CAR-T equally safe, effective for older patients with advanced multiple myeloma
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Complete responses to idecabtagene vicleucel appeared consistent regardless of age among patients with relapsed or refractory multiple myeloma, according to study results presented at TCT Meetings Digital Experience.
Researchers reported a low incidence of severe treatment-related toxicities among patients aged 65 years or older.
“Elderly patients are often categorized as being frail. Thus, many studies of aggressive interventions often exclude this patient population,” Jesús G. Berdeja, MD, director of multiple myeloma research at Sarah Cannon Research Institute, told Healio. “In the pivotal phase 2 KarMMa study ... the efficacy outcomes in elderly patients were comparable with those observed in the overall ide-cel-treated population, and there were no new safety signals observed.”
Idecabtagene vicleucel (bb2121; bluebird bio, Bristol Myers Squibb), also known as ide-cel, is an investigational autologous chimeric antigen receptor T-cell therapy that targets the B-cell maturation antigen (BCMA) when it is expressed on the surface of cancer cells. The treatment has not been approved for use in the United States but was granted priority review by the FDA in September.
The FDA based its decision on results of the open-label, single-arm, multicenter, phase 2 KarMMa trial, which showed ide-cel induced “deep and durable responses” in patients with heavily pretreated relapsed and refractory multiple myeloma, Berdeja said.
The trial included 128 patients (median age, 61 years; range, 33-78; 59% men) who received ide-cel as of Jan. 14, 2020. For their subset analysis, Berdeja and colleagues examined outcomes of patients aged 65 years or older (n = 45) and 70 years or older (n = 20) compared with the overall study population.
Baseline characteristics appeared comparable among older patients and the overall population, except for the proportion of patients with high tumor burden, which was highest (65%) among patients aged 70 years or older.
Patients received a median six (range, 3-16) previous lines of therapy, including an immunomodulatory agent, a proteasome inhibitor and an antiCD38 antibody. All were refractory to their last line of treatment, according to International Myeloma Working Group criteria, and 84% had triple-refractory disease.
Patients received lymphodepleting chemotherapy with 300 mg/m2 cyclophosphamide and 30 mg/m2 fludarabine daily for 3 days, followed by an infusion of ide-cel at one of three dose levels: 150 × 106 CAR T cells, 300 × 106 CAR T cells or 450 × 106 CAR T cells.
Overall response rate served as the study’s primary endpoint. Secondary endpoints included complete response rate, duration of response, PFS, OS, minimal residual disease status, pharmacokinetics, quality of life and safety.
Results showed older patients had higher response rates than the overall study population. Patients aged 65 years or older had an ORR of 84%, including a 90% ORR among those aged 70 years or older. The ORR for the overall population was 73%.
The complete response rate also was highest among the subset of patients aged 70 years or older (35%) compared with those aged 65 years or older (31%) and the overall population (33%).
Median time to first response was 1 month, with median duration of response ranging from 10.7 months to 11 months across age groups.
Median PFS was 10.2 months (95% CI, 3.1-12.3) among those aged 70 years or older, 8.6 months (95% CI, 4.9-12.2) among those aged 65 years or older and 8.8 months (95% CI, 5.6-11.6) among all patients.
OS data were immature as of the data cutoff point.
All patients aged 70 or older developed cytokine release syndrome (CRS), compared with 84% of the entire study population. Two of seven patients who had grade 3 or higher CRS were aged 70 years or older. Median time to onset of CRS was 1 day and median duration was 5 days.
Twenty-three patients (18%) had some form of neurotoxicity, including 11 patients (24%) aged 65 years or older and six patients (30%) aged 70 years or older. All four patients with grade 3 neurotoxicity were aged 65 years or older.
Time to onset of neurotoxicity was similar among the groups (median, 2 days); however, median duration of neurotoxicity was longer among patients aged 65 years or older (5 days) and 70 years or older (6 days) compared with the overall study population (3 days).
“Similar to what has been reported with the overall KarMMa study, the responses in this elderly, refractory population [with multiple myeloma] compare very favorably to agents approved in this indication,” Berdeja told Healio.
Berdeja said an FDA decision is expected and he anticipates patients will have commercial access to the therapy as soon as this spring.
“Once ide-cel becomes commercially available, age alone should not be used a determinant of eligibility for this therapy,” he added.
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Berdeja J, et al. Abstract 486. Presented at: The 2021 TCT Meetings Digital Experience (virtual meeting); Feb. 8-12, 2021.
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