Publicaciones científicas

Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma

12-may-2021 | Revista: Journal of Clinical Oncology

Amod A Sarnaik  1 , Omid Hamid  2 , Nikhil I Khushalani  1 , Karl D Lewis  3 , Theresa Medina  3 , Harriet M Kluger  4 , Sajeve S Thomas  5 , Evidio Domingo-Musibay  6 , Anna C Pavlick  7 , Eric D Whitman  8 , Salvador Martin-Algarra  9 , Pippa Corrie  10 , Brendan D Curti  11 , Judit Oláh  12 , Jose Lutzky  13 , Jeffrey S Weber  7 , James M G Larkin  14 , Wen Shi  15 , Toshimi Takamura  15 , Madan Jagasia  15 , Harry Qin  15 , Xiao Wu  15 , Cecile Chartier  15 , Friedrich Graf Finckenstein  15 , Maria Fardis  15 , John M Kirkwood  16 , Jason A Chesney  17

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.

CITA DEL ARTÍCULO  J Clin Oncol. 2021 May 12;JCO2100612.  doi: 10.1200/JCO.21.00612