CAR-T effective after early relapse for high-risk multiple myeloma
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NEW ORLEANS — Idecabtagene vicleucel induced initial complete remission in nearly half of patients with multiple myeloma who had early relapse after front-line therapy, results of a cohort analysis of the phase 2 KarMMa-2 trial showed.
Investigators noted a median duration of response of nearly 2 years among patients who had an initial complete response to idecabtagene vicleucel (Abecma; Bristol Myers Squibb, 2seventy bio) — also known as ide-cel — according to data presented at ASH Annual Meeting and Exposition.
“The expected survival for these patients is quite poor, with an approximate overall survival of 26 months,” Saad Z. Usmani, MD, MBA, FACP, hematologist-oncologist and chief of myeloma service at Memorial Sloan Kettering Cancer Center. “The fact that 85% of these patients are still alive at 2 years after receiving ide-cel is a very good thing.”
Background & methodology
Ide-cel is an autologous, gene-edited B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy. The FDA approved the agent in March 2021 for adults with relapsed or refractory multiple myeloma who received at least four previous lines of therapy, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 monoclonal antibody.
The multicenter, multiarm KarMMa-2 study evaluated the efficacy and safety of ide-cel as earlier therapy in patients with relapsed or refractory and high-risk multiple myeloma.
Usmani and colleagues presented data at ASH on cohort 2a of the study, which includes patients who had disease progression within 18 months of front-line treatment with hematopoietic stem cell transplant followed by a lenalidomide-containing maintenance therapy.
Cohort 2a enrolled 39 patients, 37 of whom received an infusion of ide-cel and comprise the safety and efficacy analysis population (mean age, 57 years, range 36-77; 56.8% male; 78.4% white; 10.8% Black).
Study participants underwent preconditioning lymphodepletion followed by a single infusion of ide-cel at a median dose of 450 × 106 CAR T cells.
Complete response rate as determined by International Myeloma Working Group criteria served as the study’s primary endpoint. Secondary endpoints included overall response rate, duration of response (DOR), PFS, OS and minimal residual disease (MRD) negativity using next-generation sequencing.
Median follow-up was 21.5 months (range, 2-31), with a data cutoff date of March 14.
Key findings
The study met its primary endpoint, with 45.9% (95% CI, 29.5-63.1) of participants achieving a complete response to therapy.
Investigators reported an ORR of 83.8% (95% CI, 68-93.8), with a median time to response of 1 month (range, 0.9-2.9 months).
Patients who responded to therapy had a median DOR of 15.7 months. Meanwhile, those with an initial complete response to therapy had a median DOR of greater than 23.5 months (95% CI, 10.2 to not estimable).
Results also showed median PFS of 11.4 months (95% CI, 5.6-19.6).
Median OS had not yet been reached, and investigators reported an OS rate of 84.7% at 24 months after ide-cel infusion.
Researchers reported MRD-negativity rates of 68% at 6 months after infusion and 53% at 12 months for all patients in cohort 2a. Those who had an initial complete response to therapy had a MRD negativity rate of 85% at 6 months and 70% at 12 months.
Hematologic adverse events occurred frequently, including neutropenia (94.6%), anemia (56.8%) and thrombocytopenia (51.4%).
Twenty-two patients developed infections (59.5%), with eight cases of grade 3 or grade 4 infection and two infection-related deaths (5.4%).
Cytokine release syndrome occurred in 83.8% of patients but only one patient reported grade 3 or grade 4 symptoms.
Clinical implications
The response rates with ide-cel are impressive given that nearly a quarter of patients in the cohort did not have a complete response to initial front-line therapy, Usmani noted.
Approval of ide-cel as an earlier therapy for multiple myeloma will require positive results from the ongoing randomized phase 3 KarMMa-3 trial comparing the CAR-T against standard-of-care regimens in patients with relapsed or refractory disease, Usmani said.
As previously reported by Healio, topline data published by the manufacturer earlier this year showed ide-cel significantly extended PFS compared with standard regimens for adults with advanced multiple myeloma.
“On paper, there are many good options for patients who have an early relapse, but if ide-cel is given additional regulatory approval, then it would allow us to give these patients a one-time treatment that would not require any additional maintenance therapy,” he told Healio. “This is one of the major advantages of CAR T-cell therapies."
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Usmani S, et al. Abstract 361. Presented at: ASH Annual Meeting and Exposition; Dec. 10-13, 2022; New Orleans.
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