Idecabtagene vicleucel manufacturing and clinical value of out of specification products in relapsed and refractory MM

Idecabtagene vicleucel (ide-cel) is a chimeric antigen receptor (CAR) T cell therapy approved for relapsed and refractory multiple myeloma (RRMM). Out-of-specification (OOS) CAR T cells not meeting criteria for commercial release are considered an investigational product; the expanded access protocol (EAP) allows release of OOS product for administration. The manufacturing analysis of capability, reliability, and timely delivery of ide-cel in the USA over > 3 years since its approval included patients with RRMM who underwent leukapheresis for ide-cel treatment after ≥ 2 prior lines of therapy between February 23, 2021 and November 1, 2024. Additionally, the BB2121-EAP-001 study (NCT04771078) evaluated safety and efficacy of OOS ide-cel and included patients who had undergone leukapheresis for commercial ide-cel treatment not meeting commercial release specifications, most commonly due to high CD137 activation or low infused dose. Primary endpoint was safety. Secondary endpoints were overall response rate (ORR) and complete response rate (CRR). At data cutoff (November 1, 2024), the manufacturing success rate of ide-cel improved from 95.3% in 2021 to 96.8% in 2024. Turnaround time also improved from 31 days in 2021 to 24 days in 2024. In BB2121-EAP-001, 68 (72.3%) patients experienced ≥ 1 cytokine release syndrome event (mostly grade 1/2) and 15 (16.0%) had neurological toxicities (2 grade 3, 13 grade 1/2). ORR was 75.4% (95% CI, 63.1-85.2) and CRR was 35.4% (95% CI, 23.9-48.2). The manufacturing success of ide-cel is reliable and consistently high, and when OOS ide-cel products emerged, they demonstrated consistent clinical efficacy and safety.