Temozolomide and nivolumab in patients with refractory metastatic melanoma (MM).

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e21521 Background: Immune checkpoint inhibitors (ICI) are the standard treatment for patients (pts) with MM. However, only a subset of pts respond to ICIs. Temozolomide (TEM) is used in refractory settings but with low objective response rates and no clear overall survival benefit. The efficacy of combined ICI + TEM is not well described. Methods: This was a single center, retrospective study of pts with MM who received treatment with nivolumab (NIVO) and TEM or TEM alone between 11/6/2013 and 11/6/2023. Demographic information, disease characteristics, LDH, treatment, toxicity, objective response, and outcomes were collected. Results: 34 patients were included. 16 were treated with NIVO + TEM and 18 were treated with TEM alone. In the NIVO + TEM group, 81% were male (n = 13) with median age of 59.5 years (range 20-79), and in the TEM group, 56% were male with median age 61 (range 35-81). For NIVO + TEM, 31% had partial response (PR; n = 5), 6% had stable disease (SD, n = 1), and 63% had progressive disease (PD; n = 10). For TEM, 11% had PR (n = 2), 22% had SD (n = 4), and 67% had PD (n = 12) (p = 0.37). For NIVO + TEM, 2 PRs were durable, ongoing at 442 and 741 days; 3 PRs were transient (85-179 days); 1 pt had durable SD ongoing at 201 days. For TEM, PR durations were 173 and 504 days, and SD durations between 213-435 days. Five pts with PD treated with NIVO + TEM had mixed responses (31%) compared with 1 pt treated with TEM (6%). Median progression free survival (PFS) was 80 days (range 11-748) for NIVO + TEM and 55.5 days (7-415) for TEM (p = 0.31). Median overall survival (OS) was 160 days (43-363) for NIVO + TEM and 118 days (7-1938) for TEM (p = 0.15). There were 26 adverse events (AEs) for NIVO + TEM (27% grade 1, 42% grade 2, 19% grade 3, and 12% grade 4; thrombocytopenia and pneumonitis), and 25 AEs for TEM (40% grade 1, 40% grade 2, 12% grade 3, and 8% grade 4; thrombocytopenia) [p = 0.64]. Conclusions: NIVO + TEM occasionally produced durable responses, although outcome metrics were not clearly superior to TEM alone in this small study. Further studies should quantify the benefit of ICI + chemotherapy regimens in refractory MM. [Table: see text]