Sustained MRD negativity after CAR-T improves outcomes in multiple myeloma
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Key takeaways:
- Those who sustained MRD negativity for more than 6 months achieved longer response duration and PFS.
- All participants with MRD negativity lasting more than 6 months achieved stringent complete response.
Patients with multiple myeloma who exhibited sustained minimal residual disease negativity after treatment with ciltacabtagene autoleucel achieved longer PFS and duration of response, according to study results.
All patients with sustained minimal residual disease (MRD) negativity lasting 6 months or longer achieved stringent complete response after infusion with the chimeric antigen receptor T-cell therapy, a subgroup analysis from the CARTITUDE-1 trial presented at Society of Hematologic Oncology Annual Meeting showed.
“Patients treated on this study with a single dose of [ciltacabtagene autoleucel] and no maintenance therapy were able to achieve a deep and durable responses,” Yi Lin, MD, PhD, assistant professor of oncology at Mayo Clinic in Rochester, Minnesota, said during a presentation.
Background
Ciltacabtagene autoleucel (Carvykti; Janssen, Legend Biotech) — often called cilta-cel — is a B-cell maturation antigen-directed CAR T-cell therapy.
The FDA approved the agent last year for treatment of patients with relapsed or refractory multiple myeloma who received four or more previous lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.
The agency based approval on results from the phase 1b/phase 2 CARTITUDE-1 trial, a single-arm study that included adults with relapsed or refractory multiple myeloma who received at least three previous lines of therapy.
“This particular analysis looks at further details of patients who were able to achieve bone marrow MRD-negative status, including their outcomes and clinical characteristics,” Lin said.
Methodology
Lin and colleagues conducted a retrospective cohort analysis comprising patients from CARTITUDE-1 who achieved MRD negativity after treatment.
Study participants underwent preconditioning lymphodepletion followed by a single dose of cilta-cel at a target dose of 0.75 × 106 cells/kg.
MRD negativity status served as one of the key secondary endpoints for the phase 2 portion of the study. Investigators determined MRD status using next-generation sequencing of bone marrow samples according to International Myeloma Working Group criteria.
The analysis defined sustained MRD negativity as study participants who had two MRD-negative sequencing results — after cilta-cel infusion and prior to disease progression or subsequent therapy — at least 6 months apart, with no MRD-positive results in between.
Key findings
Fifty-six of 61 patients (91.8%) evaluable for MRD achieved MRD negativity status after a single infusion of cilta-cel.
Twenty-two study participants maintained MRD negativity for 6 months or less, 10 maintained it for 6 months to 12 months, and 24 patients maintained it for at least 12 months.
All participants with MRD-negative status lasting at least 6 months achieved stringent complete response to cilta-cel, compared with 55% of patients who had an MRD-negative response lasting less than 6 months.
Researchers reported a 10.3 month (95% CI, 5.1-15.6) median duration of response and 11 month (95% CI, 5.4-16.6) median PFS among patients who had MRD-negative status lasting less than 6 months.
Median duration of response and median PFS had not been reached among patients who sustained MRD-negative status for 6 months or longer.
Clinical implications
"Patients who were able to achieve sustained MRD negativity for 6 months or longer had the best responses," Lin said. "We were unable to find any definitive baseline characteristics that would help predict patients more likely to have sustained bone marrow MRD negativity, although there appears to be a trend toward patients who are further out from their initial diagnosis of multiple myeloma.”
Collapse
Munshi NC, et al. Abstract MM-304. Presented at: Society of Hematologic Oncology Annual Meeting; Sept. 6-9, 2023; Houston.
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