Global Manufacturing Experience with Idecabtagene Vicleucel in Patients with Relapsed and Refractory Multiple Myeloma

Introduction Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T cell therapy, is currently approved in the USA, European Union (EU; including Switzerland), and Japan for patients with relapsed and refractory multiple myeloma (RRMM) after ≥ 2 prior lines of therapy based on the phase 3 KarMMa-3 study (NCT03651128; Rodríguez-Otero P, et al. N Engl J Med 2023). In the pivotal KarMMa-3 clinical trial, the manufacturing success rate for ide-cel was 98.8%. Globally, 227 centers are qualified for treating patients with commercially available ide-cel; 111 in the USA, 91 in the EU (including Switzerland), and 25 in Japan. With CAR T cell therapies, including ide-cel, timely and reliable delivery of the product in both commercial and clinical trial settings is essential to optimize treatment outcomes for patients with RRMM (Ailawadhi S, et al. Clin Lymphoma Myeloma Leuk 2023). The manufacturing capability, reliability, and timely delivery of ide-cel over more than 3 years is reported here. Methods This analysis includes patients with RRMM, as captured on the Cell Therapy 360® portal, who underwent leukapheresis for ide-cel treatment after ≥ 2 prior lines of therapy between February 23, 2021, and May 1, 2024, and had final manufacturing outcomes (defined as meeting commercial specifications by qualified person, or not meeting commercial specifications but released based on physician's request, rejected, or terminated) available. The analysis also included clinically manufactured ide-cel utilized in the KarMMa-3 trial. The manufacturing success rate (MSR) was defined as the percentage of patients for whom the product was released that either met commercial specifications, or through the expanded access protocol, single investigational new drug, or through the exceptional supply of advanced therapy medicinal products (EU-Good Manufacturing Practice, part IV, section 11.5). Manufacturing turnaround time (TAT) for commercial and clinical trial ide-cel was defined as the number of days from leukapheresis to product release. Results Between February 2021 and May 2024 (data cutoff May 1, 2024), 4117 patients underwent leukapheresis for commercial ide-cel and had final manufacturing outcomes available. Between 2021 and 2024, the overall MSR for ide-cel was 96.8%. The MSR improved over 3 years; 95.8% in 2021, 96.4% in 2022, 97.2% in 2023, and 98.0% in 2024 (May 1). In 2024 the commercial MSR was consistent between the USA (97.7%), the EU (98.3%), and Japan (98.0%). The current commercial median (interquartile range [IQR]) TAT demonstrated year-on-year improvements from 2021 through 2024, from 31 (28−35) to 24 (24−25) days in the USA, 48 (46−53) to 33 (32−35) days in the EU, and from 47 (40−48) days in 2022 to 35 (34−36) days in 2024 in Japan. In the KarMMa-3 clinical trial setting, the overall median (IQR) clinical TAT from 2019 through 2022 was 30 (28−35) days in the USA, 39 (34−46) days in the EU (including Switzerland, United Kingdom, and Norway), and 45 (39−60) days in Japan. Conclusions The timely and reliable delivery of CAR T cell products is essential for effective patient planning and optimizing treatment outcomes in RRMM. The commercial manufacturing reliability of ide-cel has been notably high since 2021. This analysis has revealed further consistent year-on-year enhancements in MSR and TAT of ide-cel for patients worldwide over the past 3 years, enabling the manufacturing of ide-cel to meet the increasing global patient demand effectively.