Nivolumab Plus R-CHOP Shows Promising Efficacy and Tolerability for Newly Diagnosed DLBCL
Key Clinical Summary
- Population and Design: Phase 1b trial in 33 previously untreated patients with aggressive DLBCL evaluated nivolumab (240 mg priming dose) plus 6 cycles of R-CHOP every 21 days; median follow-up 11.6 months.
- Efficacy: Among evaluable patients, 18-month OS was 95.4% and PFS 72.7%, indicating promising survival outcomes with the nivolumab–R-CHOP priming approach.
- Safety: Grade 3 AEs in 88% of patients; common toxicities included fatigue (88%), hypertension (84%), and musculoskeletal disorders (64%). No excess general toxicity observed beyond expected immunologic effects, supporting further evaluation of this immune checkpoint–based frontline strategy.
The addition of nivolumab to standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy for previously untreated aggressive diffuse large B-cell lymphoma (DLBCL) using a priming approach demonstrated promising survival outcomes and manageable toxicity, according to study results published in Blood Advances.
Previous research has found immune checkpoint inhibitors, such as nivolumab, to be efficacious when combined with standard R-CHOP therapy for patients with DLBCL. Researchers have noted that 20 to 30% of patients with DLBCL will likely have aberrations involving the programmed death ligands 1 and 2 (PD-L1/PD-L2) locus, with T-cell exhaustion as a consequence.
“We investigated the frontline use of combination nivolumab and R-CHOP based on a significant proportion of untreated cases of DLBCL expected to have PD-L1/PD-L2 aberrations,” investigators explained. They added, “we deployed the principle of immune priming (treatment with nivolumab weeks before initiation of the combination regimen), and evaluated biologic correlates of efficacy and toxicity with this approach.”
Researchers conducted this phase 1b study to determine the maximum tolerated dose and efficacy of nivolumab and R-CHOP therapy for these patients. Treatment included this nivolumab priming dose (240 mg) followed by 6 21-day cycles of nivolumab plus standard R-CHOP.
The primary objective was the maximum tolerated dose and complete remission (CR) rate. Overall, 33 patients were included, of which, 25 patients were evaluable for toxicity and 22 for efficacy. The median follow-up was 11.6 months.The estimated 18-month overall survival (OS) was 95.4% and the estimated progression-free survival was 72.7%.
In terms of safety, grade 3 adverse events occurred in 88% of patients. The most common nonhematologic treatment-related adverse events were fatigue (88%), hypertension (84%), and musculoskeletal disorders (64%).
The researchers concluded, “The addition of nivolumab to R-CHOP for the treatment of newly diagnosed aggressive B-cell lymphoma has promising efficacy with complete response rates.”
They added, “There was no signal for increased general toxicities stemming from the addition of nivolumab, though immunotoxicity was common.”
Source:
Oluwatobi Odetola, Ma S, Winter JN, et al. Nivolumab in combination with R-CHOP for treatment-naïve diffuse large B-cell lymphoma: an evaluation of safety and efficacy. Blood Advances. Published online November 3, 2025. doi:10.1182/bloodadvances.2025016298
