In a study presented by Radhakrishnan Ramchandren, MD, at the 23rd Congress of the European Hematology Association, the four-drug regimen of nivolumab plus doxorubicin, vinblastine, and dacarbazine (AVD) was a safe therapeutic combination in patients with newly diagnosed, advanced-stage classical Hodgkin lymphoma (HL).
Although frontline, multi-agent chemotherapy cures most newly diagnosed patients, “those with advanced-stage classical HL have suboptimal outcomes and the high toxicity of intensive regimens limits their use in older or frail patients,” Dr. Ramchandren, of the Barbara Ann Karmanos Cancer Institute at Wayne State University in Detroit, and colleagues noted. The anti-PD-1 immune checkpoint inhibitor nivolumab has demonstrated activity in patients with relapsed/refractory HL after failure of autologous hematopoietic cell transplantation, prompting researchers to evaluate the nivolumab combination in patients with previously untreated disease enrolled in the CheckMate 205 trial.
The analysis included 51 adult patients (median age = 37 years; range not reported) with advanced-stage HL (defined as stage III/IV or stage IIB with unfavorable risk factors). Patients received four doses of single-agent nivolumab 240 mg every two weeks, followed by nivolumab plus AVD combination therapy.
During a median follow-up of 11 months (range not provided), 49 patients (96%) completed nivolumab monotherapy and 45 (90%) completed combination therapy.
Thirty patients (59%) experienced a grade 3/4 treatment-related adverse event (AE) within 30 days of the last treatment dose (primary endpoint). The most common grade 3/4 AE was neutropenia (n=25; 49%), including five instances of febrile neutropenia (n=5; 10%), and the most common grade 3/4 immune-mediated AE was hepatitis (n=2; 4%). Eight patients (16%) developed treatment-related infections. No grade 5 treatment-related AEs occurred within 30 days of last treatment dose.
Four participants (8%) discontinued treatment due to an AE. One patient died during treatment, which was considered related to study drug toxicity.
The nivolumab combination was also effective in the newly diagnosed population: Eighty-four percent of patients responded to treatment, including 67 percent who had a complete response (per Independent Radiology Review Committee). The median time to therapy response was two months (range = 2-5 months) and the rate of nine-month progression-free survival was 94 percent (95% CI 82-98; p value not provided).
“This study demonstrates the safety profile of checkpoint inhibitor and chemotherapy combinations in the frontline therapy of HL, and opens the door for future studies evaluating comparative or combination studies with checkpoint inhibition,” Dr. Ramchandren noted. The role of checkpoint inhibitors in this patient population must also be viewed in light of recent data about the use of PET-adapted treatment strategies and the integration of brentuximab vedotin into frontline therapy. “Understanding how best to use all of these agents strategically will be the most important question we need to answer moving forward,” he said.
Ramchandren R, Domenech ED, Rueda A, et al. CheckMate 205 cohort D: a phase 2 trial of nivolumab for newly diagnosed advanced-stage classical Hodgkin lymphoma. Abstract #S114. Presented at the 23rd Congress of the European Hematology Association, June 15, 2018; Stockholm, Sweden.