How to incorporate novel therapies into the treatment paradigm for early RRMM?

The Multiple Myeloma Hub spoke with Rakesh Popat, University College Hospital, London, UK. We asked, How to incorporate novel therapies into the treatment paradigm for early relapsed/refractory multiple myeloma (RRMM)?

In this interview, Dr Popat discussed the evolving treatment landscape for early RRMM, highlighting the integration of novel agents, particularly B-cell maturation antigen (BCMA)-directed therapies including belantamab mafodotin. The discussion outlined both the efficacy and toxicities associated with belantamab mafodotin combination regimens, emphasizing the importance of adapted dosing schedules. Popat also discussed strategies for sequencing BCMA-directed therapies, including chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies.

Key learnings

• The treatment paradigm for early RRMM is evolving rapidly due to the development of several novel therapies.

• CD38-directed regimens, such as those including daratumumab with bortezomib, carfilzomib, or pomalidomide, remain the current standard-of-care treatment in early relapse.

• BCMA-targeted therapies were initially developed for the treatment of heavily pretreated MM but are now being investigated in earlier lines of relapse.

• Belantamab mafodotin, a BCMA-directed antibody–drug conjugate, has demonstrated promising efficacy in combination with either bortezomib + dexamethasone or pomalidomide + dexamethasone in the phase III DREAMM-7 (NCT04246047) and DREAMM-8 (NCT04484623) studies, respectively.

• Belantamab mafodotin is currently approved as part of a combination therapy in the UK for patients who have received at least one prior line of therapy, with more global approvals anticipated.

• Belantamab mafodotin is associated with ocular toxicities, which necessitate individualized dose scheduling and monitoring.

• In clinical practice, dosing for belantamab mafodotin is often modified to every 6–8 weeks during the initial treatment phase, followed by 12-week intervals during maintenance, to reduce toxicity without sacrificing efficacy.

• The future treatment landscape in early RRMM includes the potential integration of additional BCMA-targeted therapies such as bispecific antibodies and CAR T-cell therapies.

• CAR T-cell therapies are increasingly considered in earlier lines, including at the first relapse, to take advantage of increased T-cell fitness.

• Sequential use of BCMA-targeted therapies is feasible; however, based on real-world data, a washout period of approximately 6 months is suggested between treatments to mitigate resistance and optimize efficacy.¹

• Personalized treatment sequencing and timing will be critical as more BCMA-directed agents become available in earlier treatment lines.

This educational resource is independently supported by GSK. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.