SGLS 2025 Friday Slides

Welcome!

Robin Tuohy,

IMF Vice President,

Patient Support

25-Year Care Partner | Advocate | Support Group Leader

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IN-PERSON PROGRAM | JULY 17 – 20, 2025 Omni Viking Lakes - Minneapolis, MN

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Friday Morning Agenda

Key Questions in Myeloma Research:

How the IMF is Addressing Them

Joseph Mikhael, MD, MEd, FRCPC, FACP, FASCO

IMF Chief Medical Officer, SAB & IMWG

WE ARE LIVING IN THE GOLDEN AGE OF MYELOMA WITH IMPROVING QUANTITY AND QUALITY OF LIFE!

BUT WE ARE ALSO LIVING IN A DAY OF UNPRECEDENTED

DISPARITIES IN MYELOMA WORLDWIDE...

RESEARCH IS ESSENTIALLY BASED ON

ANSWERING IMPORTANT QUESTIONS

I will describe the “state” of myeloma research by proposing 10 critical unanswered questions in myeloma

Black Swan Research Initiative

• Black Swan events refers to unpredictable events that have significant impact which are often criticized before and then post hoc rationalized as something that was predictable.

• When we started BSRI over ten years ago, the three interrelated “black swan” ideas we put out were:

• Myeloma was curable if treated in the early asymptomatic stage

• Myeloma was curable if we can get to sustained MRD negative status with treatment.

• Sustained MRD negative status was an indicator of cure

Black Swan Research Initiative

To accomplish the goals of BSRI we needed:

• A cure trial targeting high risk SMM (ASCENT)

• Widely available MRD test development (NGF, Peripheral blood MRD)

• MRD surrogacy studies (I2TEAMM)

• Screening and Early detection studies

Black Swan Research Initiative

Current and Future BSRI goals (for funding, for grants, IMWG guidelines and research projects)

1. MRD as a surrogate endpoint for full regulatory approval in myeloma trials

2. Improved MRD testing (deeper; peripheral blood, etc)

3. Successor cure trials (ASCENT 2, and more)

4. Early Detection

1. SHOULD WE BE SCREENING FOR MYELOMA?

Iceland Screens, Treats, or Prevents Multiple Myeloma

Control arm

Inclusion criteria:

-Born ≤1975

-Icelandic resident

Exclusion criteria:

-Previous lymphoproliferative disease

Only arm 2 and 3:

-Previously known MGUS (excluded for this analysis)

Psychiatric health: Assessed at registration, after MGUS notification, and annually

Intervention arm

Rögnvaldsson S et al. (2021) Blood Cancer Journal; 11, 94

Dr. Joe’s Take on Screening

This is a MASSIVE and critical study to educate us about the feasibility and usefulness of screening

We have to remember Iceland does not represent the whole planet but is an important place to start (especially due to genetic information there)

All screening programs are focused by age, gender, family history, etc and we should expect the same in MM – especially as it is twice as common in patients of African descent

The ISTOPMM trial will likely answer the key question of whether or not screening saves lives in the next 2 years...

IMF Role – We are involved in iSTOPMM and the CHAAMP study in Charlotte – this is part of the Black Swan Research Initiative

2. SHOULD WE TREAT SMOLDERING MYELOMA?

AQUILA: Study Design

AQUILA

Screening

Key eligibility criteria:

• ≥18 years of age

• Confirmed SMM diagnosis (per IMWG criteria) for ≤5 years

• ECOG PS score of 0 or 1

• Clonal BMPCs ≥10% and ≥1 of the following risk factors:

- Serum M-protein ≥30 g/L

- IgA SMM

- Immunoparesis with reduction of 2 uninvolved Ig isotypes

- Serum involved:uninvolved FLC ratio ≥8 and <100

- Clonal BMPCs >50% to <60%

All patients were required to have CT/PET-CT and MRI imaging during screening

enrollment period: December 2017 to May 2019 at 124 sites in 23 countries

Treatment/active monitoring phase Follow-up phase

DARA monotherapy

1800 mg SCb QW Cycles 1-2, Q2W Cycles 3-6, Q4W thereafter in 28-day cycles until 39 cycles/36 months*

Active monitoring

No disease-specific treatment, with AE monitoring up to 36 months*

• Efficacy follow-up until progression by SLiM-CRAB

• Survival follow-up every 6 months until end of study

Primary endpoint:

• PFS by IRC per IMWG SLiM-CRAB criteriac

Key secondary endpoints:

• ORR

• Time to first-line treatment for MM

• PFS on first-line treatment for MM

• Overall survival

*Or confirmed disease progression (whichever occurred first).

Stratified by number of risk factorsa for progression to MM (<3 vs ≥3)

Disease evaluation schedule

• Laboratory efficacy – Every 12 weeks by central lab until disease progression

• Imaging (CT/PET-CT, MRI) – Yearly (central review)

• Bone marrow – At least every 2 years

IMWG, International Myeloma Working Group; ECOG PS, Eastern Cooperative Oncology Group performance status; BMPC, bone marrow plasma cell; FLC, free light chain; CT, computed tomography; MRI, magnetic resonance imaging; QW, weekly; Q2W, every 2 weeks; Q4W, every 4 weeks; AE, adverse event; IRC, independent review committee; ORR, overall response rate. aRisk factors included involved:uninvolved FLC ratio ≥8 (yes vs no), serum Mprotein ≥30 g/L (yes vs no), IgA SMM (yes vs no), immunoparesis (reduction of 2 uninvolved immunoglobulins vs other), or clonal BMPCs (>50% to <60% vs ≤50%). bDARA SC (1800 mg co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; 2,000 U/mL; ENHANZE® drug delivery technology; Halozyme, Inc.]). cPFS was defined as duration from randomization to initial documented progression to active MM or death due to any cause, whichever occurred first. 22

AQUILA: Progression to MM by IMWG SLiM-CRAB Criteria (IRC Assessment)

AQUILA: Overall Survival

*Deaths due to an event occurring after the AE reporting window (ie, events that happened after patient started subsequent therapy or >30 days after last dose) or deaths with unknown reason.

Early intervention with fixed duration DARA extended overall survival versus active monitoring

AQUILA: Safety Overview

Dr. Joe’s Take on Smoldering Myeloma

• Wow this is a VERY important study and may well change the way we think about and treat high risk smoldering myeloma

• The study was critical to really prove we can delay the progression to active myeloma and even improve survival with 3 years of daratumumab

• It underscores the important of a DISCUSSION with the health care team as many options can be offered to patients with high risk smoldering MM

• There will me MANY more trials coming in this area, with even more intense therapies like combinations and even CAR T Cell therapy...

• IMF Role – We have conducted the ASCENT and CESAR trials and are planning the ASCENT 2 trial – intensely treating high risk SMM

3. IS IT QUADRUPLETS FOR ALL IN

FRONTLINE MYELOMA?

PERSEUS: Study Design

Induction

• Transplanteligible NDMM

• Age 18-70 years

• ECOG PS ≤2

V: 1.3 mg/m2 SC

Days 1, 4, 8, 11

R: 25 mg PO Days 1-21

d: 40 mg PO/IV Days 1-4, 9-12

: 1,800 mg SCb

Cycles 1-2 Q2W Cycles 3-4

VRd administered as in the VRd group

Consolidation

V: 1.3 mg/m2 SC Days 1, 4, 8, 11

: 25 mg PO Days 1-21

DARA: 1,800 mg SCb Q2W

VRd administered as in the VRd group

Maintenance

DARA: 1,800 mg SCb Q4W R: 10 mg PO Days 1-28

Primary endpoint: PFSc

Key secondary endpoints: Overall ≥CR rate,c overall MRD-negativity rate,d OS

Discontinue DARA therapy only

Discontinue DARA therapy only after ≥ 24 months of D-R maintenance for patients with ≥CR and 12 months of sustained MRD negativity

Restart DARA therapy upon confirmed loss of CR without PD or recurrence of MRD

ECOG PS, Eastern Cooperative Oncology Group performance status; V, bortezomib; SC, subcutaneous; PO, oral; d, dexamethasone; IV, intravenous; QW, weekly; Q2W, every 2 weeks; PD, progressive disease; Q4W, every 4 weeks; MRD, minimal residual disease; CR, complete response; OS, overall survival; ISS, International Staging System; rHuPH20, recombinant human hyaluronidase PH20; IMWG, International Myeloma Working Group; VGPR, very good partial response. aStratified by ISS stage and cytogenetic risk. bDARA 1,800 mg co-formulated with rHuPH20 (2,000 U/mL; ENHANZE drug delivery technology, Halozyme, Inc., San Diego, CA, USA). cResponse and disease progression were assessed using a computerized algorithm based on IMWG response criteria. dMRD was assessed using the clonoSEQ assay (v.2.0; Adaptive Biotechnologies, Seattle, WA, USA) in patients with ≥VGPR post consolidation and at the time of suspected ≥CR. Overall MRD-negativity rate was defined as the proportion of patients who achieved both MRD negativity (10–5 threshold) and ≥CR at any time.

Isa-VRD vs VRD: Study design – Part 1

Stratification for randomization prior to:

1. Induction: R-ISS stage (I/II versus III versus not classified)

Treatment for 3 years or until PD Cycles 4+ Isa: 10 mg/kg IV Cycle 1 Cycles 2-3

1

2-3 R: 10/15/25 mg PO; Days 1-14 and 22-35

V: 1.3 mg/m2 SC; Days 1, 4, 8, 11, 22, 25, 29, and 32

d: 20 mg POb; Days 1-2, 4-5, 8-9, 11-12, 15, 22-23, 25-26, 29-30, and 32-33

R: 10 mg (up to 15 mg, if tolerated) PO; continuously

d: 20 mg PO; Days 1, 8, 15, and 22

2. Maintenance: R-ISS stage at study entry (I/II versus III versus not classified) and MRD– after last HDM (no versus yes versus unknown) Induction (3 x 6-week cycles) Maintenance (4-week cycles) Days 1, 8, 15, and 22 Days 1 and 15 Day 1 Days 1, 8, 15, 22, and 29 Days 1, 15, 29

Primary end pointsc: Post-induction MRD– (NGF, 10–5); PFS after second randomization

Key secondary end points: PFS (whole study); OS (whole study and from second randomization); post-induction CR; CR and MRD– after HDM and during and after maintenance therapy

Selected secondary end point: PFS after first randomization

Study design: Isa-VRd vs VRd in transplant-ineligible NDMM

Treatment until PD, unacceptable toxicities, patient withdrawal

Primary endpoint: PFS

Key secondary endpoints: CR rate, MRD– CR (NGS, 10-5) rate, ≥VGPR rate, OS

*Patients considered Ti due to age or comorbidities.

†In the continuous phase, patients randomized to the VRd arm who experience PD may cross over to receive Isa-Rd.

‡10 mg/day if eGFR 30–<60 mL/min/1.73 m2.

§If aged ≥75 years, d was administered on days 1, 4, 8, 11, 15, 22, 25, 29, and 32.

BY: Thierry Facon, MD

CEPHEUS: Phase 3 Study of DARA SC-VRd Versus VRd

in TIE or Transplant-deferred Patients With NDMM

Key eligibility criteria:

• NDMM (TIE or transplant deferred)

• ECOG PS score of 0-2

• Frailty score of 0-1

V: 1.3 mg/m2 SC Days 1, 4, 8, 11

: 25 mg PO Days 1-14

: 20 mg PO Days 1, 2, 4, 5, 8, 9, 11, 12

DARA: 1,800 mg SC QW Cycles 1-2, Q3W Cycles 3-8 VRd: schedule as above

21-day cycles

8 cycles of bortezomib treatment

Cycle 9+ R: 25 mg PO Days 1-21

: 40 mg PO Days 1, 8, 15, 22

Primary endpoint:

• Overall MRD (≥CR) negativity

DARA: 1,800 mg SC Q4W Rd: schedule as above 28-day cycles until disease progression or unacceptable toxicity

Key secondary endpoints:

• PFS

• Sustained MRD (≥CR) negativity (≥12 months)

• ≥CR rate

• OS

SC, daratumumab and recombinant human hyaluronidase for subcutaneous injection; ECOG PS, Eastern Cooperative Oncology Group performance status; V, bortezomib; SC, subcutaneous; R, lenalidomide; PO, oral; d,

Dr. Joe’s Take on Quadruplets

• It is very clear that combining more mechanisms of action controls the disease better

• With these newer agents, it is feasible to give quadruplets to most patients with newly diagnosed myeloma

• There is an art in dosing these agents to maximize the synergy and minimize the toxicity

• dose of lenalidomide

• dose and frequency of bortezomib

• dosing and tapering of dexamethasone

• We are still working on the ideal duration of agents in frontline and how to de-escalate or even discontinue therapy

• IMF Role – we continue to advocate for the PATIENT’S voice in the design of these trials, especially in de-escalation

4. WHAT IS THE OPTIMAL MAINTENANCE STRATEGY

IN MYELOMA?

PERSEUS: Study Design

Maintenance

• Transplanteligible NDMM

• Age 18‒70 years

• ECOG PS ≤2

4 cycles of 28 days

28-day cycles

Continue DR until PD Stop Dara and Restart Dara continue R per criteria

• MRD-negativityc rate was defined as the proportion of patients achieving MRD negativity and ≥CR in the ITT population

– Patients who were not evaluable or had indeterminate results were considered MRD positive

– MRD was evaluated post consolidationd at the time of suspected CR/sCR; at 12, 18, 24, 30, and 36 months after cycle 1 day 1; and yearly thereaftere

aStratified by ISS stage and cytogenetic risk. bDara 1800 mg co-formulated with rHuPH20 (2000 U/mL; ENHANZE ® drug delivery technology, Halozyme, Inc., San Diego, CA, USA); VRd administered as in the VRd group. cMRD was assessed using the clonoSEQ assay (v.2.0; Adaptive Biotechnologies, Seattle, WA, USA) in patients with ≥VGPR post consolidation and at the time of suspected ≥CR. dIn patients with ≥VGPR. eIn patients who achieved CR/sCR and remained on study.

CR, complete response; Dara, daratumumab; DR, daratumumab and lenalidomide; DVRd, daratumumab, bortezomib, lenalidomide, and dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; ISS, International Staging System; ITT, intent-to-treat; MRD, minimal residual disease; NDMM, newly diagnosed multiple myeloma; PD, progressive disease; rHuPH20, recombinant human hyaluronidase PH20; R, lenalidomide; sCR, stringent

PERSEUS: Sustained

MRD-Negativity (10‒5) ≥CR Rates

by P Moreau at the American Society of Clinical Oncology (ASCO) Annual Meeting; May 30–June 3, 2025; Chicago, IL, USA & Virtual

Dr. Joe’s Take on Maintenance

• Historically we know that lenalidomide maintenance prolongs PFS and even improves survival

• Other approaches have added agents to lenalidomide to improve outcomes, especially in higher risk patients

• Due to its convenience and emerging data, there has been a trend to use daratumumab in maintenance

• The recent results from the PERSEUS is quite convincing for its use for up to 2 years

• Several ongoing studies are evaluating the potential to STOP maintenance primarily based on MRD status

• IMF Role – we continue to study MRD and its importance in decision making in MM

5. CAN MRD STATUS GUIDE THERAPY?

The Evolution of Response Assessment in Myeloma

Courtesy of Rafael Fonseca

Dr. Joe’s Take on MRD

• MRD is an incredibly powerful biomarker

• MRD is diagnostic and prognostic currently and will be more ”therapeutic” very soon

• It may help reduce the need of certain more intense therapies like stem cell transplant

• It is a particularly important goal in high risk myeloma

• It is now an accepted endpoint in clinical trials

• I believe it will become standard practice in myeloma to guide escalation and de-escalation of therapy....

• IMF Role – we continue to study MRD and its importance in decision making in MM

6. HOW DO WE OVERCOME HIGH RISK MM?

GMMG-CONCEPT Trial design

Stem cell mobilization after cycle 3

Isa: 10 mg/kg D1,8,15,22 in C1; D1,15 in C2+; K: 20 mg/m² D1,2 of C1; 36 mg/m² D8,9,15,16 of C1 and D1,2,8,9,15,16 in C2+; from 2021 onwards: 56 mg/m² on D1,8,15 and 70 mg/m² on D1,15 in maintenance; R: 25 mg D1-21 all Cycles; d: 40 mg D1,8,15,22 all Cycles (20 mg age >75).

Arm A: app. 15-18 months after inclusion

Arm B: app. 12 months after inclusion

HRMM criteria: ISS stage II or III PLUS ≥1 of: del(17p), t(4;14), t(14;16) and/or ≥3 copies 1q21 (amp1q21)

Primary objective: MRD negativity after consolidation (NGF, 10-5)

Secondary objective: PFS; Selected tertiary objectives: ORR, OS

ASCT, autologous stem-cell transplant; d, dexamethasone; HDT, high-dose therapy; HRMM, high-risk multiple myeloma; Isa, isatuximab; ISS, International Staging System; K, carfilzomib; MRD, minimal residual disease; ND, newly-diagnosed; NGF, next-generation flow; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; R, lenalidomide; TE, transplant-eligible; TNE, transplant-ineligible. Following a protocol amendment in 2021, carfilzomib application was switched to once weekly 56 mg/m2.

Progression-free and Overall Survival

• Median follow-up of 43 months (0-90.2 months)

 1st cohort: 69 months (0-90.2 months)

 2nd cohort: 33 months (5.5-43.3 months)

5Y-OS-rate: 72% (65.0-78.9%)

6Y-OS-rate: 69% (61.2-76.8%)

Lisa B. Leypoldt, MD

Results

Sustaining MRD-negativity was associated with increased PFS

CI, confidence interval; HR: hazard ratio; MRD, minimal residual disease. Clinical data cut-off: April 28, 2025.

Multivariable time-dependent Coxregression analysis showed a prognostic PFS benefit for remaining in MRD negativity versus non–MRD negativity with a hazard ratio of 0.15 (95% CI, 0.07-0.29, p<0.0001)

Results for TE patients. Figure shows a Simon-Makuch plot illustrating the estimated survival while staying in the state of MRD-negativity compared to the estimated survival while staying in the state of MRD-positivity. Patients may switch between the two states under therapy.

PRESENTED BY:

Lisa B. Leypoldt, MD

IMS/IMWG consensus on high risk myeloma definition

Del17p in more than 20% of sorted plasma cells

2 among t(4;14) or t(14;16) or t(14;20)

Dr. Joe’s Take on High Risk Myeloma

• A NEW definition is was JUST released to truly identify those patients at highest risk

• It is genuinely an unmet need in MM, as sadly some still succumb to their disease in the first year of diagnosis

• Patients require combination therapies, given continuously and with MRD negativity as the goal

• It is possible that CAR T Cell therapy may change this approach as even high risk patients can have deep and durable responses to CAR T

• IMF Role – in conjunction with the IMS (International Myeloma Society) we convened the IMWG to write the new definition of high risk MM

7. CAN WE MORE EFFECTIVELY, SAFELY AND CONVENIENTLY GIVE BISPECIFIC ANTIBODIES?

Cytokine Release Syndrome (CRS)

Severity for BsAbs and CAR T Ranges From Mild to Life-Threatening

CAR T: Need to Manufacture

Monitoring for CRS, Neurotoxicity

• Vital signs (eg, temperature, O2 saturation)

• Review of systems and physical exam

– Focus on cardiovascular, pulmonary, and neurologic systems

• Rule out infection

• Laboratory monitoring

– CRP

– Cytokines

– Ferritin

– LDH

• Mental status scoring

RESPIRATORY

Hypoxia

Dyspnea

Capillary leak syndrome

HEPATIC

Transaminitis

↑ ALP

Hyperbilirubinemia

RENAL

↑ Serum creatinine

Renal insufficiency

TLS

HEMATOLOGIC

Anemia

Thrombocytopenia

Neutropenia

CONSTITUTIONAL

Fever

Fatigue, malaise

Headache

NEUROLOGIC

Delirium

Somnolence

Dysphagia

CARDIOVASCULAR

Sinus tachycardia

Hypotension

Arrhythmias

GASTROINTESTINAL

Nausea

Vomiting

Diarrhea

MUSCULOSKELETAL

↑ CPK

Myalgia

Weakness

Neurotoxicity in Immunotherapy

Monitoring for Immune Effector CellAssociated Neurotoxicity Syndrome (ICANS)1,2

 ICE screening tool

 Review of systems and physical examination

– Focus on neurologic systems

 Rule out infection

 If ICANS suspected – Neuroimaging (ideally MRI)

– Diagnostic lumbar puncture for opening pressure and infection tests

 Corticosteroids are typically indicated for ICANS ≥ grade 2

 Patient and care partner information

Abbreviations: AE, adverse event; ICE, immune effector cell encephalopathy. 1. Brudno JN, Kochenderfer JN. Blood. 2016;127:3321-3330. 2. Lee DW, et al. Biol Blood Marrow Transplant. 2019;25:625-638.

ICE Screening Tool for Neurologic Assessment

Dr. Joe’s Take on Managing Immunotherapies

• Every treatment in myeloma goes through an evolution after approval to increase efficacy and reduce toxicity

• We are in the midst of that evolution now

• working towards outpatient management

• understanding side effects

• developing strategies to prevent and treat them rapidly

• sharing information between experts to speed up the process

• The IMF Immune Therapy Registry was designed to do this!

• IMWG guidelines for bispecific antibodies and CAR T Cell therapy

• now with a “living” component by keeping them up to date online

• IMF Role – we are hosting the living guideline with help from our NLB (Nurse Leadership Board)

8. IS THERE AN IDEAL SEQUENCING APPROACH IN

RELAPSED MYELOMA?

Don’t Save the Best for Last!

In every new LOT, ~15-35% of patients are lost

Figure adapted from: Yong, K et al. Br J Haematol 2016;175(2):252-264

Shared Decision-Making Strategies

 Patients and providers should make individualized decisions together regarding treatment

 SHARE approach

 Seek patient participation

 Help the patient explore and compare treatment options

 Assess patient’s values and preferences

 Reach a decision with the patient

 Evaluate the patient’s decision

Noonan K, et al. J Adv Pract Oncol. 2022;13:15-21; Faiman B, et al. Clin J Oncol Nurs. 2019;23:540-42;

International Myeloma Foundation. https://www.myeloma.org/resource-library/tip-card-myeloma-treatment-discussion-tool.

Dr. Joe’s Take on Sequencing

• There really is no IDEAL sequence that we know of in myeloma

Key Principles include:

• Use the most effective therapies as early as possible in the disease course

• in eligible patients sequence CAR T prior to other immunotherapies

• The BCMA target can be used more than once

• Shared decision making (SDM) is critical to matching the right therapy to the patient

• IMF Role – The IMF’s NLB essentially defined SDM and we continue to support the importance of patient preference

9. HOW CAN WE ADDRESS THE GLOBAL

DISPARITIES IN MYELOMA?

Reference:

Liu, X., Zhuang, H., Li, F. et al. Trends and projections of the global and regional burden of multiple myeloma in adults aged 40 and over, 1990–2044. Sci Rep 15, 13595 (2025). https://doi.org/10.1038/s41598-025-96981-w

M-Power = Myeloma Power

Thefactsaresobering:

• MyelomaistwiceascommoninAfrican Americans

• Survival in African Americans in HALFthat of White Americans

• Thedisparityismultifactorial

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

Enhance access to optimal care by educating myeloma providers about the disparity and how to reduce it

Engage the community to increase awareness and provide support

Shorten the time to diagnosis by educating primary care providers to recognize the disease and order the right tests

Juneteenth 2025 - Brooklyn

Dr. Joe’s Take on Disparities

• There is no greater problem in myeloma worldwide!

• It is a combination of multiple factors

• Social determinant of Health

• Delayed Diagnosis

• Reduced Access to Novel therapies

• It is not an easily solved problem but critical advances can be made

• The IMF M-Power program is an example of a strategy that can be applied more broadly with short and long term goals

• IMF Role – we are truly a leader in reducing health disparities in medicine through M-Power and GMAN (Global Myeloma Action Network)

10. ARE WE CURING MYELOMA?

Survival in multiple myeloma has improved over time

Overall survival by decade of MM diagnosis1

CI, confidence interval; HR, hazard ratio; MM, multiple myeloma; OS, overall survival.

Long-Term (≥5 Year) Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1

Patients With Relapsed/Refractory Multiple Myeloma

Peter M Voorhees1, Thomas G Martin2, Yi Lin3, Adam D Cohen4, Noopur Raje5, Myo Htut6, Abhinav Deol7, Mounzer Agha8, Jesus G Berdeja9, Binod Dhakal10, Andrzej J Jakubowiak11, Samir Parekh12, Hui Li13, Rocio Montes de Oca14, Huabin Sun15, Nikoletta Lendvai15, Deepu Madduri15, Mythili Koneru16, Nitin Patel16, Sundar Jagannath12

1Atrium Health/Levine Cancer Institute, Wake Forest University School of Medicine, Charlotte, NC, USA; 2University of California, San Francisco, CA, USA; 3Mayo Clinic, Rochester, MN, USA; 4Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 5Massachusetts General Hospital Cancer Center, Boston, MA, USA; 6City of Hope Comprehensive Cancer Center, Duarte, CA, USA; 7Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA; 8UPMC Hillman Cancer Center, Pittsburgh, PA, USA; 9Tennessee Oncology, Nashville, TN, USA; 10Medical College of Wisconsin, Milwaukee, WI, USA; 11University of Chicago, Chicago, IL, USA; 12Icahn School of Medicine at Mount Sinai, New York, NY, USA; 13Johnson & Johnson, Shanghai, China; 14Johnson & Johnson, Spring House, PA, USA; 15Johnson & Johnson, Raritan, NJ, USA; 16Legend Biotech USA Inc., Somerset, NJ, USA

https://www.congresshub.com/Oncology/ AM2025/Cilta-cel/Voorhees

Copies of this presentation obtained through Quick Response (QR) Codes are for personal use only and may not be reproduced without permission from ASCO® or the author of this presentation.

Presented by PM Voorhees at the American Society of Clinical Oncology (ASCO) Annual Meeting; May 30–June 3, 2025; Chicago, IL, USA & Virtual

CARTITUDE-1 Long-Term Remission:

One-Third of Patients Were Progression-Free for ≥5 Years

Overall population (N=97); median follow-up: 61.3 months

Progression-free survival

32 of 97 (33%) patients were treatment- and progression-free at ≥5 years

Dr. Joe’s Take on Cure

• I like to define cure in the way someone on the street would likely define it... someone is given limited therapy then no longer has to think about the disease

• We have always had a very small fraction of patients who with limited therapy have particularly long remissions

• I believe that fraction continues to grow with the novel approaches we are providing

• It will not happen overnight – but will be the result of a global coalition against myeloma bringing together the best science, clinical trials, experts and motivated patients...

• IMF Role – we are leading the effort to “define” cure for scientific purposes and conduct “cure” trials...

Bonus Topic – Down with Dex!

Dr. Joe’s Approach to Dex

• Dexamethasone Dose De-escalation Protocol

1. Assess 40 mg versus 20 mg weekly starting dose

2. Limit starting dose to 2 to 3 months

3. Then taper dose each month over the course of 3 to 4 months

4. Plan to stop dexamethasone at 6 months

5. Regular assessments for toxicity and de-escalate sooner if clinically indicated Join the DOWN with

FFinal Thoughts...

• There are still MANY more unanswered questions! • But the future for myeloma patients is genuinely bright • We must

all be a part of the solution!

Turning Personal Stories into Powerful Advocacy:

How to Get Involved and Make a Difference

Michael Riotto

IMF Grassroots Advocacy Consultant, Support Group Leader (Philadelphia,

PA)

Turning Personal Stories into Powerful Advocacy: Our Advocate Panel

1. Ensure Access to Care: We advocate to ensure all myeloma patients have equitable, comprehensive, patient-centered care without insurance barriers that limit options or delay treatment initiation.

2. Eliminate Financial Barriers: We advocate for policies that allow myeloma patients access to treatments and supportive care interventions without facing financial hardships.

3. Advance Myeloma Research: We advocate for annual appropriations funding for myeloma research and the advancement of clinical trial eligibility and research protocols that ensure representation from diverse populations.

The IMF Grassroots Advocacy Program is multi-faceted and growing

• Advocacy Training & Leadership Development

• Policy and Legislative Education

• Grassroots Campaign Planning

• Health Policy Forums & Roundtables

• Advocacy Resource Development

• Storytelling and Personal Narratives

Stretch & Morning Break

Serdar Erdogan Myeloma has no Borders

IMF Director of GMAN

EU/ME Patient Programs

Global Myeloma Action Network (GMAN) | Uniting a Global Patient Community

GMAN is a global consortium of 50 myeloma patient organizations representing 46 countries.

GMAN works at the intersection of research, advocacy and member support in collaboration with patients, care partners, physicians/KOLs, policymakers, the pharmaceutical industry and other global stakeholders.

Research

Increase awareness of and participation in clinical trials worldwide.

Access

Influence policymaking for improved access to timely diagnosis and critical therapies.

Member Support

Education, awareness and capacity building to strengthen GMAN’s National Member Organizations.

GMAN’s National Member Organizations | Global Reach

GMAN brings together 50 National Member Organizations from 46 countries across 5 continents

EUROPE & MIDDLE EAST (29)

MYMU BELGIUM

MIJELOM CROATIA

CZECH MYELOMA GROUP

NA - IMF USA

KPMM CZECH REPUBLIC

ARMENIAN HEMATOLOGY ASSOCIATION

MYELOMA UND LYMPHOMHILFE ÖSTERREICH

LATAM - COLOMBIA

FUNLEUCEMIALIMFOMA

CHILE, PARAGUAY & URUGUAY

FUNCA PARAGUAY

AUMM URUGUAY

FUNDACION MYELOMA CHILE

LATAM – BRAZIL

IMF LATIN AMERICA

MULTIPLES MYELOM SELBSTHILFE ÖSTERREICH

DANSK MYELOMATOSE FORENING

SYOPAPOTILAAT FINLAND

AF3M FRANCE

LHRM GERMANY

AMEN ISRAEL

AIL ITALY

AFRICA

KENYAAMPATH

ASIA PACIFIC

ICELANDIC MYELOMA ASSOCIATION

BLODKREFTFORENINGEN NORWAY

CARITA POLAND

POLISH ASSOCIATION FOR MYELOMA PATIENTS

FUNDACJA CENTRUM LECZENIA SZPICZAKA POLAND

APLL PORTUGAL & APCL PORTUGAL

MYELOMA EURONET ROMANIA

MYELOMA MULTIPLEX CSOPORT HUNGARY

ASSOC. OF MYELOMA PATIENTS OF SERBIA

SLOVAK MYELOMA SOCIETY

ASSOC. OF PATIENTS WITH BLOOD DISEASES SLOVENIA

SLOVENSKO ZDRUZENJE BOLNIKOV

CEMMP SPAIN

KOREA BLOOD CANCER ASSOCIATION

ASIA PACIFIC (8)

ASIAN MYELOMA NETWORK (6)

MYELOMA FRIENDS INDIA

MYELOMA AUSTRALIA NA - MYELOMA CANADA

LATAM - ARGENTINA

FUNDACIÓN ARGENTINA DE MIELOMA

BLODCANCERFORBUNDET SWEDEN

STIFTUNG ZUR FÖRDERUNG DER

KNOCHENMARKTRANSPLANTATION SWISS

MYELOMLA YASAM TURKEY

ASSOCIATION FOR PATIENTS WITH CHRONIC LYMPHOPROLIFERATIVE DISEASES - UKRAINE

KANSER SAVASCILARI DERNEĞI TURKEY

MYELOMA UK

AUSTRALIA

NEW ZEALAND

MYELOMA NEW ZEALAND

GMAN: One voice globally, collaboration regionally, and independent at national level GMAN’s National Member Organizations | Global Reach

Umbrella Organizations

Finland. Kenya, Paraguay, Turkey

Myeloma Groups

Hungary, Philippines, Thailand

Blood Cancer Organizations

Armenia, Colombia, Italy, Norway, Portugal(2), South Korea, Sweden, Ukraine

Well Structured Organizations

Australia, Brazil, Canada, Denmark, France, Italy, United Kingdom. United States

GMAN’s National Member Organizations

Denmark, France & Italy: Strong regional structure, volunteers operate the organization

Czechia: Strong clinical trial integration with support groups

Germany: Focused regional support groups

Hong Kong, Malaysia, Philippines, Singapore, Thailand, Taiwan, South Korea:

Patient organizations are growing under the roof of AMN

Argentina, Brazil, Chile, Colombia, Uruguay:

Patient organizations are growing under the roof of LAMN

GMAN Annual Summit | 2025

Topics Included:

• Barriers to accessing both standard of care & novel therapies

• HTA and regulations in EU

• Capacity building

June 2025 | Milan, Italy

• 2 days

• 30 country patient leaders attending

• 4 national educational grants awarded

• Scientific updates, panel discussions, policy and awareness

GMAN Annual Summit | 2025

Mercy Oduor receiving grant on behalf of AMPATH:

Expanding Early Detection, Access and Support for Myeloma Patients in Kenya

Susie Novis Durie

Grants:

2025 | Grant Recipients

• Armenia

• Kenya

• Poland

• Serbia

Each project is awarded with $8,000 USD

Armenian Hematology Association

“Myeloma Armenia 2025/26 – National Educational Seminars on MM”

AMPATH - The Academic Model Providing Access to Healthcare

Expanding Early Detection, Access, and Support for MM Patients in Kenya

CARITA Foundation

“In The Blood” – A Quarterly Magazine for Myeloma Patients & Carers

Association of Myeloma Patients Serbia

Knowledge Unites the CoMMunity

PROJECT FROM CROATIA:

A MEAN DISEASE WITH ORDINARY SYMPTOMS

Case Study: Mijelom CRO

Mijelom CRO: A Mean Disease with Ordinary Symptoms

Objectives:

 Educate and remind general medical practitioners about myeloma and amyloidosis.

 Raise local awareness about multiple myeloma.

 Connect people who are affected by these diseases, living in smaller towns within Zagreb Municipality and provide printed materials.

Mijelom CRO: A Mean Disease with Ordinary Symptoms (Results)

Samobor’s event attracted GPs and nurses

Dugo Selo’s event welcomed mainly patients and families (connection to existing patient).

Participants valued sharing experiences and networking.

Future efforts should focus more on GPs and physiotherapists to enhance impact.

Printed materials provided free to participants and distributed amongst 13 hospitals in Croatia

Raising awareness especially among GPs, nurses, and physiotherapists

Patient handbook - Physical Activity and Sport for People with Myeloma

PROJECT FROM DENMARK: LIVING WITH MYELOMA

Danish Project: Identifying Challenges in Living With Myeloma

Dansk Myelomatose Forening

• Celebrating 25 years of support for myeloma patients.

• Currently has 1,200 members in Denmark.

• Represents approximately 34% of myeloma patients in the country.

• Focus on raising awareness and providing resources.

• Aims to improve the quality of life for patients and families.

Danish Project: Identifying Challenges in Living With Myeloma

 Both patients and relatives shared experiences and insights on the theme of cognitive challenges.

Responses highlighted difficulties in coping with everyday

Cognitive challenges were a prominent concern for care partners

Terms like “chemo brain” and “mental fog” were frequently mentioned.

Danish Project: Identifying Challenges in Living With Myeloma

SMART Training, a Danish-developed program that combines cognitive and motor exercises was implemented.

25.5% indicated experiencing at least one area of severe impairment, and 65.6% reported challenges rated 3 or higher on a 0–5 scale.

International Bill of Rights

2026 MAM + GMAN Campaign Idea

Each country can work on having a key point of interest in their territory light up in red supporting MAM for the month of March. It would be great if….Paris, Rio, Niagara Falls, Toronto, San Francisco, New York could have a landmark lit in red!!!

Any Questions?

Fireside Chat #1:

Screening, Smoldering Myeloma & Frontline Therapy

Joseph Mikhael, MD

Shaji Kumar, MD Mayo Clinic, Rochester, MN

IMF SAB & IMWG

Robin Tuohy Morning Wrap-Up

Share a Memory

Headshots available by Jason London from 12

- 1 PM

Reminder to wear your name badge that includes your dinner tickets throughout the program

Lunchtime 12:00 - 1:00 PM

Welcome Back!

Fireside Chat #2:

Maintenance & Relapsed Therapy

Joseph Mikhael, MD

Kumar, MD

Support Group Leader Guide:

Making Sense of Lab & Diagnostic Tests in Multiple Myeloma

Beth Faiman, PhD, MSN,

APN-BC, AOCN, BMTCN, FAAN,

FAPO

Cleveland Clinic Taussig Cancer Institute

IMF Nurse Leadership Board

Overview

• Describe common tests in myeloma and how to interpret

• Review the concepts of biomarkers and genomics

• Identify important findings of pathology and radiology reports

Biomarkers and Genomics are Important in Myeloma

Biomarker: A distinctive biological characteristic that can be objectively measured to diagnose disease, determine response to medications, or estimate prognosis

Numerous biomarkers in Myeloma

Genomics: A discipline concerned with mapping the genes (“gen-”) and chromosomes (“-ome”) of an organism as well as the identification of dysregulated or misprogrammed genes

Genomics as a science has gained popularity with the human genome project (HGP), an international, collaborative research program completed in 2003 which “mapped” the human genome and developed a “blueprint” of human genetic material

The HGP revealed there are approximately 20,500 human genes in which 99% of humans share

Changes in genes arise from a series of mutations, alterations to normal cells

What is Multiple Myeloma (MM)?

Cancer of the bone marrow

plasma cells that make excess proteins in the blood, urine

Understanding Your Test Results, International Myeloma Foundation 2025.

Not everyone with an abnormal protein has multiple myeloma -

Biomarkersandgeneticscan helpdiagnose

Spike on SPEP/UPEP

Abnormal Freelite Test

Bone Marrow < 10% PCs

Low Risk Risk of Progression: ≈ 1% per year

High Risk: Likely to Progress to Active MM Within 2 Years MGRS*

M-spike ≥ 2 g/dL

Freelite Ratio ≥ 20%

Bone Marrow ≥ 20%

CRAB Criteria

Calcium Elevation

Renal Dysfunction

Anemia

Bone Lesions

MDEs

Bone Marrow ≥ 60% PC

Freelite Ratio ≥ 100

CCR < 40 mL/min

MRI ≥ 1 focal lesion ≥5mm

CCR = creatinine clearance rate; MDE = myeloma-defining event; MGUS = monoclonal gammopathy of undetermined significance; MM = multiple myeloma; MRI = magnetic resonance imaging; PC = plasma clone; SMM = smoldering multiple myeloma; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis. aMonoclonal gammopathy of renal significance (MGRS) does not meet criteria for myeloma but has kidney manifestation; kidney biopsy is the gold standard for diagnosis. Rajkumar SV, et al. Lancet Oncol. 2014;15(12):e538-48. Bridoux F, et al. Kidney Int. 2015;87(4):698-711. Terpos E, et al. Lancet Oncol. 2021;22(3):e119-e130. Hillengass J, et al. Lancet Oncol. 2019;20(6):e302-e312.

What kind of tests can one expect?

There are several tests you can expect:

Blood

Urine

Bone Imaging

Bone Marrow Biopsy

Ask your provider how often these need to be done (Monthly, every 1, 3, 6 months or annually)

Know who is responsible for ordering and monitoring these tests (community or academic center)

Interpreting the Blood Tests: “Monoclonal Protein” Work Up

Organ function: complete blood count, blood chemistry panel

Serum protein electrophoresis – “MSPIKE”

How much monoclonal is present? Low(0.1gms) or high (10.00gms)?

Serum immunofixation – “IgG Kappa, or IgA lambda”, etc…..

What type of monoclonal

Serum free light chains “Kappa or Lambda”

Does one have a high serum free Kappa or Lambda?

Serum immunoglobulins – total values

IgG, IgA, IgM

Urine studies, protein electrophoresis and immunofixation, light chains 24-hr is the best, especially if there is proteinuria on recent UA

In a recent study, the age of first chromosomal gain to age of sample collection 30-40 yrs

MGUS to MM

Gene translocations can be present many yrs before genetic changes

Alberge, J.-B., Dutta, A. K., Poletti, A., Coorens, T. H. H., Lightbody, E. D., Toenges, R., Loinaz, X., Wallin, S., Dunford, A., Priebe, O., Dagan, J., Boehner, C. J., Horowitz, E., Su, N. K., Barr, H., Hevenor, L., Towle, K., Beesam, R., Beckwith, J. B., . . . Ghobrial, I. M. (2025). Genomic landscape of multiple myeloma and its precursor conditions. Nature Genetics, 57(6), 1493-1503. https://doi.org/10.1038/s41588-025-02196-0

Testing Needed To Define The Diagnosis

Lab tests – Blood and Urine

– CBC + differential, complete metabolic panel (albumin, creatinine, calcium), Beta-2 Microglobulin

– Serum protein electrophoresis (SPEP), Free light chain assay with kappa/lambda ratio, serum immunofixation

– Urine immunofixation & protein electrophoresis (UPEP)

Bone marrow biopsy & aspirate

– Plasma cell concentration (%)

– Congo Red staining if concern for AL-Amyloid

– Cytogenetics, “BRAINS” of the cells with “FISH”, for genetic information on prognosis

Imaging:

– Skeletal survey

– WB-LD CT ± PET (Whole body low dose CT)

– MRI ± PET scan

When

do you Treat Patients for Multiple Myeloma

The current goal is to find patients at

Clonalbonemarrow≥10%,orplasmacytomaANDany one or more Myeloma Defining Events(MDE)

Common findings in Myeloma: Anemia

• A reflection of the bone marrow’s ability to produce cells that are obtained through peripheral blood draws

 Lab values vary slightly amongst institutions and laboratories

• Anemia is a functional inability of the blood to supply the tissue with adequate oxygen for proper metabolic function

• It is not a disease, but rather the expression of an underlying disorder or disease

• Morphologic approach: MCV

CBC (Complete Blood Count): A window into your body’s ability to make healthy

red cells, white cells and platelets

WhiteCells fight infection

Hemoglobincarries Oxygen Platelets Clot your blood

• The “differential” –numbers at the bottomare a break down of the healthy cells

Tip: Make sure to look at the reference range, AND look for your past results (high,)low? Stable?

This shows findings of anemia and low blood platelets.

Complete Metabolic Panel (Blood test)

Indicators of myeloma-related organ dysfunction on CMP

• BUN

• Creatinine

• Calcium

• ALB

• Alkaline phosphatase

Metabolic Panel: Shows organ function (kidney,liver,bone)

Glucose: Diabetes?

ALT, AST, (liver) ALK

PHOS: Bone or liver

Total Protein, Albumin: low in AL amyloidosis, Active myeloma due to high total Protein levels

Many of these are important Electrolytes to keep our bodies in balance

Creatinine/ BUN: Kidney function

LD (LDH): tumor burden, prognosis

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)

Prevention

– Drink, Drink, Drink

– Avoid certain medications, when possible

Treatment

– Treatment for myeloma – Hydration – Dialysis

Myeloma Cells Can Cause Damage To Bones

Most

myeloma patients will experience

bone involvement at some point; it is important to protect your bone health

► Approximately 85% of myeloma patients develop bone disease

► Protecting bone health

– Nutrition

– Weight-bearing activity

– Medications

• Vitamin D

• Calcium (if approved by doctor)

• Bone strengthening agents: Zometa® (zoledronic acid), Aredia (pamidronate), or Xgeva® (denousamab)

► Report new pain to your health care provider

SPEP and UPEP – looks at “M-SPIKE”

Monoclonal Proteins and Immunoglobulins

Immunoglobulin structure

Monoclonal Proteins and Immunoglobulins

Hypogammaglobulinemia:

Serum (Blood) Free Light Chains

Normal Abnormal

 Kappa light chain: 3.3–19.4 mg/L

– Normal ratio for free lightchain kappa: Lambda is 0.26–1.65

 Elevation of kappa: Lambda ratio suggests kappa light chain M gammopathy is present

Increasing trend of kappa sFLC in a patient with MGUS that transforms to myeloma

 Lambda light chain: 5.7–26.3 mg/L

– Kappa: Lambda free lightchain ratio < 0.26 typically defined as having M lambda free light chain

 Decreased in Kappa: Lambda ratio suggests lambda light chain M gammopathy is present/dominant clone

(H)

(H)

(H)

(H)

24-Hour Urine for Protein and Immunofixation

Why is my provider asking for a 24-hr urine evaluation if a secondary analysis says it doesn’t change response?

- Still very accurate to detect a monoclonal protein for diagnosis of MM, amyloidosis

- Measures kidney health, bone loss

- Study procedures will still require for some time

Lab values vary slightly amongst institutions and laboratories

Bone Imaging Tests

Whole Body Low -Dose CT (WBLDCT)

Best for early screening for bone disease

Response assessment: active residual disease

MRI

WB or spine + pelvis

Gold standard to assess bone

marrow involvement

CT = computed tomography

DEXA = dual-energy x-ray absorptiometry

MRI = magnetic resonance imaging; PET = positron emission tomography

WB = whole body

WBLDCT = whole-body lowdose computed tomography

NOTE: Bone scan (DEXA) for bone density is useful in some situations

Brigle K, et al. JAdv PractOncol . 2022;13(Suppl 4):7-14. Hillengass J, et al. LancetOncol . 2019;20(6):e302-e312. Rome SI, et al. ClinJ OncolNurs . 2017;21(5 suppl):47-59. Faiman B. ClinLymphomaMyelomaLeuk . 2014;14:436-440. Dimopoulous M, et al. Leukemia. 2009;23(9):1545-1556.

PET Scan Example

What is DNA?

• Integral to the identification of the human genome was an understanding of the coiled double helix structure known as deoxyribonucleic acid (DNA), covered with proteins called histones

• Genetic information is contained in cells, which forms a sequence

• A DNA consists of four nucleotide base pairs including: adenine (A), thymine (T), guanine (G) and cytosine (C)

• Each base pair develops a sequence which can be followed and replicated

• For example, the purine adenine always pairs with the pyrimidine thymine (“A with T”), while the pyrimidine cytosine always pairs with the purine guanine (“C with G”)

• All individuals are born with DNA that express genes and represents opportunities for variability from one human to the next

Detection of Genetic Alterations in Myeloma

• Cytogenetics

• Large fragments of DNA, easily visible with a microscope

• FISH (Fluorescence In Situ Hybridization)

• Much smaller fragments of DNA (closer to the size of individual genes/gene regions) – requires tagging with a fluorescent substance, visible under a special fluorescent microscope

• Molecular / Next Generation Sequencing (NGS)

• Submicroscopic alterations in the nucleotides (single or clusters of few nucleotides) that make up the sequence specific for each gene

Bone Marrow Aspirate and Biopsy: A way to obtain DNA

Adult red marrow has a large reserve capacity for cell production

Only found in the upper ends of the femur and humerus; flat bones of the sternum, ribs, cranium, pelvis, and vertebrae

Important to characterize plasma cell percentage, FISH, and cytogenetics

Bone Marrow Biopsy with a Needle

In humans, each cell normally contains 23 pairs of chromosomes –total of 46. Twenty-two of these pairs, called autosomes, look the same in both males and females.

The 23rd pair, the sex chromosomes, differ between males and females.

Chromosomal Analysis

Trisomies can be seen in chromosomes 1, 5, 9, 11, 15, 19, a tetrasomy can be seen in chromosome 7 and deletions of chromosome can be seen in chromosomes 14, 16, 17 and 21.

Process for Cytogenetics (Karyotyping)

Require presence of live cells or intact nuclei Can be analyzed on bone marrow, peripheral blood, body fluids, and solid tissue

Cells exposed to mitotic inhibitors, hypotonic solution, and fixation followed by banding methods

Can identify related and distinct clonal populations Allows for stratification into favorable, intermediate, and adverse-risk

Fluorescent In-Situ Hybridization (FISH)

More sensitive to detect specific translocations

Performed on same sample submitted for chromosome analysis

Blood, bone marrow, body fluids

Detection of gene amplification

Confirmation of rearrangements detected on conventional cytogenetics

Detection of early relapse based on lineage of neoplastic cells

FISH image showing an abnormal cell with one red signal and two green signals, indicating the long arm of one copy of chromosome 7 is deleted

Recap: Detection of Genetic Alterations in Myeloma

Cytogenetics

Can detect (Screening):

- Any translocations

- deletions

- additional material (large fragments)

FISH

Can detect (specific to the genes interrogated):

- Translocations

- Deletions

- Additional copies of genes (amplification)

Nucleotides

Can detect:

- DNA

- Sequencing – mutations (single bases)

- PCR: Gene rearrangements

- RNA (RT-PCR)

- Specific translocations

What does Risk With Multiple Myeloma Mean?

Prognosis Findings from Bone Marrow Biopsy

Itisimportanttoknowthenumberofbonemarrowplasmacellsandprognosisinformation

No abnormalities detected

OR

Abnormalities that are not defined as high-risk

• Trisomies

• t (11;14)

• t (6;14)

Identified by FISH

• t (4;14)a

• t (14;16)

• t (14;20)

• Del (17p)

• gain (1q)a

Double hit: any 2 high-risk factors

Triple hit: any 3 high-risk factors

CKS1B = cyclin-dependent kinases regulatory subunit 1 gene; FISH = fluorescence in situ hybridization; TP53 = tumor protein 53. aHigh risk if detected in SMM; intermediate risk in MM according to Rajkumar SV 2022. Rajkumar SV. AmJofHematology.2022;97(8):1086-1107.

New categories for high risk: What does this mean?

Consider 17P high risk even if not ISS 3

Do you have to check TP53 status if 17P is present? Yes

– since sometimes 17 p without TP53 mutational status present

TP53: Biallelic TP53 alterations can involve a mutation on one allele and a deletion on the other, or two distinct mutations on each allele

Bialleic del (1p32), 10% of NDMM; in 20% of these cases, if bialleic then poor prognosis

Example: Biallelic deletion of 1p32:This means both copies of the chromosome region 1p32 are deleted, resulting in a loss of both allele

t(4;14) high risk if assess w/ another intermediate lesion

Prognosis: Minimal Residual Disease (MRD)-Negative

ASCT = autologous stem cell transplant; CR = complete response; FDA = US Food and Drug Administration; MRD = minimal residual disease; VGPR = very good partial response. Munshi N, et al. Blood Adv. 2020;4(23):5988-5999. ClonoSEQ website. Accessed March 15, 20222. https://www.clonoseq.com/. ClonoSEQ® [technical summary]. Seattle, WA. Adaptive Biotechnologies; 2020. Accessed March 23, 2023. https://www.clonoseq.com/technical-summary/.

• Predict outcomes

• Support treatment decisions?

• VGPR or better

• Often prior to transplant or cellular therapy

• Often retest at set intervals (eg, every 6-months)

• ClonoSEQ—FDA cleared for diagnostic use

• Within a clinical trial protocol

• Nice to know vs. need-to-know information

Bone marrow biopsy report

Complex Cytogenetics, FISH

IgG, IgA , IgM, κ, λ Spectra

Mass Spectrometry

Peak Analyzer Isotyper Interpreter Analyzer System

Current Detected M -Proteins M -Protein, FLC and Ig Quant History

3D Spectra History

2D Spectra with Peaks highlighted

Lab Tech and Lab Director Review Manual regating if necessary Release

Timeline of mass-fix

Initial development of MALDI-TOF method

EXAMPLE OF DYNAMIC RANGE IN AN IGG LAMBDA MM

PATIENT

80 g/L Max Mode 0.01 g/L 80 g/L

M-protein slowly decreasing

1+ year course of MM treatment

IMPLICATIONS OF LOWER LOQ FOR M-PROTEIN QUANTITATION

SPEP and IFE

• 65% of M-protein positive samples were below the LOQ of SPEP

• The range of IFE positive samples below the SPEP LOQ was 0.05 g/L to 40 g/dL by Mass-Fix

Mass-Fix

• 0.03% of M-protein samples had values below LOQ of Mass-Fix

Mass

Special Considerations With Antibody Therapy

Interference with IFE laboratory tests

Daratumumab, isatuximab, and elotuzumab are IgG antibodies that co-migrate with IgG M-protein

IFE cannot distinguish between therapeutic IgG antibodies and IgG Mprotein; Lowers apparent CR rates

Mass spectrometry (available in some centers) can resolve antibody interference

• Patients with MM can be by MS replacing SPEP and IFE

• MS also has a role in amyloidosis (eg, it has improved accuracy for typing amyloid plaques and has led to the discovery of new types of amyloid)

CR = complete response; IFE = immunofixation electrophoresis; IgG = immunoglobulin G; M-protein = monoclonal protein; SPEP = serum protein electrophoresis.

Mills JR, Murray DL. J Appl Lab Med. 2017;1(4):421-431. Murray DL, Dasari S. Clin Lab Med. 2021;41(2):203-219. Deulofeu M, et al. ACS Chem Neurosci. 2023;14(2):300-311. Moore LM, et al. Clin Chim Acta. 2019;492:91-94.

How Well Treatment Is Working: IMWG Myeloma Response

and Relapse Criteria Assessment

CR Complete

Remission

CR: myeloma protein undetectable in serum or urine (negative immunofixation); no more than 5% plasma cells in bone marrow; no new lytic lesions; plasmacytomas resolved

VGPR Very Good

Partial

Remission 90% reduction in myeloma protein

PR

Partial

Remission At least 50% reduction in myeloma protein

PD Progressive Disease Increase of > 25% from lowest response value in myeloma protein or other assessment

Further categorization of CR: sCR, MRD-negative

Know:  Order labs regularly

 Know who is monitoring (local or referral center)

 Monitor for relapse

– CRAB symptoms OR increase of 25% in M protein from the lowest point

How Patients With Myeloma Relapse

Myeloma protein

No symptoms, “Biochemical” Relapse

• Sequentially rising myeloma protein or free light chain (>25% increase from low point)

• No other symptoms

• Decisions: if, when, how to treat

New symptoms, “Symptomatic”

 New, worsening bone pain

 Increasing fatigue, anemia

 Next step: relapse workup; many therapy choices

Knowing Your Myeloma Numbers

Immunoglobulin: (Ig)___: _______

FLC: kappa _____ lambda _____

G A M E D

Ratio (K/L) ______ M-spike _______ Bone Marrow Plasma Cells: _____% Urine Protein: _____mg/24hours M-spike _____mg/24hours

What questions should I ask about treatment?

• It is OK to ask your provider about lab results & possible treatments

• Consider trade offs

• Consider burden versus benefit

• If clinical trials are not offered, please ask if one is right for you!

SHARED DECISION-MAKING

Be empowered to be part of the treatment decision-making, come prepared with questions

• Ask for time to consider options (if needed/appropriate)

• Understand options; consider priorities

• Use reliable sources of information

• Use caution considering stories of personal experiences

• Consider your goals/values/preferences

• Express your goals/values/preferences; create a dialog

• My top priority is [goal/value]; additional [preferences] are also important.

• I think [treatment] may be a good choice given my priorities… What do you think?

• Arrive at a treatment decision together

TREATMENT DECISION

Preference

THE MEMBERS OF YOUR TEAM

Understand their different roles Myeloma specialist: for myeloma care

Primary care: for health screening, general check ups, vaccinations

Others: for specific needs (Kidney, Bone)

Keep a contact list of your providers

Come prepared to office visits:

Bring a list of current medications, prescribed and over the counter

Write down your questions and concerns. Prioritize them including financial issues

Have there been any medical or life changes since last visit?

Primary Care

(PCP)

Subspecialists

You and Your Caregiver

Current symptoms - how have they changed (improved, worsened, stable)? Keep a symptom diary. Bring it along

Communicate effectively: your health care team can’t help if they don’t know

Family/Support Network

Allied Health Staff

• Blood, urine, bone and bone marrow testing can provide important information into the state of your myeloma

• Regular monitoring is important for all patients with an abnormal protein

• Don’t be afraid to ask questions about your labs, or treatments

Robin Tuohy Day 1 Wrap-Up

Headshots available by Jason London from

4:30 - 5:30 PM

Leaders who are Health Care Providers, please choose either option to attend

Day 1 Wrap Up

3:30PM – 60-minute session

Please attend the option you selected:

Care Partners (Gale)

Patients (Valhalla)

4:30PM – Open Options

Walk around Viking Lake

Indoor Pool (2nd Floor)

Lawn Games (Valhalla Terrace)

Rest & Relax

Resilience Gallery

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6:00PM – Networking & Evening Reception (Valhalla Terrace & Prefunction North)

7:00PM – Dinner (Valhalla Ballroom)

Tomorrow: 6:30 – 7:45AM – Breakfast (Kyndred Hearth)

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