Efficacy of Immune Checkpoint Inhibitors in Metastatic Melanoma (MM) Patients with Concurrent Chronic Lymphocytic Leukemia (CLL)

Context CLL patients have a high incidence of melanoma, and checkpoint inhibitors (CPI) are approved for treatment of patients with metastatic disease. However, patients with CLL are known to have a profoundly impaired immune system with various types of T-cell abnormalities, and the impact of these defects on response to (CPI) is not known. We sought to evaluate the response to treatment with CPI in patients with concomitant MM and CLL. Objective Primary objective included objective response rate (ORR) by RECIST1.1 criteria. Secondary outcomes included progression-free survival (PFS), overall survival (OS), and duration of response (DOR). Setting Retrospective study of patients with concurrent CLL and MM treated with CPI therapies at MD Anderson Cancer Center between 1997 and 2020. Patients Twenty-four patients were included, with a median age of 64 years. Seventy-one percent were male, 67% had early-stage CLL, and 71% were untreated. Thirty-three percent had prior melanoma treatment; 83% of patients had stage IV, and 17% had stage III melanoma. Interventions Thirty-eight CPI therapies were administered to 24 patients: single-agent PD-1 inhibitors pembrolizumab or nivolumab (53%), CTLA-4 inhibitor ipilimumab (29%), and combination therapies (18%). Results The ORR was 25% after first-line CPI and 21% for subsequent treatments, with a DOR of 50 and 16 months, respectively. After a median follow-up of 37 months, 12 patients died, 9 due to melanoma progression. The OS and PFS were 26 and 6 months, respectively. Increased LDH was associated with lower OS, and high LDH, and intermediate/high-risk CLL with a lower PFS. There were no significant changes in absolute lymphocyte counts during CPI. 2 patients received CPI while on ibrutinib or ibrutinib+venetoclax therapy with ongoing CLL responses. Conclusions CPIs are an effective treatment option for patients with MM and concurrent CLL, with a portion of patients able to achieve durable responses. A lower ORR was observed after first-line CPI; however, the number of patients in this group is small, and 33% of them had received prior treatments. Further studies are needed to determine if concurrent treatment for CLL could improve the efficacy of treatment with CPIs by reducing some of the disease-related immunodysfunction.