The safety and tolerability of PD-1/PDL-1 inhibitors in hematologic malignancies: A meta-analysis.

Abstract

e14131 Background: The safety of programmed death receptor and ligand-1 (PD-1/PDL-1) inhibitors in hematologic cancers is not well-defined. We conducted a meta-analysis to investigate their safety. Methods: Pubmed & Cochrane databases were searched from 1968-2018. Full-text articles of clinical trials reporting treatment-related adverse events (AE) of PD-1/PDL-1 inhibitors in hematologic cancers were included. Incidences of all-grade and high-grade (≥grade 3) AEs were pooled and generated with a 95% confidence interval (CI) using a random effect model on STATA. Results: Eight studies (5 nivolumab & 3 pembrolizumab) were identified, with 703 patients and the median age of 34. Six studies were done in patients with relapsed/refractory (R/R) classical Hodgkin Lymphoma, one in R/R diffuse large B-cell lymphoma and one in combined hematologic cancers. There were 1092 total AEs, with a pooled high grade AEs rate of 13% (95% CI 9-17%). High-grade AEs (HAE) are summarized in the Table. Lipase elevation was the most common HAE for nivolumab (pooled incidence of 13%; 95% CI 6-23%), whereas leukopenia was the most common HAE reported with pembrolizumab use (pooled incidence of 36%; 95% CI 10-65%) There were 47 treatment discontinuation due to treatment-related AE. For Nivolumab, there was one treatment-related death (of a heavily pretreated patient) due to fatal pneumonitis. Conclusions: PD-1/PDL-1 inhibitors are well-tolerated in hematologic malignancies with a favorable risk of adverse events and very low treatment-related mortality. The HAE profile of Nivolumab differs from Pembrolizumab, and future studies should assess this heterogeneity further. [Table: see text]