Myeloma 101 & Understanding Your Labs
Joseph Mikhael, MD, MEd, FRCPC, FACP
Chief Medical Officer, International Myeloma Foundation Teresa Miceli, RN, BSN, OCN
International Myeloma Foundation Nurse Leadership Board Member
Q&A with Teresa and Dr. Joe: Understanding Myeloma Basics
Joseph Mikhael, MD, MEd, FRCPC, FACP
Professor, Applied Cancer Research and Drug Discovery, Translational Genomics Research Institute (TGen), City of Hope Cancer Center
Chief Medical Officer, International Myeloma Foundation
Consultant Hematologist and Director, Myeloma Research, Phase 1 Program, HonorHealth Research Institute
Adjunct Professor, College of Health Solutions, Arizona State University
Teresa S. Miceli RN BSN OCN
Mayo Clinic, Rochester, MN
• Mayo Associate
• Assistant Professor of Nursing
• Myeloma Research RN Navigator
International Myeloma Foundation
• InfoLine Advisor
• Nurse Leadership Board
• Support Group Leader
NCI Myeloma Steering Committee
How
Rate of New Cases per 100,000 Persons by Race/Ethnicity & Sex
How common is Myeloma?
Percent of New Cases by Age
https://seer.cancer.gov/statfacts/html/mulmy.html; dated 6.15.2024
What
Biochemical or Symptomatic Progression/Relapse
Causes Myeloma? How/Why Did I Get This?
Environmental Factors:
• Exposure to some chemicals
• Radiation exposure
Examples:
Agent Orange
Burn pits
Pesticides, Herbicides
Firefighter/First Responder exposures
Individual Factors:
• Age
• Family History of related disorders
• Personal History of MGUS or SMM
• Obesity
In most cases, the honest truth
WE DON’T KNOW
Bone Marrow Cells – Good & Bad
Hematopoietic stem cell
White Blood cell
Platelets
Red Blood Cells
Plasma cell
Photo Credit
Clonal Plasma cells
(Mono)clonal Plasma Cells
Heavy Chain: G, A, M, D, E
Heavy Chain = M-Spike
Clonal Plasma cells 65% IgG – most common 20% IgA – associated with AL Amyloid 5% to 10% light chain-only (kappa, lambda) Less common: IgD, IgE, IgM eGFR = estimated glomerular filtration rate; M-spike = monoclonal spike; Ig = Immunoglobulin
Spectrum of Monoclonal Protein Disorders
• AL-Amyloid
• POEMS
• Light or Heavy Chain Deposition Disease
• MGRS = Renal
• MGNS = Neuro
Condition MGUS1-4 (Monoclonal Gammopathy of Undetermined Significance) SMM1-5,8 (Smoldering Multiple Myeloma) Active Multiple Myeloma6-8
Clonal plasma cells in bone marrow <10% 10%-60% >10%
Presence of Myeloma
Defining Events None None Yes
Likelihood of progression ~1% per year ~10% per year Not Applicable
Treatment No; observation Yes for high risk*; No for others Yes
* In clinical trial
1. Kyle RA, et al. N Engl J Med. 2007;356:2582-90.
2. IMWG. Br J Haematol. 2003;121:749-57.
3. Jagannath S, et al. Clin Lymphoma Myeloma Leuk. 2010;10(1):28-43.
5. Mateos M-V, et al. Blood. 2009;114:Abstract 614.
6. Durie BG, Salmon SE. Cancer. 1975;36:842-854.
7. Durie BG, et al. Leukemia. 2006;20(9):1467-1473.
8. Rajkumar SV, et al. Lancet Oncology 2014; 15:e538-e548.
4. Kyle RA, et al. Curr Hematol Malig Rep. 2010;5(2):62-69.
Multiple Myeloma and Myeloma Defining Events
Testing For Myeloma: Blood & Urine
Test Name
CBC + differential
Complete metabolic panel
Beta-2 Microglobulin (B2M)
Lactate Dehydrogenase (LDH)
Serum Immunofixation and Protein electrophoresis (SPEP+IFE)
Immunoglobulins (G, A, M, D, E)
Free light chain assay with kappa/lambda ratio
Urine immunofixation & protein electrophoresis (UPEP+IFE)
What it means
Hemoglobin, WBC, Platelets
Creatinine, Calcium, Albumin, Liver function
Part of staging and risk stratification
Measures the level of normal and clonal protein Identifies the type of clonal protein
Measures the level of normal and clonal protein Identifies the type of clonal protein
This Photo by Unknown Author is licensed under CC BY-SA-NC
Testing For Myeloma: Imaging
Imaging:
– Skeletal survey: Series of X-rays; less sensitive than other techniques
– Whole body low dose (CTWB-LD CT )
– Positron Emission Tomography (PET/CT)
– Magnetic Resonance Imaging (MRI)
Healthy bone versus myeloma bone disease
This Photo by Unknown Author is licensed
Testing For Myeloma: Bone Marrow
Bone marrow genetics
• Cytogenetics
• Fluorescence in situ hybridization (FISH)
• Next generation sequencing (NGS)
This Photo by Unknown Author is licensed under CC BY-SA
Staging and Risk Stratification
International Staging System (ISS) (only β2M and albumin)
Result 1 β2M < 3.5 mg/L; serum albumin ≥ 3.5 g/dL
2 β2M < 3.5 mg/L; serum albumin < 3.5 g/dL; or β2M 3.5 to 5.5 mg/L, irrespective of serum albumin 3 β2M > 5.5 mg/L Revised International Staging System (R-ISS), adding LDH & FISH
High Risk FISH Results*
Not R-ISS stage I or III
Myeloma Treatment Schema
Transplant
Eligible Patients
Initial Therap y Transplant (ASCT) Maintenanc e Treatmen t of Relapsed disease
Transplant Ineligible Patients Consolidation / Maintenance Continued therapy Everyone Supportive Care
HCP Clinical Experience Research Results Your Preference TREATMENT DECISION
Philippe Moreau. ASH 2015.
Drug Class Overview
IMiD
immunomodulatory drug
Proteasome inhibitor
Thalomid (thalidomide) T or Thal
Revlimid (lenalidomide) R, Rev, Len Pomalyst (pomalidomide) P or Pom
Drug Class Overview
Peptide Drug Conjugate*
BCMA Targeted Antibody Drug
Conjugate (ADC)*
Bispecific Antibodies
Pipeline
Pepaxto (Melphalan Flufenamide)
Blenrep (belantamab mafodotin-blmf)
Abecma (idecabtagene vicleucel)
Carvykti (ciltacabtagene vicleucel)
Tecvayli (teclistimab)
Talvey (Talquetamab)
Elrexfio (Elranatamab)
Bela, Belamaf, or B
Cilta-cel
Tec
Talq Elra
Cevostamab, Iberdomide, Mezigdomide, Venetoclax
Linvoseltamab, LCAR-B38M, ABBV-383 ……………………………
Measuring Disease Response: IMWG Response Criteria
Negative by next generation flow (NGF) (minimum sensitivity 1 in 10-5 nucleated cells or higher)*
mCR AND normal Free Light Chain ratio, Bone Marrow negative by flow,
2 measures
CR AND negative PCR
Complete Response: Negative immunofixation (IFE); no more than 5% plasma cells in BM; 2 measures
Very Good Partial Response: 90% reduction in myeloma protein
Partial Response: at least 50% reduction in myeloma protein
Minimal Response
Stable Disease: Not meeting above criteria
Progressive Disease: At least 25% increase in identified myeloma protein from lowest level
MRD = Minimal Residual Disease
sCR = Stringent Complete Response; BM = Bone Marrow
Kumar, S., Paiva, B., Anderson, K. C., Durie, B., Landgren, O., Moreau, P., ... & Dimopoulos, M. (2016). International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. The lancet oncology, 17(8), e328-e346.
When Do I Need A New Treatment?
Biochemical or Symptomatic Progression/Relapse
• Not every relapse requires immediate therapy
• Each case is different
Asymptomatic biochemical relapse on 2 consecutive assessments
Consider Treatment
Symptomatic or extramedullary disease
Asymptomatic high-risk disease or rapid doubling time or extensive marrow involvement Consider Observation Monitor Carefully
Initiate Treatment
Patient-/Disease-Specific Monitor Carefully
Targets on the Myeloma Cell Surface and Therapeutic Antibodies
Bi-Specific Antibodies
Talquetamab
Antibody Drug Elotuzumab
Bi-Specific Antibodies
Bi-Specific Antibodies
Antibody Drug
Immune Therapies
Ide-cel CAR-T
Cilta-cel CAR-T
Other Bi-Specific Antibodies
The Evolution of Myeloma Therapy
VD
Rev/Dex
CyBorD
VTD
VRD
KRD
D-VMP
DRD
Tandem ASCT (?)
Nothing
Thalidomide?
Bortezomib
Ixazomib
Lenalidomide
Combinations
D-VRD
Isa-VRD
D-KRD
Isa-VRD “More” induction?
Daratumumab?
Carfilzomib?
Lenalidomide + PI
ASCT, autologous stem cell transplant; CAR, chimeric antigen receptor; Cy, cyclophosphamide; d- daratumumab; D/dex, dexamethasone; isa, isatuximab; K, carfilzomib; M, melphalan; PD-L1, programmed death ligand-1; PI, proteasome inhibitor; Rev, lenalidomide; V, bortezomib.
Bortezomib
Lenalidomide
Carfilzomib
Pomalidomide
Selinexor
Panobinostat
Daratumumab
Ixazomib
Elotuzumab
Isatuximab
Belantamab mafodotin*
Melphalan flufenamide*
Idecabtagene autoleucel
Ciltacabtagene autoleucel
Teclistamab, Talquetamab
Elranatamab
CAR T Cell Therapy
Bispecific/Tri-specific Antibodies
Cell Modifying Agents
Venetoclax*
PD/PDL-1 Inhibition?
Small Molecules
Speaker’s own opinions.
* These agents are currently off the market but available through special programs
What about Disease Control and Cure in Myeloma?
Biochemical or Symptomatic Progression/Relapse
Defining “Cure” has many considerations:
Minimal Residual Disease Negative (MRD-)
Time Off Therapy
Functional Cure
Unmeasurable Disease, Receiving No Treatment Active Disease Requiring Treatment Stable or Unmeasurable Disease, Receiving Treatment Control is the immediate priority with active disease Cure remains the overall goal
https://seer.cancer.gov/statfacts/html/mulmy.html;
