EXPANDING THE HORIZON IN RELAPSED OR REFRACTORY MULTIPLE MYELOMA

Relapsed or refractory multiple myeloma is a complex disease, the treatment of which would benefit from further study and investigation. There remains a critical need for new approaches in later lines.1

BCMA-Targeted Strategy Challenges of Treating Multiple Myeloma

Treating advanced cases in relapsed or refractory multiple myeloma remains a significant challenge

There remains a need for improved treatment options for patients with relapsed or refractory multiple myeloma, including those who have progressed following treatment with multiple classes of drugs.

As multiple myeloma progresses, relapses become more aggressive with each line of therapy, and remissions become progressively shorter.1-7

Tumor Burden - Time Chart Tumor Burden - Time Chart

Triple class refractory disease occurs when patients relapse on or are refractory to one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody.8-11

Proteasome Inhibitors
Immunomodulatory Agents
Anti-CD38
Monoclonal Antibodies

The complex nature of relapsed or refractory multiple myeloma requires specific treatment solutions.

Patients with triple-class refractory disease tend to have more progressive disease, high-risk cytogenetic profiles, fewer treatment options, and poorer prognoses.8,11-13

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Watch this video about BCMA targeting in relapsed or refractory multiple myeloma

BCMA is an exciting targeting option for the potential treatment of relapsed or refractory multiple myeloma

B-cell maturation antigen (BCMA) is a cell-surface protein predominantly expressed on terminally differentiated B cells, that regulates B-cell proliferation, survival, and maturation and differentiation into plasma cells.14-18

Multiple BCMA-targeted therapies are being studied across the industry

These treatments all work in different ways to target BCMA.19-24 T cell redirecting bispecific antibodies, for example, work by binding to BCMA molecules on the surface of multiple myeloma cells and CD3 molecules on the surface of the patient's T cells. Once bound to both cells, the T cell is in proximity to the multiple myeloma cell and can trigger myeloma cell death.25

IT IS IMPORTANT TO STAY INFORMED ABOUT NEW TARGETS AND THERAPEUTIC STRATEGIES UNDER INVESTIGATION.

Investigations are currently underway for the development of new BCMA-targeting therapies across a broad range of therapeutic classes, including19-24:

ANTIBODY-DRUG
CONJUGATES
CAR-T
BISPECIFIC
ANTIBODIES
CAR-NK
TRISPECIFIC
ANTIBODIES

Janssen Biotech, Inc., is committed to investigating T cell redirecting bispecific antibodies to help address the unmet need for patients with relapsed or refractory multiple myeloma26

Janssen Biotech, Inc., is also investigating GPRC5D, a transmembrane protein highly expressed on plasma cells with minimal expression in healthy tissues, as a multiple myeloma target.27

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  1. Delforge, M. (2015) Treatment of relapsed multiple myeloma. In: Mohty M, Harousseau J-L, (eds). Handbook of Multiple Myeloma. https:doi.org/10.1007/978-3-319-18218-6_5. Springer International Publishing.
  2. Kumar SK, Therneau TM, Gertz MA, et al. Clinical course of patients with relapsed multiple myeloma. Mayo Clin Proc. 2004;79(7):867-874.
  3. Paccagnella A, Chiarion-Sileni V, Soesan M, et al. Second and third responses to the same induction regimen in relapsing patients with multiple myeloma. Cancer. 1991;68(5):975-980.
  4. Drewinko B, Alexanian R, Barlogie B, et al. The growth fraction of human myeloma cells. Blood. 1981;57(2):333-338.
  5. Borello I. Can we change the disease biology of multiple myeloma? Leuk Res. 2012;36(S1):S3-S12.
  6. Keats JJ, Chesi M, Egan JB, et al. Clonal competition with alternating dominance in multiple myeloma. Blood. 2012;120(5):1067-1076.
  7. Sonneveld P. Management of multiple myeloma in the relapsed/refractory patient. Hematology Am Soc Hematol Educ Program. 2017;1:508-517.
  8. Goldsmith SR, Fiala MA, Schroeder TM, et al. DCEP and bendamustine/prednisone as salvage therapy for quad- and penta-refractory multiple myeloma. Ann Hematol. 2020;99(5):1041–1048.
  9. Vogl DT, Dingli D, Cornell RF, et al. Selective inhibition of nuclear export with oral selinexor for treatment of relapsed or refractory multiple myeloma. J Clin Oncol. 2018;36(9):859-866.
  10. Shah N, Crivera C, Mehra M, et al. Treatment patterns in multiple myeloma: Real-world experience of the triple-class exposed (TCE) patient. Poster presented: American Society of Clinical Oncology Annual Meeting. May 29-June 2, 2020. Chicago, IL.
  11. Ghandi UH, Cornell RF, Lakshman A, et al. Outcomes of patients with multiple myeloma refractory to CD-38-targeted monoclonal antibody therapy. Leukemia. 2019;33(9)2266-2275.
  12. Dhanasiri S, Hollier-Hann G, Stothard C, et al. Treatment patterns and outcomes in triple-class exposed patients with relapsed and refractory multiple myeloma: findings from the multinational ITEMISE Study. Clin Ther. 2021;43(11):1983-1996.e3.
  13. Jagannath S, Lin Y, Goldschmidt H, et al. KarMMa-RW: A study of real-world treatment patterns in heavily pretreated patients with relapsed and refractory multiple myeloma (RRMM) and comparison of outcomes to KarMMa. J Clin Oncol. 2020;38(15_suppl):8525-8525.
  14. Laâbi Y, Gras MP, Carbonnel F, et al. A new gene, BCM, on chromosome 16 is fused to the interleukin 2 gene by a t(4;16)(q26;p13) translocation in a malignant T-cell lymphoma. EMBO J. 1992;11(11):3897-3904.
  15. Laâbi Y, Gras M-P, Brouet J-C, et al. The BCMA gene, preferentially expressed during B lymphoid maturation, is bidirectionally transcribed. Nucleic Acids Res. 1994;22(7):1147-1154.
  16. Thompson JS, Schneider P, Kalled SL, et al. BAFF binds to the tumor necrosis factor receptor-like molecule B cell maturation antigen and is important for maintaining the peripheral B cell population. J Exp Med. 2000;192(1):129-135.
  17. O’Connor BP, Raman VS, Erickson LD, et al. BCMA is essential for the survival of long-lived bone marrow plasma cells. J Exp Med. 2004;199(1):91-97.
  18. Novak AJ, Darce JR, Arendt BK, et al. Expression of BCMA, TACI and BAFF-R in multiple myeloma: a mechanism for growth and survival. Blood. 2004;103(2):689-694.
  19. Yu B, Jiang T, Liu D. BCMA-targeted immunotherapy for multiple myeloma. J Hematol Oncol. 2020;13:125.
  20. MEDI2228 in subjects with relapsed/refractory multiple myeloma (MEDI2228). ClinicalTrials.gov identifier NCT03489525. Updated February 14, 2022. Accessed March 10, 2022. https://clinicaltrials.gov/ct2/show/NCT03489525
  21. Study of bb21217 in multiple myeloma. ClinicalTrials.gov identifier: NCT03274219. Updated March 18, 2021. Accessed March 31, 2022. https://www.clinicaltrials.gov/ct2/show/NCT03274219
  22. Clinical research of adoptive BCMA CAR-NK cells on relapsed/refractory MM. ClinicalTrials.gov identifier: NCT03940833. Updated May 7, 2019. Accessed March 31, 2022. https://www.clinicaltrials.gov/ct2/show/NCT03940833
  23. Assessment of AMG 420 in subjects with relapsed and/or refractory multiple myeloma (AMG420). ClinicalTrials.gov identifier: NCT03836053. Updated December 10, 2021. Accessed March 31, 2022. https://clinicaltrials.gov/ct2/show/NCT03836053
  24. Gantke T, Weichel M, Herbrecht C, et al. Trispecific antibodies for CD16A-directed NK cell engagement and dual-targeting of tumor cells. Protein Eng Des Sel. 2017;30(9):673-684.
  25. Suurs FV, Lub-de Hooge MN, de Vries EGE, de Groot DJA. A review of bispecific antibodies and antibody constructs in oncology and clinical challenges. Pharmacol Ther. 2019;201:103-119.
  26. Our Vision: The Elimination of Cancer. Johnson & Johnson Services, Inc. Accessed March 31, 2022. https://www.jnj.com/oncology
  27. Dose escalation study of talquetamab in participants with relapsed or refractory multiple myeloma. ClinicalTrials.gov identifier: NCT03399799. Updated March 25, 2022. Accessed April 1, 2022. https://clinicaltrials.gov/ct2/show/NCT03399799