Dr Hashmi on the Identification of Candidates for CAR T-Cell Therapy in Early R/R Myeloma

High-risk disease biology tends to outrun the benefit of CAR T-cell therapy the longer it’s delayed, which is the core argument for moving CAR T-cell therapy into earlier lines in these patients, rather than saving it for later lines.

Hamza Hashmi, MD, an assistant attending physician at Memorial Sloan Kettering Cancer Center, discussed strategies to identify optimal patients with relapsed/refractory multiple myeloma as candidates for CAR T-cell therapy in the early relapse setting, along with how disease risk status should shape the timing of treatment.

The discussion follows the movement of CAR T-cell therapy into earlier lines of care in multiple myeloma. In April 2024, the FDA approved ciltacabtagene autoleucel (cilta-cel; Carvykti) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 1 prior line of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), and who are refractory to lenalidomide (Revlimid). On the same day, the regulatory agency also approved idecabtagene vicleucel (ide-cel; Abecma) for the treatment of adult patients with relapsed or refractory multiple myeloma after 2 or more prior lines of therapy, including an IMiD, a PI, and an anti-CD38 monoclonal antibody.

The patients most often considered ideal referrals for early CAR T-cell therapy are those with functionally high-risk multiple myeloma, meaning disease that is primary refractory or that relapses within 18 months of frontline therapy, Hashmi said. The logic, he explained, is that these patients stand to gain the most from a highly effective, deep-response therapy delivered early, because their disease biology predicts poor responsiveness to CAR T-cell therapy in later lines of therapy following other treatment courses.

However, risk status cuts both ways depending on the line of therapy, according to Hashmi. In earlier lines, high-risk disease is where the efficacy of CAR T-cell therapy over standard-of-care (SOC) therapy is most pronounced, and the modality has shown superior efficacy in earlier lines across functionally high-risk patients, he noted. In later-line, high-risk patients, by contrast, outcomes with CAR T-cell therapy are less favorable.

The case for earlier intervention with CAR T-cell therapy is not limited to high-risk disease, Hashmi continued. Updated follow-up data from the phase 3 CARTITUDE-4 trial (NCT04181827) showed that patients treated with cilta-cel (n = 208) achieved an estimated 30-month PFS rate of 59.4% (95% CI, 52.3%-65.7%) compared with 25.7% (95% CI, 19.8%-31.9%) for patients treated with SOC (n = 211). In another analysis presented at the 2025 ASH Annual Meeting, findings showed that patients with standard-risk disease in the as-treated population (n = 59) experienced a 30-month PFS rate of 80.5%; when including patients with 1q gains or amplifications (n = 105), this rate was 71.7%. These outcomes point toward a potential cure for standard-risk patients, Hashmi explained.

He concluded by explaining that CAR T-cell therapy should be considered not only for patients with functionally high-risk disease at early relapse, but also for patients with standard-risk disease.