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Lifileucel, a tumor-infiltrating lymphocyte therapy, in metastatic melanoma

Autores: Sarnaik, A. A. (Autor de correspondencia); Hamid, O.; Khushalani, N. I.; Lewis, K. D.; Medina, T.; Kluger, H. M.; Thomas, S. S.; Domingo-Musibay, E.; Pavlick, A. C.; Whitman, E. D.; Martín Algarra, Salvador; Corrie, P.; Curti, B. D.; Olah, J.; Lutzky, J.; Weber, J. S.; Larkin, J. M. G.; Shi, W.; Takamura, T.; Jagasia, M.; Qin, H.; Wu, X.; Chartier, C.; Finckenstein, F. G.; Fardis, M.; Kirkwood, J. M.; Chesney, J. A.
ISSN: 0732-183X
Volumen: 39
Número: 24
Páginas: 2656 - 2666
Fecha de publicación: 2021
PURPOSE Effective treatment options are limited for patients with advanced (metastatic or unresectable) melanoma who progress after immune checkpoint inhibitors and targeted therapies. Adoptive cell therapy using tumor-infiltrating lymphocytes has demonstrated efficacy in advanced melanoma. Lifileucel is an autologous, centrally manufactured tumor-infiltrating lymphocyte product. METHODS We conducted a phase II open-label, single-arm, multicenter study in patients with advanced melanoma who had been previously treated with checkpoint inhibitor(s) and BRAF +/- MEK targeted agents. Lifileucel was produced from harvested tumor specimens in central Good Manufacturing Practice facilities using a streamlined 22-day process. Patients received a nonmyeloablative lymphodepletion regimen, a single infusion of lifileucel, and up to six doses of high-dose interleukin-2. The primary end point was investigator-assessed objective response rate (ORR) per RECIST, version 1.1. RESULTS Sixty-six patients received a mean of 3.3 prior therapies (anti-programmed death 1 [PD-1] or programmed death ligand 1 [PD-L1]: 100%; anticytotoxic T-lymphocyte-associated protein-4: 80%; BRAF +/- MEK inhibitor: 23%). The ORR was 36% (95% CI, 25 to 49), with two complete responses and 22 partial responses. Disease control rate was 80% (95% CI, 69 to 89). Median duration of response was not reached after 18.7-month median study follow-up (range, 0.2-34.1 months). In the primary refractory to anti-PD-1 or PD-L1 therapy subset, the ORR and disease control rate were 41% (95% CI, 26 to 57) and 81% (95% CI, 66 to 91), respectively. Safety profile was consistent with known adverse events associated with nonmyeloablative lymphodepletion and interleukin-2. CONCLUSION Lifileucel demonstrated durable responses and addresses a major unmet need in patients with metastatic melanoma with limited treatment options after approved therapy, including the primary refractory to anti-PD-1 or PD-L1 therapy subset.