Nivolumab in Combination with R-CHOP for Treatment-Naïve Diffuse Large B-Cell Lymphoma: An Evaluation of Safety and Efficacy Open Access

• Addition of nivolumab to R-CHOP, using a priming approach, offers improved outcomes without unexpected toxicities even in high-risk disease.

• Evaluation of immune cell subsets offers insights into the mechanisms of efficacy and toxicity with the combination regimen.

Approximately 20% of diffuse large B-cell lymphoma have aberrations involving the PD-L1/PD-L2 locus. This justifies the investigation of PD-1 checkpoint inhibitors in the frontline therapy setting in a bid to improve outcomes especially in patients with high-risk disease (antecedent low-grade lymphoma, MYC aberrancy, advanced staged disease, and intermediate/high risk IPI score). This Phase 1b study evaluated the safety and preliminary efficacy of combination nivolumab and R-CHOP using a priming approach. Upon establishing the maximum tolerated dose of nivolumab, treatment consisted of a lead-in phase with nivolumab 240 mg x 1 followed 2 weeks later by combination nivolumab-R-CHOP given every 3 weeks for 6 cycles. A total of 33 patients were enrolled, of which 25 and 22 pts were evaluable for toxicity and efficacy, respectively. Estimated 18-month OS and PFS were 95.4% & 72.7%, respectively. The observed therapy-related adverse events were not significantly different from previous reports each nivolumab and R-CHOP, respectively. Patient reported outcomes did not suggest that the addition of nivolumab to R-CHOP led to worse quality of life measures. Exploratory analysis of biologic correlates showed an exhausted T cell immunophenotype to be a predictor of progression and immunotoxicity while also suggesting the effectiveness of priming approach. NCT03704714