859P The influence of hematologic malignancies on response to immune checkpoint inhibition in patients with advanced melanoma

Patients diagnosed with hematologic malignancies (HM) have a higher risk of developing subsequent solid tumors, such as melanoma. Patients with HM were mostly excluded from clinical trials but could derive less benefit from immune checkpoint inhibition due to disease or treatment-related T- or B-cell dysfunction. All advanced stage IIIc and IV melanoma patients treated with anti-PD-1 or ipilimumab-nivolumab between 2015 and 2021 were included from the prospective nationwide Dutch Melanoma Treatment Registry. Progression-free survival (PFS), overall survival (OS), and melanoma-specific survival (MSS) were analyzed for patients with HM (HM+) and without HM (HM-). A cox model was used to account for confounders associated with PFS and OS. Fifty-seven HM+ patients and 2506 HM- patients were included. Twenty-two patients were diagnosed with leukemia, 26 with malignant lymphoma, three with multiple myeloma, and six had a different type of HM. Forty-four percent received curative treatment for their HM. In the anti-PD-1 cohort, median PFS was 2.8 months for HM+ and 9.9 months for HM- (p=0.01). MSS was 41.2 months for HM+ and 58.1 months for HM- (p=0.00086). In multivariable analysis, the presence of a HM was significantly associated with a higher risk of melanoma progression (HRadj 1.68; 95%CI 1.24-2.29; p<0.001) and death (HRadj 1.76; 95%CI 1.25-2.47; p<0.001). Median PFS, OS, and MSS for anti-PD-1 and ipilimumab-nivolumab can be seen in the table.Table: 859PMedian progression-free survival, overall survival, and melanoma-specific survival in months, stratified by hematologic malignancy and treatment typeMedian PFS in months (95% CI)Median OS in months (95% CI)Median MSS in months (95% CI)Anti-PD-1 and HM+ (n=46)2.8 (2.6-7.3)12.8 (6.2-NR)41.2 (12.8-NR)Anti-PD-1 and HM (n=1717)9.9 (8.6-11.8)31.0 (28.5-35.0)58.1 (47.5-NR)Ipilimumab-nivolumab and HM+ (n=11)2.3 (2.0-NR)4.6 (2.4-NR)4.6 (2.4-NR)Ipilimumab-nivolumab and HM- (n=789)6.9 (5.5-9.2)31.7 (22.1-39.0)46.1 (33.4-NR) Open table in a new tab Patients with hematologic malignancy and advanced melanoma show significantly worse melanoma-related survival than patients with advanced melanoma alone. Larger numbers of patients are needed to look into the different subtypes of HM.