Safety and efficacy of letetresgene autoleucel alone or with pembrolizumab for relapsed/refractory multiple myeloma

• Published in: Blood advances Vol. 7; no. 7; pp. 1168 - 1177
• Main Authors: Nishihori, Taiga, Hoffman, James E., Huff, Anne, Kapoor, Gurpreet S., Eleftheriadou, Ioanna, Zajic, Stefan, Urbano, Alisa, Suchindran, Sunil, Chisamore, Michael, D’Souza, Jimson W., Faitg, Thomas, Rapoport, Aaron P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.04.2023; The American Society of Hematology
• Subjects: Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Humans; Immunobiology and Immunotherapy; Multiple Myeloma - drug therapy; Multiple Myeloma - genetics; Pilot Projects
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2022008460

•Lete-cel was well tolerated and showed antigen-specific antitumor activity in patients with relapsed/refractory multiple myeloma.•Lete-cel is a targeted therapy that showed HLA-restricted and antigen-specific (NY-ESO-1/LAGE-1A) antitumor activity in patients with relapsed/refractory multiple myeloma. [Display omitted] This pilot study assessed the safety and efficacy of letetresgene autoleucel (lete-cel; GSK3377794), a genetically modified autologous T-cell therapy targeting New York esophageal squamous cell carcinoma-1 (NY-ESO-1)/L antigen family member 1 isoform A (LAGE-1a)–positive myeloma cells, alone or in combination with pembrolizumab in patients with relapsed/refractory multiple myeloma. Eligible patients expressed NY-ESO-1 and/or LAGE-1a and either HLA-A∗02:01, ∗02:05, or ∗02:06. Patients received lete-cel single infusion alone (arm 1) or with pembrolizumab (arm 2). 127 patients were screened, and 6 patients (3 per arm) were enrolled; patients in arm 1 and 2 received lete-cel alone, or with pembrolizumab, respectively. All patients exhibited grade 3/4 cytopenias, which resolved or improved to grade 1. One patient (arm 1) had grade 3/4 lete-cel–related adverse events (AEs); 2 patients (arm 2) had grade 3/4 AEs related to lete-cel and lymphodepletion. Three patients with grade 1/2 cytokine release syndrome (CRS) exhibited elevated post–lete-cel interleukin-6 levels versus those without CRS. Pooled overall response rate was 50% including 1 patient each with confirmed clinical response, very good clinical response, and partial response, and progression-free survival ranged from 1.3 to 5.2 months. Responders (arm 1: n = 1; arm 2: n = 2) had a time-to-response of 3 weeks, duration of response of 2.1 months. Two responders, but no nonresponders, exhibited elevated cytokine levels after lete-cel infusion. Lete-cel had a manageable safety profile and demonstrated clear but transient antitumor activity in patients with relapsed/refractory multiple myeloma. This trial was registered at www.clinicaltrials.gov as #NCT03168438.