Nivolumab in combination with brentuximab vedotin had a high response rate in patients with relapsed/refractory primary mediastinal B-cell lymphoma (PMBL), according to results of the open-label, multicenter, phase II CheckMate 436 study published in the Journal of Clinical Oncology.
The CheckMate 436 study was a phase I/II trial that enrolled adult patients with relapsed/refractory non-Hodgkin lymphoma and included a dose-escalation cohort and expansion cohort. Only the expansion cohort data for relapsed/refractory PMBL were reported in the journal article.
A total of 30 patients were enrolled in the expansion cohort for relapsed/refractory PMBL to receive nivolumab and brentuximab vedotin. Enrolled patients previously received autologous hematopoietic cell transplantation or, if ineligible for transplantation, at least two prior chemotherapy regimens.
Patients had a median age of 35.5 years (range, 19 to 83 years of age). Most patients were white (87%) and approximately half were female (57%). Patients received a median of 2 lines of prior therapy (range, 2 to 5), and 4 patients (13%) received prior autologous hematopoietic cell transplantation. At the time of study analysis, 29 received nivolumab and 30 received brentuximab vedotin.
The trial met its primary endpoint, showing that at a median follow-up of 11.1 months, investigator-assessed overall response rate was 73% (95% CI, 54–88), which included 11 (37%) complete responses (CR) and 11 (37%) partial responses. A post hoc analysis with blinded independent central review revealed an ORR of 70% (95% CI, 51–85) and a 43% CR rate.
“The efficacy is quite striking,” Premal Lulla, MBBS, assistant professor of hematology - oncology at the Center for Cell and Gene Therapy at Baylor College of Medicine in Houston, told Cancer Network. “The combination has been synergistic rather than additive or individually effective.”
However, he noted, longer follow-up is needed.
“As it stands, the follow-up duration is not enough to make any assumptions of how the patients did—whether some of them, or a subset at least, were cured or not,” he said.
Given that there are no standard treatments for this patient population, Lulla said that this combination is being used off-label for certain patients.
A total of 25 patients (83%) had a treatment-related adverse event of any grade, with the most common being neutropenia (30%) and peripheral neuropathy (27%). All of the patients who had neutropenia had grade 3 or 4 severity and 10% of patients who had peripheral neuropathy had grade 3 or 4 severity. Approximately half of patients (53%) had a grade 3 or 4 event.
Lulla commented that the safety profile shows the adverse events one might expect with this combination, but one aspect that surprised him was the incidence of immune-related adverse events were lower than what he had expected. There was one case of grade 4 immune-mediated hepatitis, one case of grade 3 colitis, and one case of grade 3 maculopapular rash.
“With Nivo you see at least 20% of patients who have some form of immune related grade 3 or higher adverse events,” Lulla said. “So that’s encouraging.”