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  • Efficacy and safety results...
    Armand, Philippe; Janssens, Ann; Gritti, Giuseppe; Radford, John; Timmerman, John; Pinto, Antonio; Mercadal Vilchez, Santiago; Johnson, Peter; Cunningham, David; Leonard, John P.; Rodig, Scott J.; Martín-Regueira, Patricia; Sumbul, Anne; Samakoglu, Selda; Tang, Hao; Ansell, Stephen M.

    Blood, 02/2021, Letnik: 137, Številka: 5
    Journal Article

    Nivolumab, an anti–programmed death-1 (PD-1) monoclonal antibody, showed promising activity in relapsed or refractory (R/R) follicular lymphoma (FL) in a phase 1 study. We conducted a phase 2 trial to further evaluate its efficacy and safety in patients with R/R FL and to explore biomarkers of response. Patients with R/R FL and at least 2 prior lines of therapy, each containing a CD20 antibody or an alkylating agent, were treated with nivolumab 3 mg/kg every 2 weeks. The primary end point was objective response rate (ORR) assessed by an independent radiologic review committee. Biomarker analyses included gene expression profiling and multiplex immunofluorescence studies of pretreatment tumor samples. A total of 92 patients were treated. After a minimum follow-up of 12 months, ORR was 4% (4 of 92 patients). Median progression-free survival (PFS) was 2.2 months (95% confidence interval CI, 1.9-3.6 months). Median duration of response was 11 months (95% CI, 8-14 months). Exploratory analyses suggested that responders had significantly higher proportion of CD3+ T cells in the tumor microenvironment than nonresponders, but no significant differences in PD-1 or programmed death-ligand 1 expression were observed. High expression of a set of tumor-associated macrophage genes was associated with reduced PFS (hazard ratio, 3.28; 95% CI, 1.76-6.11; P = .001). The safety profile was consistent with previous reports of nivolumab. In conclusion, nivolumab monotherapy was associated with very limited activity in patients with R/R FL. Better understanding of the immune biology of this disease may facilitate the development of effective checkpoint-based strategies. This trial was registered at www.clinicaltrials.gov as #NCT02038946. •Nivolumab monotherapy was associated with very limited activity in patients with R/R FL.•Understanding the tumor microenvironment may be necessary to develop effective checkpoint-based strategies in FL. Display omitted