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

Autor:	Nishihori T; Moffitt Cancer Center, Tampa, FL., Hoffman JE; Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL., Huff A; GlaxoSmithKline, Collegeville, PA., Kapoor GS; GlaxoSmithKline, Collegeville, PA., Eleftheriadou I; GlaxoSmithKline, Collegeville, PA., Zajic S; GlaxoSmithKline, Collegeville, PA., Urbano A; GlaxoSmithKline, Collegeville, PA., Suchindran S; GlaxoSmithKline, Collegeville, PA., Chisamore M; Merck & Co, Inc, Rahway, NJ., D'Souza JW; GlaxoSmithKline, Collegeville, PA., Faitg T; GlaxoSmithKline, Collegeville, PA., Rapoport AP; University of Maryland Greenebaum Comprehensive Cancer Center and School of Medicine, Baltimore, MD.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2023 Apr 11; Vol. 7 (7), pp. 1168-1177.
DOI:	10.1182/bloodadvances.2022008460
Abstrakt:	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. (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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