Myeloma Patients Who Relapse After CAR T-Cell Therapy Have Options

Patients with multiple myeloma who relapse after treatment with B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy can be salvaged with multiple lines of therapy, a retrospective study suggested.

Among 79 patients who were given a total of 237 salvage treatments, median overall survival (OS) from the date of relapse post-CAR T-cell therapy was 17.9 months (95% CI 14.0 to not estimable [NE]), reported Samir Parekh, MD, of the Icahn School of Medicine at Mount Sinai in New York City, and colleagues.

Of note, patients who received a T-cell-engaging therapy (a bispecific antibody or subsequent CAR T-cell therapy) had the greatest success in this setting, with OS not reached after a median follow-up of 21.3 months, they noted in Blood.

“Patients with multiple myeloma who relapse after BCMA-directed CAR T have a limited prognosis but can be potentially treated with multiple lines of salvage therapy,” they wrote. “The findings of this study can serve as a benchmark for future prospective clinical studies that intend to improve the outcomes of patients who progress after CAR T.”

The median progression-free survival (PFS) with the first attempted salvage therapy was 3.5 months. The objective response rate (ORR) among these patients was 43.4%, with 9.2% of patients achieving a stringent complete response, 11.8% achieving a very good partial response, and 22.4% achieving a partial response.

Achieving a partial response or better with the first line of salvage therapy was associated with a significantly longer median OS of 29.9 months compared with 14.6 months for patients who did not achieve an objective response (P=0.028).

Of the 44.3% of patients who received a T-cell-engaging therapy at any point after relapse, the ORR was 91.4%. The 13 patients who received a T-cell-engaging therapy immediately after relapse on CAR T had an ORR of 75.0% and a median PFS of 9.1 months.

“This suggests that for eligible patients that progress after BCMA-directed CAR T, additional T-cell-engaging therapies contribute meaningfully to survival and that T-cell activation is feasible down the line,” Parekh and team wrote.

They also noted that transplant-based approaches were effective in the post-CAR T-cell therapy setting. The 20 patients who underwent either autologous or allogeneic stem cell transplant after progression had an OS of 23.2 months (95% CI 17.6 to NE).

However, they suggested that prospective clinical trials are needed to evaluate the role of salvage transplant-based approaches.

In explaining the rationale for the study, Parekh and colleagues noted that while the use of BCMA-directed CAR T-cell therapies in relapsed and refractory multiple myeloma have demonstrated high response rates, optimal treatment regimens have yet to be defined for patients who relapse.

From March 2017 to January 2022, 140 patients with multiple myeloma were treated with a BCMA-directed CAR T-cell therapy on a clinical trial at either the Mount Sinai Tisch Cancer Institute or Memorial Sloan Kettering Cancer Center in New York City. The 79 patients included in this analysis had a median age of 60 years at the time of progression after CAR T-cell therapy, and 60% were men.

They had received a median of five previous treatment lines (including autologous stem cell transplant in 94.9% of patients), and most (83.5%) were triple class-refractory (refractory to ≥1 immunomodulatory drug, ≥1 proteasome inhibitor, and ≥1 anti-CD38 monoclonal antibody).

Patients received a median of two salvage treatments.

Parekh and team acknowledged several limitations to their study, including its retrospective nature. In addition, they noted that at the time of the analysis, 100 of the 140 patients treated with BCMA-directed CAR T at the two centers had relapsed.

“It is therefore possible that our dataset is biased towards those patients with earlier relapse, which might represent a cohort with intrinsically more challenging biological characteristics,” they wrote.

They also pointed out that all of the patients in the study had enrolled in clinical trials, and that “potential trial selection criteria may have introduced a deviation between enrolled patients and the real-world population.”