Ep 1. The New Algorithm for Second-Line Treatment of Multiple Myeloma
Rohit Gosain, MD
Rahul Gosain, MD, MBA
S. Vincent Rajkumar, MD
Rafael Fonseca, MD
Beth Faiman, CNP, PhD
Key Points
- The growth of quadruplet regimens for frontline treatment of multiple myeloma generated a need for novel treatment options for relapsed or refractory patients.
- Chimeric antigen receptor (CAR) T-cell therapy and bispecific antibody–based regimens have emerged as the new standard of care for relapsed or refractory multiple myeloma in the second line.
Cohosts of the Oncology Brothers podcast, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, met with Beth Faiman, CNP, PhD, of Cleveland Clinic; Rafel Fonseca, MD, of Mayo Clinic; and S. Vincent Rajkumar, MD, of Mayo Clinic, to review the treatment landscape for relapsed or refractory multiple myeloma. During the discussion, Dr. Rajkumar provided an overview of the rapidly evolving second-line treatment paradigm.
Historically, triplet regimens like daratumumab, lenalidomide, and dexamethasone were the standard treatments for relapsed or refractory multiple myeloma after frontline therapy. However, the adoption of daratumumab and lenalidomide–containing regimens in the frontline setting produced a need for new options in the second line.
Initially, CAR T-cell therapy with ciltacabtagene autoleucel emerged to fill this gap. More recently, trials showed bispecific antibody–based regimens significantly improved outcomes compared with triplets in the second-line setting. Specifically, the MajesTEC-3 trial showed teclistamab plus daratumumab outperformed the investigator’s choice of standard triplet, and the FDA approved the combination for second-line therapy on March 5, 2026. In addition, the MajesTEC-9 trial showed teclistamab monotherapy also improved survival compared with standard therapies.
Based on the available data, CAR T-cell or bispecific–based therapy should be prioritized in second-line treatment of relapsed or refractory multiple myeloma. However, if tolerability or availability are obstacles, falling back on standard triplets is a valid option, said Dr. Rajkumar.