Efficacy of immune checkpoint inhibitors for the treatment of advanced melanoma (AM) in patients with concomitant chronic lymphocytic leukemia (CLL).

Abstract

e19511 Background: CLL is the most prevalent adult leukemia and is associated with an increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICI in patients with CLL. Immune checkpoint inhibitors (ICI) have revolutionized management of AM, but data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. We, therefore, sought to examine the efficacy of ICI for melanoma in patients with concomitant CLL and AM. Methods: In this international and multicentre retrospective study, review of clinical databases identified patients with concomitant CLL and AM treated with ICI from two US tertiary cancer centers (n = 39) and an Australian multi-institutional experience (AUS, n = 19). Objective response rates (ORR), defined as complete or partial response by RECIST v1.1, and survival outcomes (overall survival, OS, and progression-free survival, PFS) among patients with CLL and AM were assessed. Clinical factors associated with improved ORR and survival were explored. Results: Between 1997 and 2020, 58 patients with CLL were treated with ICI for concomitant AM. Among all patients with CLL and AM, ORR to ICI was 41% and median duration of response was 18 months. A majority were untreated for CLL (64%) at the time of ICI. Patients with prior history of treatment for CLL had significantly reduced ORRs (21% vs 51%, p = 0.04), PFS (3.6 vs. 14.6 months, p = 0.005), and OS (7.4 vs. 52.2 months, p = 0.002), compared to patients on observation for their CLL. Prior treatment with T-lymphocyte depleting chemoimmunotherapy (fludarabine, bendamustine, and alemtuzumab) was particularly associated with poor outcomes (median OS of 7.0 months, median PFS of 3.4 months). On univariate analysis, prior treatment for CLL, high risk CLL 17p deletion, and higher CLL Rai stage were associated with shorter PFS from ICI, though CLL treatment was the only factor independently associated with shorter PFS in the multivariate model (HR 6.5, [CI 2.1-20.3], p = 0.001]. Overall, 3 patients developed CLL progression while on ICI, though in two of these patients, the AM had an objective, durable clinical response to ICI. Overall, immune-related adverse events (irAE) occurred following 38% of ICI and rates of irAE were similar by CLL treatment status. Conclusions: Our case series of patients with concomitant CLL and melanoma demonstrate frequent, durable clinical responses to ICI However, those with prior chemoimmunotherapy treatment for CLL had significantly worse outcomes. We found that CLL disease course is largely unchanged by treatment with ICI.