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CAR T With Shorter Manufacturing Time Shows High Rate of Deep Response in R/R MM

December 5, 2022

Mid-January 2023

BMS-986354, a B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T-cell therapy with a shortened manufacturing time, showed a high rate of deep response and manageable toxicities in relapsed or refractory multiple myeloma (R/R MM). Results from the phase I study were presented at the 64th ASH Annual Meeting and Exposition.1

Although there have been significant advancements in BCMA-targeting therapies, there is still room for improvement, said presenting author Luciano J. Costa, MD, PhD, of the University of Alabama at Birmingham.

“We have to have a more dependable, fast manufacturing process for CAR T-cell therapy because many patients will perish between [the] collection of cells and completion of manufacturing or receipt of treatment,” Dr. Costa said. “The toxicities associated with CAR T-cell therapy also need to be improved upon.”

BMS-986354 is a next-generation CAR T-cell product that contains the same fully human BCMA-targeted CAR construct as the now-withdrawn orvacabtagene autoleucel (orva-cel).2 However, BMS-986354 is manufactured using the NEX-T process, which was designed to shorten manufacturing time and improve the potency and phenotypic attributes of the CAR T-cell product.

This phase I study consisted of a dose-escalation phase with patients treated at 20 × 106 (dose level [DL] 1, n = 7), 40 × 106 (DL2, n = 24), or 80 × 106 (DL3, n = 11) CAR T cells, and a dose-expansion phase with 13 additional patients treated at DL2.

Dr. Costa noted patients were heavily pretreated with a median of five prior regimens. More than 90% of patients were triple-class refractory.

With a median follow-up of 7.2 months, the objective response rate was 95.1%, with 62.3% achieving very good partial response or better and 39.3% achieving complete response or better.

There was one case of grade 3 or worse cytokine release syndrome (CRS), and the majority of CRS was grade 1 or grade 2 (80.0%). Additionally, there was one case of grade 3 or worse neurotoxicity.

“We saw the expected transient neutropenia, anemia, and thrombocytopenia seen with similar agents,” Dr. Costa said.

The researchers also analyzed the expansion of the cells in vivo and the profile of the cells.

“When we compared the data with the prior orva-cel program, we saw very similar pharmacokinetics despite the fact that we were infusing about 10 times fewer cells,” Dr. Costa said. “The profile of the cells showed more central memory cells than we saw with orva-cel. The hope is that this profile will allow for longer, more durable disease control.”

As for next steps, Dr. Costa said that it is in the hands of the drug manufacturer.

Any conflicts of interest declared by the authors can be found in the original abstract.

Reference

  1. Megala Costa LJ, Kumar SK, Atrash S, et al. Results from the first phase 1 clinical study of the B-Cell maturation antigen (BCMA) Nex T chimeric antigen receptor (CAR) T cell therapy CC-98633/BMS-986354 in patients (pts) with relapsed/refractory multiple myeloma (RRMM). Abstract #566. Presented at the 2022 American Society of Hematology Annual Meeting and Exposition; December 11, 2022; New Orleans, Louisiana.
  2. Terry M. Bristol Myers Takes $470 Million Write-off and Scraps Orva-Cel CAR-T Program. February 11, 2021. Accessed December 1, 2022. https://www.biospace.com/article/bristol-myers-squibb-abandon-s-orva-cel-program/.

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