Efficacy of immune checkpoint inhibitors for the treatment of metastatic melanoma (MM) in patients with concurrent chronic lymphocytic leukemia (CLL).
e22044 Background: Patients with CLL have immune impairment with abnormalities in T-cell subset composition and immune synapse formation. The impact of these defects on response to immune checkpoint inhibitors (CPI) is not known. Given the high incidence of melanoma in patients with CLL we sought to evaluate the response to CPI in patients with concomitant MM and CLL. Methods: Retrospective analysis of 24 patients (pts) with concurrent CLL and MM who received a total of 38 CPI therapies between July 1997 and July 2019. Primary objective was to determine objective response rate (ORR), defined as complete response (CR) or partial response (PR) by RECIST1.1. Secondary outcomes included event-free survival; overall survival (OS), and duration of response (DOR). Results: The median age at CLL and melanoma diagnosis was 62 and 63 years, respectively. 71% of patients were male. Most presented with early stage CLL at diagnosis (67%), 60% had mutated IGVH, and 47% had deletion of 13q by FISH. 71% remained on observation for their CLL. Median time from melanoma diagnosis to CPI initiation was 13.5 months. 83% had stage IV MM and 17% stage III MM at the time of therapy. 17% had increased LDH. The most common melanoma mutations were BRAF(35%), BRAFV600 (26%), TP53 (30%) and NRAS (26%). Median follow up was 37 months and the ORR was 24% (Table). Median DOR was 41 months and median OS is 26.4 months. Immune-mediated adverse events occurred in 42%, including 13% fever, 11% thrombotic events, 8% endocrine dysfunction. 13 pts are alive and 11 pts died (8 pts due to MM progression). There were no significant changes in absolute lymphocyte counts during CPI therapy. 2 pts received CPI while on ibrutinib or ibrutinib+venetoclax therapy with ongoing CLL responses. Conclusions: Our experience indicates that CPIs can be effective for the treatment of MM in patients with concurrent CLL, achieving durable responses. Immuno-mediated toxicities were frequently observed. A lower ORR was observed in first-line CPI in MM, however the numbers of pts are small. Further studies are needed to determine if initial or concurrent treatment for CLL could improve CPI outcomes and survival. Additional studies evaluating T cells function and tissue infiltration in these patients are ongoing. [Table: see text]