Cilta-Cel could be a lasting therapy for patients with progressive myeloma

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Although patients with multiple myeloma who have progressed on 1 to 3 previous lines of treatment and who are refractory to lenalidomide (Revlimid) need a more durable treatment option, ciltacabtagene autoleucel (cita-cel) may offer a potential solution, according to Adam D. Cohen, MD.

CAR T-cell therapy was evaluated in the CARTITUDE-2 study, designed to assess its efficacy and safety. The first results from Cohort A of the trial were presented at the 18th International Myeloma Workshop by Coheh, associate professor at the University of Pennsylvania.

“These responses appear to deepen over time and monitoring is ongoing,” he said. “Of course, what we’re all waiting for is longer-term follow-up to see if the sustainability of the response is going to be better in this less heavily treated population compared to the more refractory patients treated historically.”

Cohorts B, C, D and E, for which data are still being analyzed, consist of patients with an early relapse after first-line treatment and who progress after previous treatment targeted on the maturation antigen B cells (BCMA), or in union for patients after transplantation or induction therapy.

The primary objective of the researchers was minimal residual disease negativity (MRD) with a sensitivity of 10-5 assessed by next-generation sequencing, with secondary objectives of overall response rate (ORR), duration of response, time and duration of MRD negativity; and incidence and severity of adverse events (AEs).

A single infusion of cilta-cel was given to 20 patients 5-7 days after the onset of lymphodepletion. With a median follow-up of 5.8 months to the cut-off date, the ORR was 95%, including 75% of patients achieving complete response (CR) or better.

The safety profile was consistent with that seen in previous studies, with the majority of non-hematologic AEs being low grade. The most common grade 3/4 hematologic AEs included neutropenia (90%), thrombocytopenia (35%), anemia (40%), lymphopenia (55%) and leukopenia (55%). Grade 3/4 neutropenia and lymphopenia persisted after 60 days in 25% and 45% of patients, respectively.

Additionally, 85% of patients developed cytokine release syndrome (CRS), the majority being grade 1 or 2 events. Several patients (15%) developed immune effector cell-associated neurotoxicity syndrome (ICANS). typical bound to CAR T cells.

“A number of mitigation strategies have been implemented in the CAR T program since then, including improved bridging therapy to reduce tumor burden prior to infusion, early and aggressive treatment of CRS and ICANS,” as well as handwriting ratings, as microgravity was a presentation feature in some cases. of patients, ”Cohen said.

Implementation of these strategies significantly reduced the incidence of movement disorders and neurocognitive disorders in the more than 100 additional patients who received doses in the time since the data cut-off date. However, the follow-up is still ongoing, Cohen explained.

Cilta-cel continues to be evaluated in a phase 3 study, CARTITUDE-4, in which it is compared to standard therapy.

Reference

Cohen A, Agha M, Madduri D, et al. Efficacy and safety of ciltacabtagene autoleucel, a CAR-T cell therapy directed by BCMA, in patients with progressive multiple myeloma after 1 to 3 previous lines of treatment: first results of CARTITUDE-2. Presented at: 18th International Workshop on Myeloma; from September 8 to 11, 2021; Vienna, Austria.


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