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

Abstract

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.

© 2015 by The American Society of Hematology.

Figures

Figure 1

Maximum tumor size reduction from baseline. All 26 efficacy-evaluable patients achieved tumor reduction. Tumor size was assessed by measurement of index lesions on CT scans, whereas overall response (indicated by the color of the bars) was based on the Revised Response Criteria for Malignant Lymphoma, which incorporates both CT and PET scan results.

Figure 2

PFS for all patients and for patients with CR. (A) Median PFS was 10.5 months (range, 2.6+ to 22.3+ months) in all efficacy-evaluable patients (N = 26). (B) Median PFS was 11.8 months (range, 4.1 to 22.3+ months) in patients with CR (n = 19). Censored patients are indicated by open circles (○).