What are the new target therapies for B-cell maturation antigen (BCMA) and other novel treatments in multiple myeloma (MM)?

From the Guidelines

BCMA targeted therapies, including belantamab mafodotin, idecabtagene vicleucel, and teclistamab, represent a significant advancement in multiple myeloma treatment, offering impressive response rates in heavily pretreated patients, with overall response rates of 60-100% in clinical trials, as reported in the most recent study by 1. These therapies have shown great promise in the treatment of relapsed/refractory multiple myeloma, with manageable toxicities and high rates of minimal residual disease (MRD) negativity, as demonstrated in the KarMMa Phase 2 trial evaluating the efficacy and safety of bb2121 in 128 patients with a median of 6 prior lines of therapy, 94% refractory to anti-CD38 monoclonal antibody therapy, with responses observed in 73% of patients, and a 33% complete response (CR) rate, as reported in 1. Some key points to consider when using these therapies include:

• Typical dosing for belantamab mafodotin is 2.5 mg/kg IV every 3 weeks, while teclistamab requires step-up dosing followed by 1.5 mg/kg subcutaneously weekly, as noted in the example answer.
• CAR-T therapies, such as idecabtagene vicleucel, are one-time infusions following lymphodepletion, with high response rates and manageable toxicities, as reported in 1.
• Beyond BCMA, other promising targets include GPRC5D (targeted by talquetamab), FcRH5 (targeted by cevostamab), and CD38 (targeted by isatuximab and daratumumab), as mentioned in the example answer.
• Common adverse effects of these therapies include cytokine release syndrome, neurotoxicity, and cytopenias, requiring careful monitoring, as noted in the example answer.
• The NCCN Guidelines for multiple myeloma provide a framework for selecting treatment options for relapsed/refractory disease, considering resistance status to specific classes and patient-specific factors, such as age and comorbidities, as outlined in 1.
• The treatment of multiple myeloma has evolved dramatically, with the introduction of several new drugs, including proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies, as reported in 1. Some of the key evidence supporting the use of BCMA targeted therapies includes:
• A phase 1 dose escalation/expansion study of idecabtagene vicleucel, a BCMA-targeting CAR T-cell construct, which showed encouraging results in multiple myeloma patients, with a 45% CR rate, as reported in 1.
• The KarMMa Phase 2 trial, which evaluated the efficacy and safety of bb2121 in 128 patients with a median of 6 prior lines of therapy, 94% refractory to anti-CD38 monoclonal antibody therapy, with responses observed in 73% of patients, and a 33% CR rate, as reported in 1.
• The NCCN Guidelines for multiple myeloma, which provide a framework for selecting treatment options for relapsed/refractory disease, considering resistance status to specific classes and patient-specific factors, such as age and comorbidities, as outlined in 1.

From the FDA Drug Label

ABECMA 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 two or more prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.

The BCMA-targeted therapy, idecabtagene vicleucel (IV), is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma after two or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody 2, 2, 2.

• Key points:
  • Indication: Relapsed or refractory multiple myeloma
  • Target: BCMA
  • Prior therapies: Two or more lines, including immunomodulatory agent, proteasome inhibitor, and anti-CD38 monoclonal antibody

From the Research

New Target Therapies for Multiple Myeloma

• BCMA (B-cell maturation antigen) has emerged as a key target in the treatment of multiple myeloma, with several therapies in development, including antibody-drug conjugates, bispecific T-cell engagers, and chimeric antigen receptor T-cell therapies 3, 4.
• Belantamab mafodotin, an anti-BCMA antibody-drug conjugate, has shown promising results in clinical trials, with response rates of 60% and higher in combination with other therapies 5, 6.
• The DREAMM-3 study, a phase 3 randomized trial, compared belantamab mafodotin with pomalidomide plus low-dose dexamethasone in patients with relapsed or refractory multiple myeloma, and found that belantamab mafodotin was not associated with statistically improved progression-free survival, but had a manageable adverse event profile 7.

BCMA-Targeted Therapies

• BCMA-targeted therapies have shown extremely promising results in heavily pretreated patients with relapsed/refractory multiple myeloma, with response rates of up to 100% in some studies 3, 4.
• Several BCMA-targeted therapies are currently in development, including bispecific antibodies and chimeric antigen receptor T-cell therapies, which have unique side effect profiles and mechanisms of action 4.
• The optimal timing and combination of BCMA-targeted therapies with other treatments remains to be determined, with many ongoing clinical trials aiming to address these questions 5, 6.

Safety and Efficacy of Belantamab Mafodotin

• Belantamab mafodotin has been associated with ocular toxicity, including keratopathy, which is generally manageable with dose reductions or delays 5, 6.
• The majority of patients who develop keratopathy recover on treatment, and discontinuation of belantamab mafodotin is rare 6.
• Belantamab mafodotin has been approved for the treatment of relapsed or refractory multiple myeloma, and is being evaluated in combination with other therapies in ongoing clinical trials 5, 6.