Best of 2022 ASCO & EHA

Thank you to our sponsors!

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Hybrid ASCO 2022 (in-person/ online) Total ASCO abstracts for 2022 = 5,198 Myeloma Abstracts = 168  Plenary Session = 1  Oral = 13  Poster Discussion = 15  Poster Session = 81  Publication Only = 58

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DETERMINATION Trial

https://www.myeloma.org/videos/updates-phase-3-determination-trial-rvd-asct-r-maintenance-progression-ndmm-patients

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DETERMINATION: study design and patient disposition DETERMINATION: Delayed vs Early Transplant with Revlimid Maintenance and Antimyeloma Triple Therapy RVd cycle 1 (N=729)

Arm A: RVd-alone (N=357)

RVd cycles 2-3

Stem cell collection

Arm B: RVd+ASCT (N=365)

RVd cycles 2-3

Stem cell collection

R maintenance (N=291)

RVd cycles 4-8

Randomization (N=722) Stratified by: ISS disease stage Cytogenetic risk

Each RVd cycle (21 days): R 25 mg/day PO, days 1-14 V 1.3 mg/m2 IV/SC, days 1, 4, 8, 11 Dex 20/10 mg PO, days 1, 2, 4, 5, 8, 9, 11, 12

Melphalan 200 mg/m2 + ASCT (N=310)

Induction ± ASCT + consolidation treatment duration = ~6 months

RVd cycles 4-5

R maintenance (N=289)

Lenalidomide maintenance Months 1-3: 10 mg/day Month 4 onwards: 15 mg/day

Primary endpoint: PFS Secondary endpoints: response rates; DOR; TTP; OS; QoL; safety d/Dex, dexamethasone; DOR, duration of response; ISS, International Staging System; IV, intravenous; PO, orally; R, lenalidomide; SC, subcutaneous; TTP, time to progression; V, bortezomib

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DETERMINATION: Key findings – efficacy Patients alive and free from disease progression after 5 years Highly significant increase in progression-free survival (PFS) with use of ASCT

% 0

10

20

30

40

50

RVd+ASCT •Risk for patients of their disease progressing was 53% higher for those not receiving ASCT

60

55.6

41.5

RVd alone

Patients alive after 5 years No difference in overall survival (OS)

Similar response rates between arms

•But patients remain in response for longer with RVd+ASCT vs RVd-alone: 56.4 months vs 38.9 months •In patients who were tested to date, the proportion with no remaining traces of disease (‘MRD-negative’) was higher: 54.4% vs 39.8% •But those patients achieving MRD do just as well in terms of PFS, regardless of treatment

20

40

60

80

RVd+ASCT

80.7

RVd alone

Response rate, %

•Patients have been followed for a median of 76 months •Only 28% of patients received delayed ASCT to date, with others all treated with next generation novel agents and monoclonal antibodies

% 0

100 90 80 70 60 50 40 30 20 10 0

79.2 RVd+ASCT

RVd-alone 82.7

46.9

97.5

95

79.6

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Complete response or better Very good partial response or better

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Partial response or better

Black Swan – ctDNA Analysis

https://www.myeloma.org/videos/ctdna-analysis-relapse-association-primary-rrmm-patients-receiving-secondary-salvage-therapy

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Bi-specifics and CAR T-cell therapies 9

MajesTEC-1 and TRIMM-2: teclistamab Teclistamab is an investigational, fully humanized IgG4, T-cell redirecting, bispecific antibody targeting both BCMA (B-cell maturation antigen) and CD3, the T-cell receptor.

Overall Response Rate (ORR) = 64%

Deep durable responses https://www.myeloma.org/videos/updated-efficacysafety-results-majestec-1teclistamab-relapsedrefractory-patients

Other abstracts about teclistamab are also available on the ASCO and EHA websites: https://meetings.asco.org/abstracts-presentations and https://library.ehaweb.org/

https://www.myeloma.org/videos/updates-phase-1b-trimm-2-study-resultsteclistamab-plus-daratumumab-rrmm-patients

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Other trials: teclistamab Teclistamab is an investigational, fully humanized IgG4, T-cell redirecting, bispecific antibody targeting both BCMA (B-cell maturation antigen) and CD3, the T-cell receptor.

https://www.myeloma.org/videos/efficacy-teclistimab-versus-currenttreatments-patients-triple-class-exposed-relapsed

Other abstracts about teclistamab are also available on the ASCO and EHA websites: https://meetings.asco.org/abstracts-presentations and https://library.ehaweb.org/

https://www.myeloma.org/videos/evaluation-teclistamab-rrmm-patientsfollowing-exposure-other-bcma-targeted-agents

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Other trials: teclistamab Teclistamab is an investigational, fully humanized IgG4, T-cell redirecting, bispecific antibody targeting both BCMA (B-cell maturation antigen) and CD3, the T-cell receptor.

Matching-adjusted indirect comparison (MAIC) of teclistamab (tec) versus selinexor-dexamethasone (sel-dex) for the treatment of patients (pts) with tripleclass exposed (TCE) relapsed/refractory multiple myeloma (RRMM). https://meetings.asco.org/abstracts-presentations/207331

Other abstracts about teclistamab are also available on the ASCO and EHA websites: https://meetings.asco.org/abstracts-presentations and https://library.ehaweb.org/

Nizar J. Bahlis Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada

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MagnetisMM Trials: elranatamab Elranatamab is an investigational B-cell maturation antigen (BCMA) CD3-targeted bispecific antibody.

No prior BCMA therapy

2-step priming good (76mg) https://www.myeloma.org/videos/initial-safety-results-magnetismm-3-phase-2-trial-elranatamab-bcma-cd3-bispecific-antibody

Other abstracts about elranatamab are also available on the ASCO and EHA websites: https://meetings.asco.org/abstracts-presentations and https://library.ehaweb.org/

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REGN5458 (BCMAxCD3) The open-label Phase 1/2 dose-escalation trial is investigating REGN5458 (BCMAxCD3)* in patients with relapsed/refractory multiple myeloma who had received at least three prior lines of therapy or were double refractory. All patients had received prior treatment with proteasome inhibitors, immunomodulatory drugs and CD38 antibody treatments.

https://www.myeloma.org/videos/early-deep-durable-responses-regn5458first-human-study-patients-rrmm

*(BCMAxCD3) - Anti-BCMA x Anti-CD3 Bispecific Antibody

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MonumenTAL-1 and TRIMM-2: talquetamab Talquetamab is a first-in-class, investigational T-cell redirecting bispecific antibody targeting both GPRC5D, a novel multiple myeloma target that does not shed over time, and CD3, the T-cell receptor.

Prior anti-BCMA therapy

https://www.myeloma.org/videos/updates-efficacysafety-results-monumental-1talquetamab-rrmm-patients

Other abstracts about talquetamab are also available on the ASCO and EHA websites: https://meetings.asco.org/abstracts-presentations and https://library.ehaweb.org/

https://www.myeloma.org/videos/updated-phase1b-results-talquetamabcombination-daratumumab-treatment-rrmm-patients

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CARTITUDE-1: cilta-cel CARVYKTI™ (ciltacabtagene autoleucel; cilta-cel) is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient’s own T-cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells that express the B-cell maturation antigen (BCMA).

Overall Response Rate (ORR) = 98%

Deep durable responses at 2 years

https://www.myeloma.org/videos/updated-results-phase-1b2-cartitude-1-study-cilta-cel-rrmm-patients

Other abstracts about CARTITUDE trials are also available on the ASCO and EHA websites: https://meetings.asco.org/abstracts-presentations and https://library.ehaweb.org/

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CARTITUDE-2: cilta-cel CARVYKTI™ (ciltacabtagene autoleucel; cilta-cel) is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient’s own T-cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells that express the B-cell maturation antigen (BCMA).

https://www.myeloma.org/videos/updates-clinical-data-cilta-cel-cartitude-2cohort-among-progressive-mm-patients

https://www.myeloma.org/videos/cartitude-2-updated-analyses-ciltacabtageneautoleucel-patients-multiple-myeloma-early

Other abstracts about CARTITUDE trials are also available on the ASCO and EHA websites: https://meetings.asco.org/abstracts-presentations and https://library.ehaweb.org/

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Abecma™ (idecabtagene vicleucel – ide-cel) ABECMA (idecabtagene vicleucel; ide-cel) is a B-cell maturation antigen (BCMA)directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.

Overall Response Rate (ORR) = 83%

Idecabtagene vicleucel (ide-cel) chimeric antigen receptor (CAR) Tcell therapy for relapsed/refractory multiple myeloma (RRMM): Real-world experience. https://meetings.asco.org/abstracts-presentations/207904

Other abstracts about ide-cel are also available on the ASCO and EHA websites: https://meetings.asco.org/abstracts-presentations and https://library.ehaweb.org/

Doris K. Hansen H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL

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Other CAR T Trials

https://www.myeloma.org/videos/updated-study-results-bcmacd19-dualtargeting-car-t-gc012f-rrmm-patients

Conclusion: BCMA/CD19 dual FasT CAR-T GC012F continues to provide deep and durable responses with a favorable safety profile in additional RRMM patients across all dose levels demonstrating a very high MRD-negativity rate, including in patients refractory to anti-CD38, proteasome inhibitors (PI) and immunomodulatory drugs (IMiDs). GC012F is currently being studied in earlier lines of therapy as well as additional indications.

https://www.myeloma.org/videos/phase-1-study-cart-ddbcma-relapsed-orrefractory-multiple-myeloma

Conclusion: To date, CAR T-ddBCMA administration has demonstrated clinical activity, including 100% overall response rate (ORR) with rates of complete response (CR)/stringent complete response (sCR) and ≥ very good partial response (VGPR) of 67% and 88%, respectively. Durable responses beyond 18 months have been observed, including in patients with extramedullary disease (EMD).

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POMALYST® (pomalidomide) combinations 20

Abstract #8012: KPd + dara Overall Response Rate (ORR) = 95%

A phase II study of daratumumab with weekly carfilzomib, pomalidomide, and dexamethasone in relapsed and refractory multiple myeloma. https://meetings.asco.org/abstracts-presentations/207897

Andrew J Yee Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA

To learn more about carfilzomib, pomalidomide, or daratumumab, please visit the IMF Publications page: https://www.myeloma.org/cancer-information-series Publications are available free of charge.

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Abstract #8024: OPTIMISMM Trial

Pomalidomide, bortezomib, and dexamethasone in lenalidomidepretreated multiple myeloma: A subanalysis of OPTIMISMM by frailty. https://meetings.asco.org/abstracts-presentations/207939

Albert Oriol Rocafiguera Hematology Department, Institut Català d’Oncologia, Carretera de Canyet s/n, Barcelona, Spain

To learn more about pomalidomide, bortezomib, lenalidomide, or daratumumab, please visit the IMF Publications page: https://www.myeloma.org/cancer-information-series Publications are available free of charge.

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Risk Factors 23

Abstract #8062: translocation (4;14) 1q+/17 p- added risk

Clinical features of patients with multiple myeloma harboring t(4;14) and impact on long-term survival. https://meetings.asco.org/abstracts-presentations/207924

Nisha Joseph Emory University, Winship Cancer Institute, Atlanta, GA

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Abstract #8064: translocation (11;14) Inferior to standard risk

https://www.myeloma.org/videos/response-rates-among-t11-14-multiple-myeloma-patients-receiving-triplet-induction-therapy

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Abstract #8047: serum FLC ratio FLC ≥ 100 can be OK!

Evaluating serum-free light chain ratio as a biomarker for multiple myeloma. https://meetings.asco.org/abstracts-presentations/207932 Theresia Akhlaghi Department of Internal Medicine, Icahn School of Medicine, Mount Sinai Morningside and West, New York, NY

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Hybrid EHA 2022 (in-person/ online) Total EHA abstracts for 2022 = 2,239 Myeloma Abstracts = 332  Presidential Symposium = 1  Late Breaking = 1  Oral = 25  e-Posters Presentations = 25  Poster Presentations = 165  Publication Only = 115

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Presidential Symposium – S103

https://www.myeloma.org/videos/efficacy-safety-ari0002h-bcma-directed-car-t-rrmm-patients

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EFFICACY AND SAFETY OF ARI0002H, AN ACADEMIC BCMA-DIRECTED CAR-T CELL THERAPY WITH FRACTIONATED INITIAL THERAPY AND BOOSTER DOSE IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA Carlos Fernández de Larrea1, Verónica González-Calle2, Aina Oliver-Caldés1, Valentín Cabañas3, Paula RodríguezOtero4, Marta Español-Rego1, Juan Luis Reguera5, Lucía López-Corral2, Beatriz Martin-Antonio1, Bruno Paiva4, Susana Inogés4, Laura Rosiñol1, Ascensión López-Díaz de Cerio4, Natalia Tovar1, Miriam López-Parra2, Luis Gerardo Rodríguez-Lobato1, Andrés Sánchez-Salinas3, Sara Varea1, Valentín Ortiz-Maldonado1, José Antonio Pérez Simón5, Felipe Prósper4, Manel Juan1, José M. Moraleda3, Maria Victoria Mateos2, Mariona Pascal1, Alvaro Urbano-Ispizua1 (1) Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona; (2) Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Centro de Investigación del Cáncer (IBMCC-USAL, CSIC), Salamanca; (3) Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, University of Murcia, Murcia; (4) Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada (CIMA), IDISNA, CIBERONC Pamplona, Pamplona; (5) Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, University of Sevilla.

Spain

June 11, 2022

There are new strategies for immunotherapy in multiple myeloma

Rodriguez-Lobato et al. Hemato 2020

There are several CAR-T cells for MM in development

Idecabtagene vicleucel

Ciltacabtagene autoleucel

Minimal residual disease (MRD) by Next Generation Flow (NGF)

MRD negative*

Intention to treat

Day +28

Day +100

Month 6

Month 12

21

24

20

16

96%

92%

74%

69%

21/22

24/26

20/25

16/20

70%

80%

67%

53%

Sensitivity: 10-5 to 10-6 *of evaluable samples

Efficacy: Progression-free survival (PFS)

53% at 18 months

Median PFS not reached.

Median follow-up 17.5 months (range 5-23)

Efficacy: Overall survival (OS) 73% at 18 months

Median OS not reached.

Median follow-up 17.5 months (range 5-23)

ATLAS Trial: post-ASCT KRd vs R maintenance KRd superior!

Minimal Residual Disease (MRD) = 47% versus 29% https://www.myeloma.org/videos/atlas-phase-3-randomized-trial-krd-versus-lenalidomide-alone-after-stem-cell-transplant

To learn more about carfilzomib, lenalidomide or dexamethasone, please visit the IMF Publications page: https://www.myeloma.org/cancer-information-series Publications are available free of charge.

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IFM 2018-04: KRd + dara (induction)

https://www.myeloma.org/videos/dara-krd-induction-therapy-high-risk-transplant-eligible-patients-newly-diagnosed-myeloma

To learn more about carfilzomib, lenalidomide, dexamethasone or daratumumab, please visit the IMF Publications page: https://www.myeloma.org/cancer-information-series Publications are available free of charge.

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Modakafusp alfa (TAK-573) Modakafusp alfa (TAK-573) is a first-in-class immunocytokine designed to deliver attenuated interferon alpha-2b to CD38+ cells.

https://www.myeloma.org/videos/updated-results-modakafusp-alfa-tak-573-safety-efficacy-phase-12-study-rrmm-patients Early results for Modakafusp alfa (TAK-573) was presented at ASH 2021: Modakafusp Alfa (TAK-573), an Immunocytokine, in Patients with Relapsed/Refractory Multiple Myeloma; Updated Results from a First-in-Human Phase 1 Study https://www.myeloma.org/videos/modakafusp-alfa-tak-573-immunocytokine-patients-relapsedrefractory-multiple-myeloma-updated

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BLENREP (belantamab mafodotin-blmf) Blenrep (belantamab mafodotin-blmf) is an antibody drug conjugate comprising a humanised BCMA monoclonal antibody conjugated to the cytotoxic agent auristatin F via a non-cleavable linker.

https://www.myeloma.org/videos/dreamm-5-study-blenrep-belantamab-mafodotin-combined-nirogacestat-relapsed-refractory

To learn more about blenrep, please visit the IMF Publications page: https://www.myeloma.org/resource-library/understanding-blenrep Publications are available free of charge.

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BLENREP (belantamab mafodotin-blmf) Blenrep (belantamab mafodotin-blmf) is an antibody drug conjugate comprising a humanised BCMA monoclonal antibody conjugated to the cytotoxic agent auristatin F via a non-cleavable linker.

https://www.myeloma.org/videos/phase-12-study-safety-efficacy-belantamab-mafodotin-rd-newly-diagnosed-transplant-ineligible

To learn more about blenrep, please visit the IMF Publications page: https://www.myeloma.org/resource-library/understanding-blenrep Publications are available free of charge.

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BLENREP (belantamab mafodotin-blmf) Blenrep (belantamab mafodotin-blmf) is an antibody drug conjugate comprising a humanised BCMA monoclonal antibody conjugated to the cytotoxic agent auristatin F via a non-cleavable linker.

https://www.myeloma.org/videos/health-related-quality-life-rrmm-patients-treated-ide-cel-vs-belantamab-mafodotin

To learn more about blenrep, please visit the IMF Publications page: https://www.myeloma.org/resource-library/understanding-blenrep Publications are available free of charge.

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GRIFFIN Trial: VRd + dara (post hoc analysis)

Sustained Minimal Residual Disease (MRD) = 53.7% vs. 20.3% https://www.myeloma.org/videos/analysis-sustained-mrd-negativity-griffin-trial-using-daratumumab-plus-rvd-transplant Updated analysis on the GRIFFIN Trial after 24 months of maintenance therapy was presented at ASH 2021: Daratumumab Plus RVd in Patients with Transplant-Eligible Newly Diagnosed Multiple Myeloma: Updated Analysis of Griffin after 24 Months of Maintenance https://www.myeloma.org/videos/daratumumab-plus-rvd-patients-transplant-eligible-newly-diagnosed-multiple-myeloma-updated

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IFM 2018-02: ixazomib + dara

https://www.myeloma.org/videos/ixazomib-daratumumab-without-dex-i-dara-elderly-frail-relapsedrefractory-multiple-myeloma

To learn more about ixazomib or daratumumab, please visit the IMF Publications page: https://www.myeloma.org/cancer-information-series Publications are available free of charge.

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Sub-Q isatuximab + Pd

https://www.myeloma.org/videos/interim-phase-1b-study-results-isatuximab-pd-subcutaneous-administration-rrmm-patients

To learn more about isatuximab or pomalidomide, please visit the IMF Publications page: https://www.myeloma.org/cancer-information-series Publications are available free of charge.

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Time for Questions!

If you have a question that does not get answered today, please contact our Infoline at 800-452-CURE (2873) US & Canada, 1-818-487-7455, or email infoline@myeloma.org

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Thank you to our sponsors!

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