Ide-cel CAR-T significantly extends PFS in advanced multiple myeloma
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Idecabtagene vicleucel significantly extended PFS compared with standard regimens for adults with triple-class refractory multiple myeloma, results of the randomized phase 3 KarMMa-3 trial showed.
A single-infusion of the modified cellular therapy also induced a significantly higher response rate than standard regimens, according to data presented at European Society for Blood and Marrow Transplantation-European Hematology Association (EHA) 5th European CAR T-cell Meeting and published in The New England Journal of Medicine.
The findings correspond to a 51% reduction in risk for disease progression or death among those who received idecabtagene vicleucel (Abecma; Bristol Myers Squibb, 2seventy bio) as earlier therapy compared with standard treatment regimens.
“These results support the use of ide-cel [for] patients with early-line relapse and triple class-exposed relapsed or refractory multiple myeloma, a patient population with poor survival outcomes,” Paula Rodríguez-Otero, MD, PhD, associate professor at University of Navarra in Pamplona, Spain, said during a presentation.
Background
Despite the development of new agents for multiple myeloma, all patients ultimately relapse. Those with triple-class refractory disease experience poor outcomes when provided further therapy.
“In the absence of an established standard of care for triple class-exposed relapsed or refractory multiple myeloma, therapies with novel mechanisms of action that provide deeper and more durable responses are needed in earlier lines of treatment,” Rodríguez-Otero said.
Idecabtagene vicleucel — also known as ide-cel — is a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell therapy. The FDA approved the agent in 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 KarMMa-3 trial evaluated whether ide-cel would confer more durable treatment responses as earlier therapy than standard regimens for relapsed or refractory multiple myeloma.
Methodology
The trial included adults with relapsed or refractory multiple myeloma who received two to four prior lines of treatment.
Two-thirds of patients had triple class-refractory disease, with a 95% refractory to treatment with daratumumab (Darzalex, Janssen).
Researchers randomly assigned 254 patients (median age, 63 years; range, 30-81; 61% men; 68% white) to ide-cel.
The other 132 (median age, 63 years; range, 42-83; 60% men; 59% white) received one of five standard regimens. These included combinations of agents such as daratumumab, pomalidomide (Pomalyst, Bristol Myers Squibb), dexamethasone, bortezomib (Velcade, Millennium/Takeda), ixazomib (Ninlaro, Takeda), lenalidomide (Revlimid, Bristol Myers Squibb), carfilzomib (Kyprolis, Amgen) or elotuzumab (Empliciti, Bristol Myers Squibb).
Study participants underwent optional bridging therapy followed by preconditioning lymphodepletion and a single IV infusion of ide-cel at a target dose of range of 150 × 106 to 450 × 106 CAR T cells.
PFS served as the study’s primary endpoint. Secondary endpoints included overall response rate, OS and safety.
Median follow-up was 18.6 months (range, 0.4-35.4), with a data cutoff date of April 18, 2022.
Key findings
Investigators reported significantly longer median PFS among those who received ide-cel (13.3 months vs. 4.4 months; HR = 0.49; 95% CI, 0.38-0.65).
Results also showed a higher ORR (71% vs. 42%) and complete response rate (39% vs. 5%) in the ide-cel group. OS data had not matured.
The majority of patients in each group experienced grade 3 or grade 4 treatment-related adverse events (93% for ide-cel vs. 75% for standard therapy).
Neutropenia was the most common hematologic adverse event (78% for ide-cel vs. 44% for standard therapy).
The majority (88%) of patients who received ide-cel developed cytokine release syndrome, with 5% of cases being grade 3 or higher. Fifteen percent developed neurotoxicity, with 3% of cases being grade 3 or higher.
Clinical implications
This was the first randomized, phase 3 study to compare a CAR T-cell therapy with standard treatment for patients with triple-class refractory multiple myeloma, according to Rodríguez-Otero.
Results thus far suggest ide-cel provides benefit, she said.
“A single infusion of ide-cel treatment demonstrated significant and clinically meaningful improvement in PFS and [overall response rate] versus standard regimens,” she said.
References:
- Rodríguez-Otero P, et al. Abstract BA02-7. Presented at: European Society for Blood and Marrow Transplantation-European Hematology Association 5th European CAR T-cell Meeting; Feb. 9-11, 2023; Rotterdam, Netherlands.
- Rodríguez-Otero P, et al. New Engl J Med. 2023;doi;10.1056/NEJMoa2213614.
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Rodríguez-Otero P, et al. Abstract BA02-7. Presented at: European Society for Blood and Marrow Transplantation-European Hematology Association 5th European CAR T-cell Meeting; Feb. 9-11, 2023; Rotterdam, Netherlands.
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