Nivolumab in combination with R-CHOP for treatment-naïve diffuse large B-cell lymphoma: an evaluation of safety and efficacy.

abstractApproximately 20% of diffuse large B-cell lymphoma have aberrations involving the programmed death ligands 1 and 2 (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 International Prognostic Index score). This phase 1b study evaluated the safety and preliminary efficacy of a combination of nivolumab and R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) using a priming approach. Upon establishing the maximum tolerated dose of nivolumab, treatment consisted of a lead-in phase with nivolumab 240 mg × 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 patients were evaluable for toxicity and efficacy, respectively. Estimated 18-month overall survival and progression-free survival rates were 95.4% and 72.7%, respectively. The observed therapy-related adverse events were not significantly different from previous reports on 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 a priming approach. This trial was registered at www.clinicaltrials.gov as #NCT03704714.