CAR T-Cell Therapy Can Work as Salvage Treatment in Relapsed MM Following BCMA-Directed CAR T

People with multiple myeloma (MM) who relapse following treatment with B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell therapy (CAR T) can be treated with multiple lines of salvage therapy, including further CAR T treatments, according to a new report.

The study, published in Blood, offers rare insights into the experiences of patients who relapse following BCMA-directed CAR T, in which a patient’s own T cells are essentially reprogrammed to identify and eliminate cells that express BCMA.

The study authors said there are currently 2 BCMA-directed CAR T therapies available for people with relapsed or refractory MM (RRMM) who are triple-class exposed following at least 4 prior lines of therapy. The therapies have high response rates, but they said a significant number of patients will relapse following therapy. In such cases, there is little existing evidence to guide physician and patient decision-making.

“With the recent approval of 2 different BCMA-directed CAR T-cell therapies and the increasing use of these treatments in patients with RRMM, understanding the natural course of patients with post–CAR T progression will enable a better navigation of treatment options for these patients,” the authors said.

In the new report, they looked at what happened to 79 patients from 2 academic medical institutions who were treated with BCMA-directed CAR T therapy and later experienced disease progression. The patients had a median age of 60 at progression, and most (59.5%) were male.

Those patients ended up undergoing 237 salvage treatment lines following their CAR T treatment (median of 2 lines). They survived for a median of 17.9 months following their post–CAR T relapse (95% CI, 14.0-not estimable). The most common types of salvage therapy were doublet, triplet, or quadruplet combinations of approved agents and chemotherapy with or without stem cell support.

Overall, 43.4% of patients responded to their first salvage regimen, and they had a median progression-free survival (PFS) of 3.5 months (95% CI, 2.5-4.6).

“In the absence of a standard-of-care approach for relapse post BCMA-directed CAR T, a wide range of management strategies were utilized as the subsequent antimyeloma regimen,” the authors said.

However, the study also showed that CAR T could work as a salvage treatment. Thirty-five patients received either a bispecific antibody or additional round of CAR T as salvage treatment, and those patients had a median PFS exceeding 9 months, the investigators said. The overall survival of that group was not reached after a median follow-up of 21.3 months, they added.

“This suggests that for eligible patients who 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,” the authors wrote.

That said, they cautioned that the patients in this data set who received CAR T-cell therapies did so on clinical trials, and thus they had to meet eligibility criteria and go through washout periods.

“Therefore, it is conceivable that these patients may have a different disease biology and prognosis compared with patients who may not meet the eligibility requirements of such trials,” they wrote.

The authors said this study is an important first step in deciphering a path forward for people who relapse following BCMA-directed CAR T. In addition to further trials of such patients, they said additional research into the causes of CAR T failure may also help direct future treatment decisions.

Reference

Van Oekelen O, Nath K, Mouhieddine TH, et al. Interventions and outcomes of multiple myeloma patients receiving salvage treatment after BCMA-directed CAR T therapy. Blood. Published online November 3, 2022. doi:10.1182/blood.2022017848