What is the rationale for treating early RRRM with targeted therapies?

The Multiple Myeloma Hub spoke to Sagar Lonial, Winship Cancer Institute of Emory University, Atlanta, US. We asked, What is the rationale for treating early relapsed/refractory multiple myeloma (RRMM) with targeted therapies?

In this interview, Lonial discusses how the treatment landscape for early RRMM has changed over time, impacting the effectiveness of standard of care therapies and leading to an increased interest in new targeted approaches, such as chimeric antigen receptor (CAR) T-cell therapies, bispecific antibodies, and antibody–drug conjugates. Lonial outlines the latest regulatory updates and available options for patients who are ineligible for or unable to access all advanced therapies.

Key learnings

• The treatment landscape for early relapse has evolved in recent years, in part due to the movement of anti-CD38 monoclonal antibodies (mAbs) into induction and maintenance therapies.
• CD38-based mAb salvage therapies were typically employed in early relapse but may now be inappropriate in some patients with prior exposure to anti-CD38 in the newly diagnosed setting.
• Targeted therapies, including CAR T-cell therapies, bispecific antibodies, and antibody–drug conjugates, are effective in the heavily pretreated population and are now being investigated in earlier lines of therapy, including in early RRMM.
• Regulatory approvals of CAR T-cell therapies, including ciltacabtagene autoleucel in the second-line and idecabtagene vicleucel in the third-line, provide more opportunities for treatment-free intervals in early relapse.^1,2
• Antibody–drug conjugates, such as belantamab mafodotin, show promising efficacy in early relapse, particularly when combined with immunomodulatory agents or proteasome inhibitors, as seen in the phase III DREAMM-7 (NCT04246047) and DREAMM-8 (NCT04484623) studies.
• Belantamab mafodotin provides an important option, particularly in those patients who are not eligible for or cannot access treatment with CAR T-cell therapies or bispecific antibodies.
• Novel targeted therapies are transforming the treatment paradigm in early relapse, providing more effective options for patients and allowing personalized treatment selection based on prior treatment and patient and disease characteristics.

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.