Brentuximab vedotin plus nivolumab was well tolerated and active in older patients with previously untreated Hodgkin lymphoma (HL) with comorbidities; however, the trial did not meet its prespecified activity criteria, according to results of a phase 2 clinical trial published in The Lancet Haematology.
Though HL is potentially curable with standard therapy, older patients tend to experience poorer outcomes and greater toxicity compared with younger patients. Therefore, Bruce Cheson, MD, of the Lymphoma Research Foundation in New York, New York, and colleagues at 8 cancer centers evaluated the efficacy and safety of brentuximab vedotin plus nivolumab (IV, 1.8 mg/kg and 3 mg/kg, respectively; every 21 days for 8 cycles) in untreated older patients (>60 years) with HL or in younger patients who were unsuitable for standard therapy (Eastern Cooperative Oncology Group performance status, 0-2) in a single-arm, phase 2 trial (ClinicalTrials.gov Identifier: NCT02758717). The primary endpoint was the overall response (partial metabolic response or complete metabolic response) at the end of 8 cycles of treatment.
Between May 13, 2016, and January 30, 2019, 46 patients (median age, 71.5 years; with 2 patients <60 years) enrolled in the study. The median follow-up duration was 21.2 months (IQR, 15.6-29.9). Most patients (76%) completed all 8 cycles of treatment.
For 25 evaluable patients at the interim analysis (October 11, 2019), the overall response rate was 64% (95% CI, 43-82). A complete and partial metabolic response was achieved in 52% and 12%, respectively. Because the trial failed to meet the prespecified activity criteria, the trial was closed to accrual on October 14, 2019.
For the final analysis of 46 evaluable patients, 48% and 13% of patients achieved a complete and partial metabolic response, respectively, for an overall response rate of 61% (95% CI, 45-75).
In total, 24% of patients discontinued treatment early: 2 patients refused treatments, 6 patients discontinued due to adverse events, 1 patient discontinued due to disease progression, 1 patient discontinued due to physician’s discretion, and 1 patient discontinued due to mortality. Dose adjustments were made for 30% patients, primarily due to neurotoxicity. Peripheral neuropathy occurred in 48% of patients (grade 3, 5 patients). Grade 4 adverse events occurred in 4 patients (increased aminotransferases, 1 patient; increased lipase or amylase, 2 patients; pancreatitis, 1 patient). The mortality (1 patient) was due to cardiac arrest, which may have been treatment related.
The project overall response rate at the interim analysis was expected to be 80%; the authors speculated that this rate may not have been achieved due to the comorbidities of the patients this study, leading to toxicities, dose modifications, and delays. Additionally, the treatment duration was only 8 cycles.
“Although the overall response rate at the completion of treatment was lower than projected, the study showed that select patients with Hodgkin lymphoma can derive long-term benefit from a non-chemotherapeutic regimen with long-term progression-free survival, especially those who achieved a complete metabolic response,” wrote the authors.
Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Cheson BD, Bartlett NL, LaPlant B, et al. Brentuximab vedotin plus nivolumab as first-line therapy in older or chemotherapy-ineligible patients with Hodgkin lymphoma (ACCRU): a multicentre, single-arm, phase 2 trial. Lancet Haematol. Published online October 1, 2020. doi:10.1016/s2352-3026(20)30275-1