Phase 2 study of frontline brentuximab vedotin monotherapy in Hodgkin lymphoma patients aged 60 years and older.

Outcomes in older patients with Hodgkin lymphoma (HL) tend to be poor following conventional chemotherapy regimens. Treatment-related toxicity is significant and comorbidities often limit therapeutic options. This phase 2, open-label study evaluated the efficacy and safety of brentuximab vedotin, a CD30-directed antibody-drug conjugate, as frontline therapy in 27 HL patients aged ≥60 years. The objective response rate (ORR) was 92%, with 73% achieving complete remission. All patients achieved stable disease or better, and had decreased tumor volume following treatment. At the time of this analysis, the median duration of objective response for efficacy-evaluable patients (N = 26) was 9.1 months (range, 2.8 to 20.9+ months), median progression-free survival was 10.5 months (range, 2.6+ to 22.3+ months), and median overall survival had not been reached (range, 4.6+ to 24.9+ months). The observed adverse events (AEs) were generally consistent with the known safety profile of brentuximab vedotin. The most common AEs were peripheral sensory neuropathy (78%), fatigue (44%), and nausea (44%), and were ≤ grade 2 for most patients. The incidence of grade 3 peripheral neuropathy events was relatively high (30% overall), particularly among patients with the known risk factors of diabetes and/or hypothyroidism (46% vs 14% for those without). However, these risk factors were not associated with delayed time to resolution/improvement of peripheral neuropathy. Preliminary data showed no substantial age-related changes in brentuximab vedotin pharmacokinetics. Brentuximab vedotin monotherapy may provide a frontline treatment option for older patients who cannot tolerate conventional combination chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01716806.