Background: Melanoma is one of the most common malignancies diagnosed during pregnancy. Little is known about the clinical outcomes of PAM, in particular, response to ICIs. We performed a retrospective study to assess this issue. Methods: A multicenter retrospective study was performed at 4 large melanoma centers. Patients (pts) with PAM treated with ICIs were identified and examined. Clinical data and molecular data (RNA sequencing, IHC) were explored. PAM was defined as development of advanced melanoma during pregnancy or within 2 years post-partum. Results: 19 pts with PAM were treated with ICIs. Median follow-up was 11.7 months (range 1.4 – 41.9 months). Median age was 29 years (range 16-36). Most pts had a cutaneous primary (N = 17, 89%) including the extremity (N = 8) or trunk (N = 7), and 5% were occult. 11 pts (58%) had a BRAF V600E mutation and 6 (32%) pts received BRAF/MEK targeted therapy. Most pts had prior primary melanoma (N = 12, 63%) and presented with advanced melanoma in the post-partum setting (N = 11, 58%). At advanced presentation, 6 (32%) pts were stage III/M1a and 13 (68%) pts were stage M1b/c/d; 7 (41%) pts had elevated LDH and 13 (68%) had visceral involvement. Among 11 patients treated with combination ipilimumab + anti-PD-1 therapy, 7 (64%) had objective responses (OR) with a 1-year progression free survival (PFS) of 40% and 1-year overall survival (OS) of 100%. By contrast, ICI monotherapy (3 with anti-PD-1/L1 and 4 with ipilimumab) was associated with poorer outcomes (OR in 25% and 33% for ipilimumab and anti-PD-1/L1, respectively). Molecular features (RNA sequencing, immunohistochemistry) will be presented. Conclusions: Patients with PAM represent a unique population and may particularly benefit with combination ICI therapy compared with ICI monotherapy (in a limited sample size). Molecular underpinnings of PAM biology are still being elucidated.