Dr Fonseca on Selecting a Treatment in Relapsed/Refractory Myeloma

"The most pressing question we have right now is the use of CAR T-cell therapy for patients at their first relapse. I don’t believe there is uniformity in opinion in terms of what to do because some [clinicians] still want to see more data and to better understand the risk of certain toxicities, particularly the long-term toxicities."

Rafael Fonseca, MD, director for Innovation and Transformational Relationships, at Mayo Clinic, discussed factors that he considers when selecting a treatment for patients with relapsed/refractory multiple myeloma.

In prior years, understanding the entire possible sequence of therapy was a focus with respect to treatment selection, but now the priority has become selecting the best treatment possible, Fonseca began. This is partially due to the benefit of treatment and duration of response decreasing with each subsequent line of therapy, he continued.

Additionally, with each line of therapy that is given, there is a portion of patients who do not go on to receive more treatment, Fonseca noted. This is frequently due to disease progression, death, or treatment toxicity, he said. Therefore, although reserving certain therapies for later seems logical, this rate of attrition must be factored into treatment selection decisions, he said.

Fonseca noted that a major question that remains is the role of CAR T-cell therapies for patients at their first relapse. In April 2024, the FDA expanded the approval of ciltacabtagene autoleucel (cilta-cel; Carvykti) to include patients with relapsed/refractory multiple myeloma who received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide (Revlimid). The regulatory decision made the agent the first BCMA-targeted therapy approved for the treatment of patients with multiple myeloma as early as first relapse. Data from the phase 3 CARTITUDE-4 study (NCT04181827), which supported the approval, demonstrated that patients who received cilta-cel experienced a 59% reduction in the risk of disease progression or death compared with standard-of-care treatments.

Some investigators are still waiting for additional data and want to better understand the potential toxicities of CAR T-cell agents in the first-relapse setting, Fonseca said. However, the benefit of these therapies in this setting, particularly in terms of progression-free survival and patient quality of life, are notable, he concluded.