TIL Therapy Induces Responses Across Wide Range of Patients with Previously Treated Advanced Melanoma

September 2020 Vol 11, No 9



A single infusion of autologous cryopreserved tumor-infiltrating lymphocyte (TIL) therapy (lifileucel) induced responses in more than one-third of patients with advanced melanoma who had disease progression on multiple prior therapies, including anti–PD-1 and BRAF/MEK inhibitors, according to an update of a phase 2 global multicohort study.

Data reported at the ASCO20 Virtual Scientific Program showed a reduction in tumor burden in 81% of evaluable patients receiving cryopreserved lifileucel in the open-label trial.

Response data indicate that “lifileucel therapy can result in responses for those who have metastatic melanoma that is primarily refractory to PD-1 antibody therapy,” said lead investigator Amod Sarnaik, MD, surgical (cutaneous) oncologist, Moffitt Cancer Center, Tampa, FL.

There are currently no effective approved agents for patients with advanced metastatic melanoma after disease progression following immune checkpoint inhibition and progression after BRAF/MEK inhibitor therapy for those whose tumors have activating mutations in the BRAF proto-oncogene.

The study population consisted of patients with unresectable or metastatic melanoma who had progressed after treatment with at least 1 systemic therapy, including a PD-1–blocking antibody and, if BRAF V600 mutation positive, a BRAF inhibitor or BRAF/MEK inhibitor. The data presented were from cohort 2 of the study, in which 66 patients received cryopreserved TIL therapy.

The cohort 2 patients were heavily pretreated with high baseline disease burden (106 mm mean sum of diameters of target lesions), having progressed on a mean of 3.3 prior therapies, including 100% who had received prior anti–PD-1 therapy, and 80% who had received prior anti–CTLA-4 therapy. Fifteen of the 17 patients whose tumors had BRAF V600–activating mutations had prior BRAF/MEK inhibitor therapy. Some 77% of patients had >3 target or nontarget lesions at baseline, with a mean of 6 lesions, and 42% had baseline liver and/or brain metastases.

“In general, the adverse events were typically expected for a treatment regimen that includes nonmyeloablative lymphodepleting chemotherapy and infusional bolus interleukin-2,” said Dr Sarnaik. They included grade 3/4 thrombocytopenia in 81.8%, grade 3/4 anemia in 56.1%, and grade 3/4 febrile neutropenia in 54.5%. The peak onset of toxicities tended to occur relatively soon after TIL infusion “with a paucity of new adverse events that start beyond 14 days of TIL infusion,” he added.

The objective response rate (ORR) in cohort 2 was 36.4%, with 2 (3.0%) complete responses and 22 (33.3%) partial responses. An additional 43.9% had stable disease as their best response. Four patients who were not evaluable were included as nonresponders. After a median follow-up of 18.7 months, the median duration of response was still not reached. Responses were seen regardless of the location of the tumor resected.

Durable responses were demonstrated across a wide age range of patients with metastatic melanoma, including those who progressed on prior anti–CTLA-4 and BRAF-targeted treatments, regardless of BRAF mutational status, and equally in patients with PD-L1 high and low status.

There was a trend toward a lower response rate compared with the overall cohort in patients with a baseline lactate dehydrogenase level ≥2 times the upper limit of normal (ORR of 12.5%) and in those with a sum of diameters of target lesions at baseline ≥70 mm (ORR of 25.0%). These trends, however, were not significant. Responses were observed in patients with bulky disease or with liver and/or brain lesions at baseline.

“Overall, these data indicate that responses from lifileucel therapy are achievable for subjects across a relatively broad range of clinical and pathologic features,” said Dr Sarnaik. The responses deepened over time, he said, and 16 responses extended beyond 1 year. Some 79% of responders had received prior ipilimumab.

The adverse event profile was consistent with the underlying advanced disease, lymphodepletion, and interleukin-2 regimens.

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Last modified: August 10, 2023

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