Resolution of malignant cutaneous lesions with brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large cell lymphoma

Background: Brentuximab vedotin (SGN-35) is an anti-CD30 antibody conjugated to the potent antimicrotubule agent, monomethyl auristatin E (MMAE), by a plasmastable linker. In a phase II study of brentuximab vedotin in 58 patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL), an objective response rate of 86% was observed by independent review. Aims: To describe the experience with brentuximab vedotin in relapsed or refractory sALCL patients with malignant cutaneous lesions who participated in a phase II, single-arm, multicenter study. Methods: Brentuximab vedotin 1.8 mg/kg was administered every 3 weeks as a 30- minute outpatient IV infusion for up to 16 cycles of treatment. Determination of antitumor efficacy was based on objective response assessments by independent review according to Cheson 2007; resolution of cutaneous lesions was assessed by the investigator. Results: Fifteen patients with relapsed or refractory sALCL who participated in the phase II study had malignant cutaneous lesions at baseline. Among these patients, the median age was 57 years (range, 33-70), and ECOG performance status was 0 or 1. Median number of prior therapies was 2 (range, 1-5) and 4 patients (27%) had an autologous stem cell transplant prior to the study. The majority of patients (80%) had ALK-negative disease. Complete resolution of malignant cutaneous lesions was achieved in 93% of patients (14/15) with a median time to resolution of all lesions of 4.9 weeks (range, 2.6-36). Objective responses were achieved by all patients (12 CR, 3 PR); median duration of objective response was 12.6 months. The most common adverse events (≥30%) of any grade among the 15 patients were diarrhea, pyrexia, constipation, nausea, peripheral sensory neuropathy, decreased appetite, fatigue, and rash; the majority of adverse events were grade 1/2 in severity. Conclusion: In a phase II trial of brentuximab vedotin in relapsed or refractory sALCL, local and systemic responses were observed among 15 patients who had malignant cutaneous lesions at baseline: 93% of patients achieved complete resolution of cutaneous lesions and 100% had objective responses. Adverse events were manageable, and the safety profile was comparable to that observed among patients without cutaneous involvement. These results warrant further study of brentuximab vedotin in patients with CD30-positive cutaneous lymphomas.