Treatment Possibilities for R/R Multiple Myeloma After BCMA-Directed CAR T-Cell Therapy

Samir Parekh, MD

Real-world research hints that patients with multiple myeloma who relapse after B-cell maturation antigen chimeric antigen receptor (CAR) T-cell therapy may benefit from multiple lines of salvage therapy, and T-cell engaging therapies.¹

“The findings of this study will serve as a benchmark for future prospective clinical studies that intend to improve the outcomes of patients who progress after CAR-T,” said a senior author on the study,” said Samir Parekh, MD, professor of Medicine, Hematology and Medical Oncology and the director of Translational Research in Multiple Myeloma and co-leader of the Cancer Clinical Investigation program at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, in a press release. “This is the first study to report outcomes of different therapeutic options given to a large cohort of patients who relapsed after anti-BCMA CAR-T therapy. This is one of the most urgent and unmet needs in myeloma patients and, therefore, of great interest to the hematology community,” Parekh added.

BCMA-directed CAR T cells have shown impressive efficacy in patients with relapsed/refractory multiple myeloma.² The activity of this class of agents led to the approval of idecabtagene vicleucel (ide-cel; Abecma) in 2021 for the treatment of adult patients with relapsed or refractory multiple myeloma after 4 or more prior therapies, including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and an anti-CD38 antibody. In the pivotal phase 2 KarMMa trial (NCT03361748), which led to the approval, ide-cel achieved a objective response rate (ORR) of 72% (95% CI, 62%-81%) with complete responses (CRs) in 28% (95% CI, 19%-38%) of patients.

A year later, ciltacabtagene autoleucel (cilta-cel; Carvykti) was approved for the same indication, based on positive results from phase 1/2 CARITUDE clinical trial (NCT03548207). Cilta-cel achieved an ORR of 98% (95% CI, 92.7%-99.7%) with stringent CRs in 78% (95% CI, 68.8%-86.1%) of patients.

Despite the activity observed with BCMA-directed CAR T cells, patients with multiple myeloma still relapse. There is limited knowledge about the prognosis of patient with multiple myeloma in this setting and what therapies can improve their outcomes. To provide more information, experts at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai and Memorial Sloan Kettering Cancer Center retrospectively gathered information about salvage treatments and outcomes of 79 patients with multiple myeloma who had progression of disease after treatment with BCMA-directed CAR T-cell therapy from both centers.²

In the 79 patient records, 237 post-CAR T salvage treatment lines were administered to patients. Overall, the patients received a median of 2 (range, 1-10) treatment lines. Results from this cohort showed a median overall survival of 17.9 months (95% CI, 14.0-not estimable). After relapse, patients were given salvage therapy or T-cell engager therapy. The ORR among those treated with the first salvage regimen was 43.4%. These patients also had a median progression-free survival of 3.5 months (95% CI, 2.5-4.6). Among patients treated with T-cell engagers, the median OS was not reached after a median follow-up of 21.3 months.

Based on this real-world research, T cell-engaging therapies may be able to maintain pronounced clinical activity in patients with relapsed/refractory multiple myeloma.² The retrospective analysis also showed stem cell transplants and combination regimens may be efficacious in these patients.¹

“We’re encouraged that subsequent use of other novel immune therapies like a second CAR-T cell therapy, or a bispecific antibody was feasible and led to durable responses in patients,” said Sham Mailankody, MBBS, associate attending physician, Memorial Sloan Kettering Cancer Center, in the press release. “We look forward to continuing this work and unlocking the full potential of immune therapies for patients with multiple myeloma.”

_REFERENCES:

_{1. Researchers find treatment options for patients whose blood cancer relapses after CAR-T. News release. Mount Sinai Health System. November 4, 2022. Accessed November 7, 2022. https://bit.ly/3ta8MPS}

_{2. Oekelen OV, Nath K, Mouhieddine TH, et al. Interventions and outcomes of multiple myeloma patients receiving salvage treatment after BCMA-directed CAR T therapy. Blood. Published November 3, 2022. doi: 10.1182/blood.2022017848}