TIL therapy still effective in advanced melanoma despite prior anti-PD-(L)1 treatment

The clinical response or survival benefit derived by patients with advanced cutaneous melanoma from adoptive cell therapy with tumor-infiltrating lymphocytes (TIL-ACT) does not wane even with prior antiprogrammed cell death protein 1/programmed death-ligand 1 (anti-PD-[L]1) treatment, according to a study. TIL therapy also provides benefits in the second-line setting after anti-PD-(L)1 treatment.

“Our data reinforce the evidence that TIL-ACT should be considered as a treatment of choice in second line for metastatic melanoma patients failing anti-PD-(L)1 therapy,” the investigators said.

In this study, PubMed was comprehensively searched until 29 February 2024 for studies including high-dose interleukin 2. The investigators doubled the number of patients from their previous meta-analysis conducted up to December 2018 and used overall survival (OS) as the primary endpoint. Secondary endpoints were objective response rate (ORR), complete response rate (CRR), and duration of response.

Tables, Kaplan‒Meier plots, and forest plots were used to synthesize the findings. Finally, the investigators derived pooled estimates for ORR and CRR from fixed or random effects models.

Thirteen high-dose interleukin 2 studies met the eligibility criteria of the updated meta-analysis, providing OS data for 617 patients. [Ann Oncol 2024;35:860-872]

Median OS did not significantly differ between studies with prior anti-PD-(L)1 treatment (n=238; 17.5 months, 95 percent confidence interval [CI], 13.8‒20.5) and without (n=379; 16.3 months, 95 percent CI, 14.2‒20.6; log-rank p=0.53).

Estimated ORR was 34 percent (95 percent CI, 16‒52) for studies with prior anti-PD-(L)1 treatment and 44 percent for those without. The pooled estimate for CRR was 10 percent for the two groups. Notably, no statistically significant differences were noted between studies with and without prior anti-PD-(L)1 therapy either for ORR (p=0.15) or CRR (p=0.45).

“Our updated meta-analysis study demonstrates that TIL-ACT remains a clearly efficacious strategy in patients failing anti-PD-(L)1 immunotherapy,” the investigators said.

“No significant impact of prior anti-PD-(L)1 treatment on the efficacy of TIL-ACT in patients with advanced cutaneous melanoma was identified, and it was confirmed that patients failing checkpoint blockade immunotherapy (CBI) may still benefit from TIL-ACT,” they added.

Side effects

When evaluating TILs with second-line CBI treatment options, the following factors need to be considered: availability of TIL-ACT, access, logistics, patient preference, performance status, and a balanced consideration of expected side effects and quality of life.

“For example, approximately half of the patients receiving the anti-CTLA-4/anti-PD-1 combination developed early onset of severe immune-mediated toxicity necessitating discontinuation, while a subset of patients experienced late-onset or long-lasting toxicity, with 35.7 percent probability of ongoing toxicity at 24 months,” the investigators said. [Eur J Cancer 2021;149:153-164]

On the other hand, toxicity with TIL-ACT did not usually last for a long period and was often associated with nonmyeloablative chemotherapy, according to the investigators.

“Furthermore, TIL-treated patients reported lower levels of fatigue, discomfort, and insomnia compared with those who received ipilimumab,” they added.