Nearly three-quarters of patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBL) responded to treatment with nivolumab plus brentuximab vedotin, according to findings presented at the 24th Congress of the European Hematology Association.
The authors, led by Pier Luigi Zinzani, MD, PhD, from the University of Bologna in Italy, also noted that the safety profile of this combination was consistent with the safety profile of either agent alone.
The open-label, phase I/II CheckMate436 trial evaluated nivolumab plus brentuximab vedotin in patients with relapsed/refractory PMBL who had received either high-dose conditioning chemotherapy and autologous hematopoietic cell transplantation (AHCT) or two or more multi-agent chemotherapy regimens.
Dr. Zinzani reported results from 30 patients (median age = 35.5 years; range = 19-83 years) who had been treated with the nivolumab combination. Participants had received a median of two prior systemic therapies (range = 2-5) and four patients (13%) had received prior AHCT.
Per study protocol, patients received nivolumab 240 mg plus brentuximab vedotin 1.8 mg/kg every three weeks until disease progression or unacceptable toxicity.
After a median follow-up of 11.1 months (range not reported), 25 patients were eligible for response. The overall response rate (the study’s primary endpoint) was 73%, which included:
- 11 patients with complete remission
- 10 patients with partial remission
As of data presentation, the median duration of response had not been reached.
The results suggest that brentuximab vedotin and nivolumab, an anti−PD-1 immune checkpoint inhibitor, work synergistically to target CD30 expression and programmed death-1 (PD-1) ligand expression that are characteristic features of PMBL, the investigators explained.
Most patients (n=25/30; 83%) experienced at least one treatment-related adverse event (AE). The most frequently reported treatment-related AEs were neutropenia (30%), peripheral neuropathy (27%), peripheral sensory neuropathy (13%), thrombocytopenia (13%), rash (13%), and hyperthyroidism.
Sixteen patients (53%) experienced a grade 3/4 treatment-related AE, including:
- neutropenia (n=9; 30%)
- thrombocytopenia (n=3; 10%)
- peripheral neuropathy (n=3; 10%)
Four patients (13%) experienced a serious treatment-related AE, which included grade 3/4 colitis, maculopapular rash, or immune-mediated hepatitis.
The observed AEs “were consistent with the safety profiles of nivolumab and brentuximab vedotin treatment alone,” the authors reported.
The findings from this phase II study are limited by the lack of a comparator arm. The reliance on investigator-assessed outcomes, instead of review from an independent investigator, also may have limited the implications of the study’s findings.
The authors report relationships with Bristol-Myers Squibb, which sponsored the study.
Zinzani PL, Santoro A, Gritti G, et al. Nivolumab combined with brentuximab vedotin for relapsed/refractory primary mediastinal large B-cell lymphoma: efficacy and safety results from the phase 2 CHECKMATE 436 study. Abstract #S1601. Presented at the 24th European Hematology Association Annual Congress, June 16, 2019; Amsterdam, The Netherlands.