Recent clinical trial results have suggested efficacy and tolerable safety for the combination of nivolumab with brentuximab vedotin (BV) when given to patients with relapsed/refractory mediastinal gray zone lymphoma (MGZL). These results were presented at the 61st Annual Scientific Meeting of the British Society for Haematology by Armando Santoro, MD, of Humanitas University in Milano, Italy, and colleagues.
The study results reflected outcomes from the MGZL cohort of the open-label, phase 1/2 CheckMate 436 trial (ClinicalTrials.gov Identifier: NCT02581631). Patients had been previously treated with either high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HCT) or 2 or more multi-agent chemotherapy regimens in patients who were ineligible for autologous HCT. Treatment was given until disease progression or unacceptable toxicity and consisted of intravenous nivolumab 240 mg every 3 weeks and BV given intravenously at 1.8 mg/kg every 3 weeks. The primary study endpoints were investigator-assessed objective response rate (ORR), using Lugano 2014 criteria and continuous safety evaluation.
A total of 10 patients were evaluated in this analysis. The patients received a median of 7 doses of each study drug, and the investigator-assessed ORR was 70% at the median follow-up of 12.4 months. Complete response (CR) was seen in 5 (50%) of the patients, with a time to CR of 1.2 to 4.8 months. The 6-month rate of overall survival (OS) was 80% (95% CI, 40.9%-94.6%), and the median OS was not reached. Patients who reached CR were bridged to subsequent HCT.
Any-grade treatment-related adverse events (TRAEs) were reported in 9 of the 10 patients in this study, and 3 patients had a grade 3 TRAE. Neutropenia and paresthesia were the most common any-grade TRAEs. Neutropenia and thrombocytopenia occurred at grade 3 in 1 patient each, and a serious TRAE of grade 3 febrile neutropenia was reported in 1 patient.
An immune-related grade 2 maculopapular rash was reported in 1 patient, and 1 patient had a grade 1 infusion-related reaction. No grade 4 TRAEs occurred during the study. A total of 3 fatalities occurred, all of which were attributed to disease progression.
The study investigators concluded that the combination of nivolumab plus BV in the relapsed/refractory MGZL cohort of this trial showed a high investigator-assessed ORR, and that the results were consistent with those of the classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma cohorts of the study.
The investigators also considered the safety profile to be tolerable and consistent with prior reports, and they suggested that this treatment combination has potential as a bridge therapy to HCT in patients with disease that is refractory to chemotherapy.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Santoro A, Moskowitz AJ, Ferrari S, et al. CheckMate 436: primary efficacy and safety analysis of the phase 2 study evaluating nivolumab combined with brentuximab vedotin for relapsed/refractory mediastinal gray zone lymphoma. Poster presented at: 61st Annual Meeting of the British Society for Haematology; April 25-28, 2021; virtual.