Treatment outcomes with unselected autologous tumor infiltrating lymphocytes (TILs) in patients (pts) with checkpoint inhibitionerefractory advanced cutaneous melanoma

Abstract

Background TIL products made from tumor digests showed a high overall response rate (ORR; 67%) and complete response (CR) rate (19%) and a safety profile consistent with lymphodepletion and high-dose interleukin (IL)-2 in a retrospective analysis of a single-center experience of TILs for compassionate use treatment of advanced cutaneous melanoma (n=21; Hawkins, et al. AACR 2021. ePoster LB150). This subanalysis assesses outcomes for pts who received TILs after prior checkpoint inhibition, a pt subset with limited treatment options. Methods Pts with metastatic cutaneous melanoma and no standard of care treatment options received lymphodepleting chemotherapy (cyclophosphamide �2 d; fludarabine �5 d) followed by TIL infusion and post-TIL high-dose IL-2. Safety was assessed by clinically significant adverse events (AEs). Efficacy assessments included ORR, CR rate, and overall survival (OS). Results Of 21 pts who underwent treatment between Oct 2011 and Aug 2019, 12 received prior PD-1 inhibitor (PD-1i) therapy and are reported herein. Median age was 55 y and 50% of pts were BRAF-mutated. Median no. of disease sites was 4, and 100% of pts had M1c or M1d disease (25% with M1d). All pts received prior CTLA-4i and all BRAF-mutated pts received prior BRAFi alone � MEKi. The most commonly reported AEs post-TIL infusion were thrombocytopenia (75%), pyrexia (50%), and rigors (50%). No treatment-related deaths occurred. With a median follow-up of 45.5 mo, the ORR was 58% and the CR rate was 8%. At data cutoff, 2 pts (17%) had durable ongoing responses (>30 mo post-TIL infusion). Median OS in this subanalysis and in the overall population was 21.3 mo. Conclusions In this subanalysis of pts with relapsed advanced melanoma after both PD-1i and CTLA-4i, and for some, BRAFi, outcomes of unselected autologous TILs were similar to those observed in all treated pts, with high response rates and a safety profile consistent with that of TIL therapy. Unselected TILs may address the unmet medical need for the poor-risk subset of pts with advanced melanoma who experience disease progression following checkpoint inhibition and, if applicable, targeted therapy.