Dr Hansen on the Integration of CAR T-Cell Therapy Into Earlier Myeloma Treatment Lines

As we move [CAR T-cell therapy] earlier in the disease course, whether that be idecabtagene vicleucel or cilta-cel, hopefully we are going to see better responses [and] a larger potential for a cure or functional cure in these patients, which is incredible.

Doris Hansen, MD, an associate member in the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center, discussed the ongoing integration of CAR T-cell therapy into earlier lines of treatment for multiple myeloma, spotlighting long-term data from cohort A of the phase 2 CARTITUDE-2 trial (NCT04133636) evaluating ciltacabtagene autoleucel (cilta-cel; Carvykti).

In the phase 1b/2 CARTITUDE-1 trial (NCT03548207), which enrolled heavily pretreated patients and supported the initial FDA approval of cilta-cel in February 2022 for patients who have received at least 4 prior lines of therapy, Hensen explained that approximately one-third of patients treated achieved what she described as a functional cure. New data from CARTITUDE-2 cohort A, presented at the 23rd International Myeloma Society Annual Meeting, focused on patients who had received 1 to 3 prior lines of therapy, she noted, similar to the phase 3 CARTITUDE-4 trial (NCT04181827), where patients received a prior proteasome inhibitor and were lenalidomide (Revlimid) refractory.

Findings from cohort A of CARTITUDE-2 showed that among evaluable patients (n = 20), 50% were alive and progression free at 5 years. At a median follow-up of 60.7 months (range, 3.3-63.1), the 5-year progression-free survival rate was 54.2% (95% CI, 30.3%-73.0%), and the 5-year overall survival rate was 69.2% (95% CI, 43.8%-84.9%).

Hansen said the earlier that CAR T-cell therapies, such as cilta-cel or idecabtagene vicleucel (Abecma), are given in the disease course, the better the outcomes. Patients with high-risk disease have the greatest need, but those with standard-risk disease may benefit even more, she explained.

However, access remains a barrier for these approved CAR T-cell therapies, Hansen said, noting that few patients are referred for CAR T-cell therapy in the early relapse setting. The process includes apheresis and lymphodepletion, and patients must stay away from home with a caregiver for at least 2 to 4 weeks.

Still, products are being manufactured faster, bridging therapies are more effective, and manufacturers offer patient assistance programs, she noted. The FDA has also removed the risk evaluation and mitigation strategy (REMS) requirements for approved CAR T-cell therapies, shortening the driving restriction from 8 weeks to 2 weeks and the required stay near the treatment center from 4 weeks to 2 weeks, Hansen concluded, noting that ongoing work is aiming to continue to improve CAR T-cell therapy access for patients.