Patients (pts) with R/R large B-cell lymphoma (LBCL) treated with lisocabtagene maraleucel (liso-cel) nonconforming product (NCP) under the Expanded Access Protocol (EAP).
Authors: Till Brian G. , Jacobson Caron Alyce , Palomba Maria Lia , Abramson Jeremy S. , Arnason Jon , Locke Frederick L , Caimi Paolo Fabrizio , Grover Natalie Sophia , Karmali Reem , Suh Hyung C. , Schuster Stephen J. , Gharibo Mecide Meric , Balint Catherine , Rakhmawati Trias , Jude Veronica , Nastoupil Loretta J. 
Published: June 2024

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Background: Liso-cel is an autologous, CD19-directed, 4-1BB CAR T cell product indicated for the treatment of adults with R/R LBCL. Liso-cel NCP is defined as any product wherein one or both of the CD8 or CD4 cell components did not meet ≥ 1 of the commercial release specifications but met EAP release criteria and was considered appropriate for infusion. Methods: This is a prospective, multicenter EAP study of pts with R/R LBCL intended to receive commercial liso-cel but were treated with NCP due to manufacturing outcomes. Data from United States pts are reported here. The study comprised a pretreatment period for pt evaluation, a treatment period, which started at the first dose of lymphodepleting chemotherapy and continued through NCP administration at Day 1, and the posttreatment period, which followed pts up to 3 months after NCP administration for safety and disease status. Study objectives were safety (primary endpoint) and effectiveness by ORR and CR rate assessed by the treating physician per Lugano 2014 criteria (secondary endpoint). Due to the 3-month follow-up, duration of response, PFS, and OS analyses could not be estimated. Results: A total of 167 United States pts (third-line or later, n = 145; second line, n = 22) were included in the analysis set (data cutoff: 11/20/2023), which included pts who were infused and completed 3 months of follow-up (n = 134) or discontinued participation or died before 3 months (n = 33). Median (IQR) time from leukapheresis to NCP infusion was 50 d (44–58). Median age was 69 y (range, 29–87), 57% male, 42% diffuse LBCL (DLBCL) not otherwise specified, and 29% transformed DLBCL. The most frequent types of NCP (≥ 10 cases) were CD4 low T-cell lineage purity (n = 37 [22%]), CD4 low or high vector copy number (n = 31 [19%]), CD4 low transduction frequency (n = 24 [14%]), or CD8 high interferon-γ (n = 12 [7%]). Bridging therapy was reported in 31% of pts. In the total population (N = 167), cytokine release syndrome was reported in 42% of pts (1% grade ≥ 3), neurological events in 8% (4% grade ≥ 3), immune effector cell–associated neurotoxicity in 2% (1% grade ≥ 3), prolonged cytopenia in 40% (grade ≥ 3 on or after Day 29), grade ≥ 3 infections in 14%, infusion-related reactions in 1% (grade ≥ 3), and second primary malignancy in 1% (none grade ≥ 3). Thirteen pts died because of: AEs (n = 6), disease progression (n = 5), or unknown reasons (n = 2). Of 118 efficacy-evaluable pts for best overall response in the first 3 months, ORR was 71% (95% CI, 62–79); 53% had a CR (95% CI, 43–62) and 19% had a PR (95% CI, 12–27). Conclusions: These data add to current clinical experience with liso-cel, show that pts with R/R LBCL can derive clinical benefit from receiving NCP without compromising safety, and provide important evidence to facilitate clinical decision-making. Clinical trial information: NCT04400591 .