Dr Fonseca on Treatment Selection at First Relapse in Multiple Myeloma

In my mind, there is no question that any patient who is experiencing a first relapse in 2026 should be [receiving] either CAR T[-cell therapy] or a bispecific antibody.

Rafael Fonseca, MD, a professor of medicine, chief innovation officer, a consultant in the Division of Hematology/Oncology in the Department of Internal Medicine, and director for Innovation and Transformational Relationships at Mayo Clinic, discussed how the growing body of clinical trial data is reshaping treatment selection at first relapse for patients with multiple myeloma.

Reaching consensus on the optimal approach at first relapse has been difficult, and that difficulty is likely to persist for some time due to positive clinical trials evaluating a variety of treatment approaches in this setting, Fonseca said. Given what is now known from recently published and presented clinical trials, he said that all patients experiencing a first relapse in 2026 should be treated with either CAR T-cell therapy or a bispecific antibody–based regimen.

Although combination regimens comprising anti-CD38 antibodies, proteosome inhibitors, and immunomodulatory drugs for myeloma have proven useful, these combinations now fall short against the efficacy of CAR T-cell therapy and bispecific antibodies, according to Fonseca. He added that the myeloma field is still gradually adopting these newer approaches; in his view, only a small fraction of hematology practices have fully shifted to this approach.

Fonseca cautioned against reserving CAR T-cell therapies and bispecific antibodies for later lines. The more scientifically interesting question, he said, is whether a bispecific antibody or CAR T-cell therapy should be used first. Although clinical trials have produced excellent results with both, and the nuances between these classes of drugs warrant lengthy discussion, he said he favors administering CAR T-cell therapy before a bispecific antibody for a number of reasons. Even so, Fonseca concluded, a significant lack of consensus on sequencing is likely to remain for the foreseeable future.