Emerging Treatment Landscape for Multiple Myeloma

A common theme among many of the sessions presented at the ONS 2023 Congress was the continually emerging treatment landscape for patients with multiple myeloma (MM). “New and Emerging Therapies in Multiple Myeloma: Case Studies for Nurses,” presented by Beth Faiman, Amy Pierre, Tiffany Richards, and Charise Gleason, and “Myeloma: Treating Blood Cancer as a Chronic Disease,” presented by Dr Krina Patel and Rhonda Hewitt, detailed new and emerging therapies for patients with newly diagnosed and relapsed/refractory disease across the multiple myeloma (MM continuum. For patients with newly diagnosed multiple myeloma (NDMM), common regimens consist of 3 to 4 therapies including lenalidomide, bortezomib, and dexamethasone (RVd); carfilzomib, lenalidomide, and dexamethasone; ixazomib, lenalidomide, and dexamethasone; bortezomib, cyclophosphamide, and dexamethasone; and bortezomib, melphalan, and prednisone with or without the addition or daratumumab (dara).

The phase 3 GRIFFIN trial determined that, in patients with NDMM ineligible for transplant, the addition of dara to RVd significantly improved overall response rate (ORR) and depth of response, including minimal residual disease negativity, while the MAIA trial demonstrated a progression-free survival (PFS) benefit with the addition of dara to Rd. In patients with early-relapse MM treated with 1 to 3 prior lines of therapy, many FDA-approved agents are utilized in a variety of combination treatment regimens, with clinical trials continuing to evolve treatment paradigms and inform best practices with new data. The IKEMA trial demonstrated a PFS and depth of response benefit with the addition of isatuximab (Isa) to Kd in patients with early and late relapse, while the ICARIA-MM trial improved ORR and PFS with Isa-Pd versus Pd alone, adding another anti-CD38 agent as a therapeutic option.

There are many novel therapies in development that continue to broaden the therapeutic landscape in patients with relapsed/refractory MM (RRMM). Elotuzumab is an anti–SLAMF-7 antibody that can be used in combination with Pd in patients who have utilized ≥2 prior lines of therapy and with Rd in patients with 1 to 3 prior therapies. Selinexor (X) is an oral selective inhibitor of nuclear export that can be used with Vd in patients with ≥1 prior therapy and as Xd in patients with ≥4 prior therapies. B-cell maturation antigen (BCMA) has become a therapeutic target in MM of increasing interest and is expressed on nearly all MM cells. Numerous modalities newly approved and in development for the treatment of patients with RRMM targeting BCMA include antibody–drug conjugates, chimeric antigen receptor T cells (CAR-T cells), and bispecific antibodies.

There are 2 FDA-approved CAR-T cell therapies targeting BCMA in MM, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). The phase 3 KarMMa-3 trial improved PFS and overall survival with ide-cel compared to standard of care in 386 patients with RRMM who received 1 to 3 prior lines of therapy, while the CARTITUDE-2 trial demonstrated a benefit with cilta-cel in patients with early-relapse MM after initial therapy and in patients previously treated with noncellular anti-BCMA therapy. Bispecific antibodies are another therapeutic class targeting BCMA using a novel mechanism of action; they bind CD3 on T cells and BCMA on plasma cells mediating T-cell activation and lysis of BCMA-expressing MM cells. In the session “Learn More About a Treatment in Relapsed/Refractory Multiple Myeloma,” Mary Steinbach discussed clinical data on the bispecific antibody teclistamab, the only FDA-approved bispecific antibody for RRMM after ≥4 prior lines of therapy. The MajesTEC-1 phase 1/2 study demonstrated durable responses in patients with RRMM treated with teclistamab which deepened over time. There are other bispecific antibodies in development targeting BCMA as well as GPRC5D and FcRH5.