Dr Berdeja on the Evolving Use of CAR T-Cell Therapy in Multiple Myeloma

Jesus Berdeja, MD, director, Multiple Myeloma Research, Tennessee Oncology, discusses the evolving guidelines regarding the use of CAR T-cell therapy in patients with multiple myeloma.

The current guidelines for CAR T-cell therapy administration in patients with multiple myeloma state that patients must have received a minimum of 4 prior lines of therapy, Berdeja begins. However, notable advancements have emerged through 2 phase 3 trials: the KarMMa-3 (NCT03651128) and CARTITUDE-4 (NCT04181827) trials, which evaluated idecabtagene vicleucel (Abecma; ide-cel) and ciltacabtagene autoleucel (cilta-cel; Carvykti), respectively, in earlier stages of treatment, he explains. The results of these trials have demonstrated the superiority of CAR T-cell therapy compared with other multiple myeloma therapies, according to Berdeja. KarMMa-3 enrolled patients who had received 2 to 4 prior lines of therapy, most of whom had been exposed to anti-CD38 treatments. Contrarily, CARTITUDE-4 evaluated patients who had received 1 to 3 prior lines of therapy, with a lower proportion having been previously exposed to anti-CD38 therapies, Berdeja emphasizes. Both trials revealed the effectiveness of CAR T-cell therapy over the standard treatment regimen, he states.

Oncologists anticipate that the FDA will revise the indication for CAR T-cell therapies for patients with multiple myeloma, potentially moving them into earlier stages of treatment, Berdeja expands. The specific indications remain to be defined, but there is a possibility that the stipulation regarding the number of prior lines of therapy may be lifted, he explains. This development would be important because it would address the concerns of many patients who may struggle to endure 4 lines of therapy before accessing CAR T-cell treatment, especially when CAR T-cell therapy has proven to be a superior regimen, Berdeja says.

Moreover, ongoing research efforts are now focusing on incorporating CAR T-cell therapies and bispecific antibodies into the frontline setting for patients with multiple myeloma, Berdeja continues. The primary population of interest in this research includes high-risk patients who have historically not responded favorably to standard therapies, Berdeja says. Furthermore, randomized phase 3 trials are beginning to explore the possibility of using CAR T-cell therapies beyond the high-risk population in patients who are either eligible or ineligible for transplantation.

Considering these developments, it is possible that in coming years, CAR T-cell therapies and bispecific antibodies could become integrated into the frontline treatment setting for patients with multiple myeloma, potentially reshaping the therapeutic landscape, Berdeja concludes.