IC50Proliferation LEN POM CC-92480 No ResistantParentalcereblon*cellline†cellline‡ CC-92480, a potent CELMoD agent1 LEN1 POM1 *DF15R. †DF15, H929, and OPM 2. ‡H929R1, H929R2, OPM 2R1, OPM 2R2, and OPM 2R3. 1. Hansen. J Med Chem 2020;63:6648. 2. Wong. ASH 2019. Abstr 1815. 3. Richardson. ASCO 2020. Abstract 8500.

CC-92480: Best Response • 7 of 11 patients at RP2D of 1 mg QD 21/28 days were triple-class refractory (to ≥1 IMiD, 1 PI, and 1 anti-CD38 mAb) – Of these patients, 1 had CR, 1 VGPR, 2 PR, and 1 MR Richardson. ASCO 2020. Abstr 8500.

Targeting Apoptosis1-3 1. Roberts AW et al. N Eng J Med 2015;374:311 322. 3.2. Punnoose E et al. Mol Cancer Ther 2016;15:1132 1144 Kumar S et al. Blood. 2017;130:2401 2409. Venetoclax is a selective, orally available small-molecule BCL-2 inhibtor1; active in R/R MM3 Venetoclax (daily dose up to 1,200 mg) has an acceptable safety profile in R/R MM, predominantly in patients with t(11;14) abnormality and favorable BCL 2 family profile In contrast to the CLL experience, TLS appears to be uncommon in MM; ramp-up dosing has not been necessary

• N = 66 patients with R/R MM Venetoclax Is Active Combined With Bortezomib/Dexamethasone …1 1. Moreau P et al. Blood. 2017;130:2392 2400. All(NPatients=66) Nonrefractory(n=37) Nonrefractory(n=22)Refractory(n=28) Refractory(n=42) Prior PIs ORR67%= ORR92%= ORR32%= ORR82%= ORR57%= Prior IMiDs

BELLINI Study: Clinical Response and MRD Rates in Patients With t(11;14)1 110 1. Kumar SK, et al. Lancet Oncol. 2020;21:1630 1642. Clinical Data Cutoff: September 13, 2019. High rates of CR and MRD negativity were observed in the t(11;14) subgroup with VEN+BD.

• N = 42 patients with R/R MM Active With Carfilzomib/Dexamethasone1,a a Data cutoff: September 17, 2018. b One patient died within the first 2 weeks of dosing; no data available. 1. Costa LJ et al. ASH 2018. Abstract 303. All(NPatientsb=42) PI Refractory(n=21) RefractoryDoubleb(n=22)IMiD(nRefractory=26) TargetLevelDose ORR79%= ORR76%= ORR77%= ORR71%= ORR79%= ≥ CR: 38%

Lessons from DREAMM2 Monotherapy

Among pts with grade ≥2 keratopathy (N=60) : Median time to onset of first occurrence was 37 days (range, 19147 days) Median duration of first event was 86.5 days (range, 8-358 days) Most patients (77%) recovered from first occurrencea,b – Decreased visual acuity: 53% all grade, 28% grade 3-4 Best corrected visual acuity change >20/50: 18% Summary

•

Bela-maf: Clinical

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Randomized Phase II Trial (Compared 2.5 mg/kg vs 3.4 mg/kg dosing): 2.5 mg/kg: ORR 32%, median PFS 2.8 months, median DOR 11 months, median OS 13.7 Keratopathy:months71% all grade, 44% grade 3 4

Represents patients with events that recovered either prior to end of tx or after the end of study tx; recovery was defined as any grade 1 exam finding or no exam finding compared with baseline. bLost to follow up (n=4), withdrew (n=4), or died (n=9). After follow up ended for some pts, no more data were available so it is not possible to say if their corneas recovered or not. cBetter than 20/50 at baseline and 20/50 or worse postbaseline. dRecovery was defined as 20/40 or better in the better seeing eye. After follow up ended for some pts, no more data were available, so it is not possible to say if their eyesight recovered or not. 1. Farooq AV, et al. Ophthalmol Ther. 2020;9(4):889 911. 2. Lonial S, et al. Presented at ASH 2020. Abstract #3224.

Phase 2 STORM Trial: Selinexor Plus Dexamethasone1 • PR achieved by two patients who had prior PD following CAR-T cell therapy • 71% of evaluable patients had M protein reductions • Patients with ≥ SD: 78.7% • Median DOR: 4.4 mo • Median PFS: 3.7; OS: 8.6 mo a Previously treated with bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, an alkylating agent, and glucocorticoid, with disease documented to be refractory to ≥1 PI, ≥1 IMiD, daratumumab, a glucocorticoid, and last therapy. ASH 2018. Abstract 598.1. Chari A et al. %Response, Selinexor Dexamethasone+ ORR 26.2 sCR 1.6 VGPR 4.9 PR 19.7 functionadequaterefractorypatientsTreatment-experiencedwithpenta-MMaandorgan (N = 122) R Selinexor 80 mg PO + dexamethasone 20 mg every 2 wk on d 1 and 3 of 28-day cycle Until PD

Phase 3 BOSTON Trial: Selinexor Plus Vd in RRMM No. at Risk SVd 195 187 175 152 135 117 106 89 79 76 69 64 57 51 45 41 35 27 26 22 19 14 9 7 6 4 2 Vd 207 187 175 152 138 127 111 100 90 81 66 59 56 53 49 42 35 26 20 16 10 8 5 4 3 3 2 0.2500.50.751 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 PFSofProbability Time, mo Median PFS, mo SVd 13.93 Vd 9.46 Early and Sustained PFS Benefit (Assessed by IRC) HR = 0.70; P = .0075 30% reduced risk of progression/death with SVd 1.0 Gorsicki S et al. Lancet. 2020;396(10262):1563-1573. Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

Phase 1 study: Selinexor Plus Kd in RRMM Jakubowiak AJ et al. Br J Hematol 2019;186(4):549 560. DL, dose level • Rates of ≥minimal response, ≥PR and VGPR were 71%, 48% and 14%, respectively; • Similar response outcomes were observed for dual-class refractory (PI and IMiDs)/quad-exposed (K, V, R and P) patients (n = 17), and patients refractory to carfilzomib in last line of therapy (n = 13). Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

The Promise of T-cell redirection CAR, chimeric antigen receptor; MM, multiple myeloma CAR T cell therapy is not yet FDA approved for patients with MM. Adapted from Cho S F et al. Front Immunol. 2018;9:1821. BCMAantibodybispecificBCMA Myeloma cell BCMA-bispecificT-cellengager T cell BCMA Myeloma cell T cell CD3toxin Myeloma cell dying - Optimize patient selection, manufacturing, gene transfer, CAR construct, LD approach, AE management, etc. Optimize patient selection, target selection, combinations, AE management, etc.

BCMA Bispecific Antibodies (ASH 2021 Updates) 1. Moreau et al. Abstract #896; 2.Sebag et al. Abstract#895; 3. Kumar et al. Abstract #900; 4. Zonder et al. Abstract #160 (ASH 2021) Teclistamab1 Elranatamab2 TNB-383B3 REGN54584 Schedule Weekly SC Weekly SC or Q2W SC IV q3W Weekly IV Patients 165 55 118 73 Median prior lines 5 6 5 5 Triple Class and Penta Refractory 78% and 30% 91% and NA 61% and NA 89% and 38% Prior BCMA No 22% No No CRS, All (Gr 3/4) 72% (0.6%) 87% (0%) 54% (3%) 38% (0%) ICANS, All (Gr 3/4) 3% (0%) NA 2% (NA) 4% (0%) ORR at higher doses 62% 69% 70% in prior BCMA 60% 75% CR at higher doses 29% Not reported 20% 16%

BCMA CARTs: Summary CARTITUDE-11Cilta-celPhase1/2 CRB-4012Ide-celPhase1 KarMMa3Ide-celPhase2 LUMMICAR-24Zivo-CelPhase1b PRIME5 P-BCMA-101Phase1/2 BCMA+CD19DualGC012F6CAR-T Patients 97 62 128 20 55 19 Median regimensprior 6 6 6 5 8 5 Triple refractory, % 87.6% 69.4% 84.0% 85% 60% 95% CAR-T dose (range0.71×1060.50.95×106) 50, 150, 450 and 800 x 106 150, 300, 450 x106 1.5-1.8/2.5-3.0 x108 0.75-15 x106 1.0-3.0 x105 ORR 97.9% 75.8% 50%/69%/82.0% 94.0% 67%b 94.7% CR/sCR 80.4% 38.7% 25%/29%/39% 28% NR 84.2% PFS 66%@ 18m 8.8m 12m @450mil CRS, all grades 94.8% 75.8% 50%/76%/96% 77%/83%a 17% 95% CRS, grade 3/4 4% 6.5% 0/7%/6% 0% 0% 11% allNeurotoxicity,grades 20.6% 35.5% 0/17%/20% 15%/17%a 3.8% 0% gradeNeurotoxicity,3/4 10.3% 1.6% 0/1%/6% 8%/0a 3.8% 0% a1.5 1.8/2.5 3.0 x108 dose, b0.75x106 dose BCMA, B cell maturation antigen; CAR T, chimeric antigen receptor T cell therapy; CRS, cytokine release syndrome; NR, not reported 1. Usmani et al., ASCO 2021: Abstract 8005; 2. Lin et al., ASH 2020: Abstract 131; 3. Anderson et al., ASCO 2021: Abstract 130; 4. Kumar et al., ASH 2020: Abstract 133; 5. Costello et al., ASH 2020: Abstract 134; 6. Jiang et al., ASCO 2021: Abstract 8014

Phase 1 Study of an Allogeneic Anti-BCMA Therapy for Patients With RRMM: Safety, Efficacy, and Summary 119 a3 patients treated with 320M CART cells and the CA LD regimen are not included. 2 of those responded with 1 patient achieving CR. Mailankody S, et al. ASH 2021. Abstract 651. TEAEs (N=43),Interestofn (%) Grade1 Grade2 Grade3 Grade4 Grade5 GradesAll CRS 13 (30) 10 (23) 1 (2) 0 0 24 (56) Neurotoxicity 4 (9) 2 (5) 0 0 0 6 (14) GvHD 0 0 0 0 0 0 Infection 3 (7) 10 (23) 7 (16) 0 3 (7) 23 (54) IRR to ALLO 647 7(16) 5 (12) 0 0 0 12 (28) Safety  20 (47%) patients had a SAE  30 (70%) patients experienced grade ≥3 neutropenia  Grade 5 infections in 3 patients (2 previously reported; 1 additional due to sepsis)  Use of tocilizumab and steroids: 23% and 14% Efficacy  Median time to response was 16 days  In DL3 FCA expansion, 9 patients with an initial response remain in response with median DOR of 8.3 months ⎯ Of those with a VGPR+, 92% were MRD neg ⎯ MRD neg was correlated with durable response and PFS  sBCMA levels were 10x lower in responders vs nonresponders Response in DL3a FCA39(n=11) FCA60(n=10) FCA90(n=3) FCA(n=24)All ORR, n (%) 7 (64) 8 (80) 2(67) 17 (71) VGPR+, n (%) 5 (46) 5 (50) 1 (33) 11 (46) CR/sCR, n (%) 3 (27) 3 (30) 0 6 (25) Median DOR, months (95% CI) (3.4,8.311.3) (5.6,NENE) (2.4,3.13.1) 8.3 (3.4,11.3) Median follow-up, months (range) (0.5,3.33.8) (3.1,3.811.2) (0.5,3.811.2) Authors’ Conclusions  ALLO 715 with ALLO 647 was well tolerated with low grade CRS, low grade reversible neurotoxicity, no GvHD, and manageable safety  Response rates were comparable to autologous CAR T cell therapy

Weighing Efficacy, Safety & Pace of Disease Relapse will be the key.. (Year)ApprovalRegulatory Route Frequency& onAdministratiof How Quickly Can Patients Get This Modality? (ORRResponseExpected%) Duration Responseof Safety orTransplantSetting,CommunityCenterBoth Cost ConjugateDrugAntibodydirectedBCMA- 2020 IV q 3 weeks until intoleranceprogressionrelapse,or Off the shelf 32% ~12 months (reversible)visualDecreasedKeratopathy,acuity Both ++ AntibodyBispecific ?? 2021 IV or weeklySC,or q 3 weeks progressionrelapse,until or intolerance Off the shelf 65 80% Not reported Low rateCRS,gradelowNT Both ?? AutodirectedBCMACART 2021, 2022 IV once ~3 4 andbetweenweeksapheresisinfusion. 73 98% >9 months CRS/NT Transplant Center ++++ AlloDirectedBCMACART TBD IV once Off the Shelf 60% Not reported CRS/NT Transplant Center ?? Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

CART and Bispecific Trials • Majest-TEC-3: Phase III Study of Teclistamab in Combination With Daratumumab Subcutaneously (SC) (Tec-Dara) Versus Daratumumab SC, Pomalidomide, and Dexamethasone (DPd) or Daratumumab SC, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma (NCT) • KarMMa-3: Phase 3 Study of Ide-cel vs standard regimens in RRMM after 2 – 4 prior lines (NCT03651128) • CARTITUDE-4: Phase 3 Study of Cilta-cel vs DPd or PVd in RRMM after 1 – 3 prior lines (NCT04181827) Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

The Case for Fixed Duration Treatment with Bispecific Antibodies 75 yo RRMM s/p 16 lines, diagnosed in 2001 Line 1: VAD induction, Mel-ASCT, PR Line 2: Thal-Dex, PR Line 3: Bor-Dex, PR Line 4: Len-Dex, PR Line 5: Bor-Dex, PR Line 6: Cyclo-Dex, SD Line 7: CyBorD, SD Line 8: RVd, PR Line 9: RVd-Cy, PR Line 10: Bendamustine-Bor-Dex, SD Line 11: Rd, MR Line 12: Pom-Cy-Dex, SD Line 13: Dara, MR Line 14: Dara-Pom-Dex, PR Line 15: Dara-Pom-Cy-Dex. PR Line 16: BCMA directed BsAb in summer 2019. - Off s/p 8 cycles - Still off therapy, MRD-ve by NGS and flow at 10-5

MSKCC Myeloma Service Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani Alex RRMMLesokhinImmunotherapy TCE, Checkpoints Inhibitors ProfilingMicrobiota,NeoantigensImmune Sham HighCARRRMMMailankodyTrialswithTCells-RiskDisease Malin EpidemiologyAntibodyRRMMHultcrantzTrialsinTCRdrugconjugates Urvi Shah MM Precursor Disease Nutrition & Modifiable Risk EarlyFactorsRelapse Hani Hassoun MM Supportive Care Alliance NDMM/RRMMLiaison Trials Elderly and Frail Neha NDMMKordeClinical Trials Digital SupportiveWearablesCare Carlyn Tan MM Precursor diseases Supportive Care Bone Health High-Risk Disease , Disparities TCE, CAR T DevelopmentalCheckpointCellsInhibitorsTherapeutics Kylee Maclachlan MM Precursor Disease, NDMM ProfilingGenomics,TrialsImmune

MSKCC Myeloma TCT Program Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani Sergio Allo/AutoGiraltHCT for NewMM Regimens CAR T Cells David Chung T Cell exhaustion Auto HCT + Vaccines MM Immunotherapies Michael Scordo HCT PrecisionToxicitiesDrug Dosing CAR T Cells Gunjan Shah HCT PrecisionToxicitiesDrug Dosing CAR T SalvageCellsAuto and Allo HCT Heather AutoNovelPrecisionHomeboundHCTAmyloidosisLandauToxicitiesHCTDrugDosingRegimensforSalvage Oscar Lahoud Auto HCT and CAR T Cells Post HCT Therapies Saad Z. Usmani High-Risk Disease Biology/Trials CAR T Cells Auto HCT for MM

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130 IMF Patient and Family Webinar