An investigational chimeric antigen receptor (CAR) T-cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA) showed clinical activity in heavily pretreated patients with relapsed/refractory multiple myeloma, according to the results of a single-arm, multicenter, phase 1 trial (ClinicalTrials.gov Identifier: NCT03274219).

The trial results were presented at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.

The CAR-T therapy, known as bb21217, uses the same CAR molecule as idecabtagene vicleucel but differs in that it is cultured ex vivo with the PI3K inhibitor bb007. This additional step enriches the product for memory-like T cells before infusion. 


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A total of 69 patients were infused with bb21217, and among the 3 doses evaluated, the highest dose — 450 million CAR T cells — was selected as the recommended phase 2 dose.

Most patients received the highest dose, and the study population was heavily pretreated, having received between 3 and 17 prior lines of therapy (median, 6 prior lines of therapy).

Grade 3 or 4 hematological events were common and included lymphopenia, leukopenia, anemia, thrombocytopenia, and neutropenia.

Among 69 patients treated, 48 (70%) developed cytokine release syndrome (CRS), which was mostly grade 1 or 2. Two patients died from CRS. Neurotoxicity was seen in 11 patients (16%), which included 2 patients with grade 3 toxicity and 1 with grade 4 toxicity.

The overall response rate was 68%, which included 29% of patients who achieved a complete response or better and 25% who achieved a very good partial response. Most patients who achieved a partial response were also negative for minimal residual disease (MRD), and all patients who experienced complete responses were MRD-negative.

Responses lasted for a median of 17 months.

While the trial was enrolling patients on the recommended phase 2 dose, the manufacturing process changed, explained the study presenter Melissa Alsina, MD, of the department of blood and marrow transplant and cellular immunotherapy at H. Lee Moffitt Cancer Center Hematologic Malignancies Program in Tampa, Florida.

For the 29 patients who received the recommended phase 2 dose after the manufacturing change, the response rate was 84%, which was higher than the 60% response rate seen in patients who received the same dose before the change.

Dr Alsina said this response rate is “encouraging,” but cautioned that the follow-up is short. “We have to wait a little bit more to see if this is sustained.”

Disclosures: Some of the presenters disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the presentation abstract.

Reference

Alsina M, Shah N, Raje NS, et al. Updated results from the phase I CRB-402 study of anti-Bcma CAR-T cell therapy bb21217 in patients with relapsed and refractory multiple myeloma: Correlation of expansion and duration of response with T cell phenotypes. Presented at: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract 130.

This article originally appeared on Cancer Therapy Advisor