Dr Munshi on the Future of CAR T-Cell Therapy in Multiple Myeloma

Nikhil C. Munshi, MD, director, Basic and Correlative Science, the Jerome Lipper Multiple Myeloma Center, Kraft Family Chair, director, Multiple Myeloma Immune Effector Cell Therapy, senior physician, Dana-Farber Cancer Institute; professor, medicine, Harvard Medical School, discusses potential future directions for ciltacabtagene autoleucel (cilta-cel; Carvykti) and other CAR T-cell therapies in patients with multiple myeloma.

The phase 3 CARTITUDE-4 trial (NCT04181827) evaluated the efficacy and safety of cilta-cel vs physician’s choice of standard treatment in patients with lenalidomide (Revlimid)–refractory multiple myeloma who had received between 1 and 3 prior lines of therapy. At a median follow-up of 15.9 months, the median progression-free survival (PFS) was not reached in the patients who received cilta-cel vs 11.8 months in those who received standard of care (SOC). The 12-month PFS rates were 75.9% and 48.6% in the cilta-cel and SOC arms, respectively. In addition, the overall response rates were 84.6% vs 67.3% in the cilta-cel and SOC arms, respectively, including 73.1% and 21.8% of patients, respectively, who achieved a complete response or better. Furthermore, 60.6% of patients in the cilta-cel arm achieved minimal residual disease negativity vs 15.6% of patients in the SOC arm. CARTITUDE-4 demonstrated the efficacy of cilta-cel in earlier treatment lines, reflecting where the next advances in the management of multiple myeloma are likely to occur, Munshi says.

Ongoing studies are also investigating whether cilta-cel can provide deep and durable responses comparable to the responses seen with transplant in patients with multiple myeloma, Munshi notes. If these studies are positive, eligible patients may receive CAR T-cell therapy as a SOC rather than transplant.

CAR T-cell therapy has also generated beneficial outcomes in older patient populations and may soon become the SOC for these patients as well, Munshi explains. Since CAR T-cell therapy is better tolerated than transplant, instead of stopping multiple myeloma treatment at 70 years of age, patients can safely receive this therapy at older ages, as indicated in clinical trials such as CARTITUDE-4, and the phase 2 KarMMa trial (NCT03361748), according to Munshi. In CARTITUDE-4, patients who received cilta-cel had a median age of 61.5 years (range, 27-78). In KarMMa, patients who received the CAR T-cell therapy idecabtagene vicleucel (Abecma) had a median age of 61 (range, 33-78).

In the future, CAR T-cell therapy may be used earlier in the treatment of patients with multiple myeloma and in older patients with this disease, Munshi concludes.