The U.S. Food and Drug Administration (FDA) granted priority review to the anti-CD30 monoclonal antibody brentuximab vedotin (BV) for the treatment of cutaneous T-cell lymphoma (CTCL).
The decision was based on results from the international, open-label, phase III ALCANZA trial, which included 128 patients with CD30-expressing mycosis fungoides (n=97) or primary cutaneous anaplastic large-cell lymphoma (ALCL; n=31), both common subtypes of CTCL. Patients were randomized 1:1 to receive BV 1.8 mg/kg once every three weeks for up to 48 weeks (n=64; median age = 62 years; range not provided) or physician’s choice of either methotrexate 5 to 50 mg once-weekly or bexarotene 300 mg/m2 once-daily (control group; n=64; median age = 59 years; range not provided).
BV induced responses lasting four or more months (primary endpoint) in 56 percent of patients, compared with 12.5 percent of patients receiving physician’s choice of therapy (p<0.0001).
At a median follow-up of 22.9 months, the median progression-free survival (PFS) was 16.7 months for BV-treated patients versus 3.5 months for the control group (hazard ratio [HR] = 0.270; 95% CI 0.169-0.430; p<0.0001). The overall response rate (ORR) was 67 percent (n=43) with BV and 20 percent (n=13) with the control therapies (p<0.0001); complete response (CR) rates were 16 percent and 2 percent, respectively (p=0.0046).
Grade ≥3 adverse events (AEs) were observed in 41 percent of BV-treated patients and 47 percent of control patients; serious AEs occurred in 29 percent of patients in each arm. Peripheral neuropathy occurred in significantly more patients treated with BV (67% vs. 6%; p value not reported). The most common any-grade AEs in both the BV and control cohorts included nausea (36% and 13%), diarrhea (29% and 6%), fatigue (29% and 27%), vomiting (17% and 5%), alopecia (15% and 3%), pruritus (17% and 13%), pyrexia (17% and 18%), decreased appetite (15% and 5%), and hypertriglyceridemia (2% and 18%).
Twenty-four percent of BV-treated patients experienced AEs that led to treatment discontinuation, compared with 8 percent of patients in the control arm (p value not reported). Four deaths were reported in the BV cohort, three of which were deemed unrelated to treatment.
The FDA’s decision on the drug’s approval is expected on or before December 16, 2017.
The drug is already approved for the treatment of Hodgkin lymphoma and systemic ALCL.
Sources: Seattle Genetics press release, August 16, 2017; Kim YH, Whittaker S, Horwitz SM, et al. Brentuximab vedotin demonstrates significantly superior clinical outcomes in patients with CD30-expressing cutaneous T cell lymphoma versus physician’s choice (methotrexate or bexarotene): the phase 3 ALCANZA study. Abstract #182. Presented at the 2016 ASH Annual Meeting, December 4, 2016; San Diego, CA.