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Nivolumab in combination with R-CHOP for treatment-naïve diffuse large B-cell lymphoma: an evaluation of safety and
Oluwatobi Odetola1, Shuo Ma1,2, Jane N Winter1,2
1Division of Hematology/Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Abstract:
Approximately 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.
Insights
Frontline nivolumab plus R-CHOP shows promising survival for diffuse large B-cell lymphoma patients. The combination therapy demonstrated good safety and did not worsen patient quality of life.
Area of Science:
- Oncology
- Immunotherapy
- Hematologic Malignancies
Background:
- Approximately 20% of diffuse large B-cell lymphoma (DLBCL) cases involve PD-L1/PD-L2 locus aberrations.
- PD-1 checkpoint inhibitors are being investigated for frontline therapy to improve outcomes in high-risk DLBCL patients.
Purpose of the Study:
- To evaluate the safety and preliminary efficacy of combining nivolumab (a PD-1 inhibitor) with R-CHOP chemotherapy in a frontline setting for DLBCL.
- To assess the impact of this combination on patient-reported outcomes and explore biologic correlates.
Main Methods:
- A Phase 1b study involving a priming approach with nivolumab followed by combination nivolumab-R-CHOP for 6 cycles.
- 33 patients were enrolled; 25 were evaluated for toxicity and 22 for efficacy.
- Patient-reported outcomes and biologic correlates were analyzed.
Main Results:
- Estimated 18-month overall survival (OS) was 95.4% and progression-free survival (PFS) was 72.7%.
- Therapy-related adverse events were comparable to historical R-CHOP data.
- Patient-reported outcomes did not indicate a decline in quality of life.
Conclusions:
- Frontline nivolumab combined with R-CHOP demonstrates encouraging safety and efficacy in DLBCL patients.
- An exhausted T cell immunophenotype may predict progression and immunotoxicity, supporting the priming approach's effectiveness.
