Therapeutic advantages of thymosin α1 combined with toripalimab for elderly patients with advanced melanoma: Preliminary results from a phase II study.

Abstract

e21524 Background: Anti-PD-1 antibodies show limited response rates in Chinese melanoma patients, necessitating combination therapies to enhance efficacy. Elderly patients often have multiple comorbidities, complicating the balance between therapeutic benefits and toxicities. Additionally, age-related declines in naïve T-cell numbers and immunosenescence may impact the effectiveness and safety of immunotherapy. Thymosin α1 (Tα-1) promotes T-cell generation, proliferation, activation, and survival, increasing lymphocyte counts. It also helps maintain immune homeostasis in cases of excessive inflammation, potentially reducing immune-related side effects.This study aims to evaluate the efficacy and safety of Tα-1 in combination with toripalimab in elderly patients with advanced melanoma. Methods: A prospective cohort of nine stage IV melanoma patients was enrolled between July 5, 2023, and May 7, 2024. Each patient received up to four cycles of combination therapy with Tα-1 (1.6 mg daily during the first week, then three times weekly for the next two weeks) and toripalimab. After four cycles, patients continued on toripalimab until disease progression or intolerable toxicity. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Results: The median age was 74 years (range 60–81), with five males and four females. Eight patients had acral melanoma, and one had an unknown primary origin. All patients had at least one chronic underlying condition, and seven had an ECOG performance status of ≥2. The median follow-up was 9.9 months (8.3–16.0 months). The ORR was 22.2%, and the disease control rate (DCR) was 77.8%. Median PFS was 8.2 months, while median OS was not reached. Adverse events occurred in three patients, all grade 1 per CTCAE 4.0: two cases of vitiligo and one case of elevated transaminases. Non-progressive disease (non-PD) patients had lower neutrophil-to-lymphocyte ratios and higher lymphocyte percentages during treatment compared to PD patients. Conclusions: The combination of Tα-1 and toripalimab demonstrated significant efficacy with a favorable safety profile in elderly patients with advanced melanoma. These findings suggest a promising therapeutic strategy for this population. Larger clinical trials are needed to validate these results and elucidate the underlying mechanisms.