Brentuximab vedotin in the treatment of relapsed CD30 positive cutaneous lymphoma - results of an international, open label, randomised, phase 3, multicentre trial - ALCANZA
Abstract
Cutaneous T-cell lymphoma are rare, in advance stage almost incurable disease, treatment options in advance stage of the disease are limited. In randomised, open - label, multicentric clinical phase 3 study (ALCANZA) it has been compared effect of brentuximab vedotin (BV) in dose 1.8 mg/kg once every 3 weeks and investigator's choice (IC) - oral methotrexate 5-50 mg once weekly or bexarotene 300 mg/m2 once per day) - both drugs for up to 48 weeeks.
Primary endpoint of study was to assess objective response lasting at least 4 months (ORR4). Between AUG-2012 and JUL-2015, total of 131 patients (66 in BV arm and 67 in IC arm) has been enrolled.
At a median follow-up of 33.9 months, 60.9% of patients in BV and 7,8% in IC arm achived ORR4. The difference between arms was 53.1% (95% CI 36.5-67.2), p<0.001.
Median progression free survival was 15.8 months vs. 3.6 months favouring the BV arm (HR=0.373, 95% CI: 0.245-0.569; p<0.001). Grade 3 and 4 toxicity was observed in 27 of patients in BV arm (41%) and in 29 of patients in IC arm (47%).
Peripheral neuropathy was seen in 44 (67%) of patients treated with BV, only in 6 of them (10%) grade 3. Neuropathy resolved or improved in 38/44 (86%) of patients considering this adverse event as reversible.
These data supportthe recent FDA and EMEA approval of BV for the reatment of relapsed CD30+ cutaneous T-cell lymphoma after minimum of one line of previsous systemic treatment.