CT053, Anti-BCMA CAR T-Cell Therapy, for Relapsed or Refractory MM: Proof of Concept

CT053 is a B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell product. These autologous T-cells are genetically modified with a second-generation CAR that incorporates a fully human anti-BCMA single-chain fragment variant, a 41BB co-stimulatory domain, and a CD3-zeta signaling domain.

CT053 was studied in a single-arm, open-label, 3-site, phase 1 study. This study enrolled patients with relapsed or refractory multiple myeloma (RRMM) who received ≥2 prior lines of therapy. Patients were between 18 and 79 years of age. They received a single CT053 infusion after fludarabine and cyclophosphamide treatment.

The primary objective of the study was safety. Adverse events were graded per CTCAE 4.0. Tumor response was assessed per International Myeloma Working Group 2016.

A total of 24 consecutive patients (median age, 62 years; median, 4.5 prior lines of therapy; 11 of 24 with extramedullary disease; 8 of 24 with ECOG 2 or 3) were given a dose of 1.5 × 10⁸ CT053 cells, with the exception of 3 patients who received 0.5 × 10⁸, 1 × 10⁸, and 1.8 × 10⁸ cells, respectively.

After data cutoff (February 2019), hematologic toxic effects were the most common grade 3 or higher adverse events. These included white blood cell count decreased (96%), neutrophil count decreased (88%), lymphocyte count decreased (79%), and thrombocytopenia (67%). One patient died of bone marrow failure and neutropenic infection.

A total of 15 (63%) patients had cytokine release syndrome, all grade 1 or 2. Three (13%) patients had neurotoxicity (two grade 1, one reversible grade 3).

The objective response rate was 88% (21 of 24), including 17 (71%) patients with complete response. Sixteen patients were still in complete response or very good partial response after a median follow-up of 295 days.

Higher CAR T-cell expansion was associated with better responses, and the longest CAR T- cells persisted more than 1 year after the infusion. Extramedullary disease was associated with relapse.

This phase 1 study demonstrated that CT053 is effective with an acceptable safety profile in patients with RRMM.

Abstract OAB-082: Hao S, Jin J, Yu K, et al. CT053, Anti-BCMA CAR T-Cell Therapy for Relapsed/Refractory Multiple Myeloma: Proof of Concept Results from a Phase I Study