San Diego, CA—Brentuximab vedotin (Adcetris) monotherapy significantly improved the objective response rate (ORR) lasting ≥4 months compared with the investigator’s choice of standard therapy in patients with cutaneous T-cell lymphoma (CTCL), reported Youn H. Kim, MD, Director, Multidisciplinary Cutaneous Lymphoma Clinic, Stanford University School of Medicine, CA, at the 2016 American Society of Hematology meeting.
The end point of ORR lasting ≥4 months was a measure of clinically meaningful efficacy, which combines the response rate and the duration of response in a single end point. The ORR was determined by a global response of all compartments using consensus criteria for skin evaluation, radiographic assessment, and circulating Sézary cell assessment, as determined by an independent review.
Approximately 5 times as many patients who were randomized to receive brentuximab vedotin achieved an ORR lasting ≥4 months compared with those who received standard therapy.
“These compelling results have potential practice-changing implications for the use of brentuximab vedotin in managing patients with CD30-expressing cutaneous T-cell lymphoma who require systemic therapy,” said Dr Kim.
Current systemic therapies for CTCL rarely provide reliable or durable responses, Dr Kim added. Brentuximab vedotin showed significant clinical activity in CTCL in 2 phase 2 clinical trials. As a result, the randomized phase 3 ALCANZA clinical trial investigated the safety and efficacy of brentuximab vedotin, a CD30-targeting antibody–drug conjugate, versus physician’s choice of methotrexate or bexarotene in patients with previously treated CD30-expressing CTCL.
“This is the first reported phase 3 study of a new systemic agent tested against standard therapy in cutaneous T-cell lymphoma,” said Dr Kim.
The ALCANZA Clinical Trial
In the ALCANZA clinical trial, patients with CD30-expressing CTCL, including those with primary cutaneous anaplastic large-cell lymphoma (ALCL) or mycosis fungoides, were randomized to brentuximab or to investigator’s choice of methotrexate or bexarotene (standard therapy).
The study randomized 131 patients, with 128 patients in the intent-to-treat population (97 patients with mycosis fungoides, 31 patients with primary cutaneous ALCL). Patients were enrolled at 52 sites globally. Patients in the brentuximab vedotin group received brentuximab 1.8 mg/kg intravenously every 3 weeks. The treatment duration in both treatment arms was up to 16 3-week cycles until disease progression or until intolerable toxicity.
Stage IV visceral disease was more common at baseline in patients who received brentuximab vedotin than in patients who received standard therapy (67% vs 61%, respectively), and extracutaneous disease was more common in patients with primary cutaneous ALCL who received brentuximab vedotin than in patients who received standard therapy (44% vs 27%, respectively).
Treatment with brentuximab vedotin resulted in significant improvement in ORR lasting ≥4 months (56.3%) versus treatment with standard therapy (12.5%; P <.0001).
All the key secondary end points favored brentuximab vedotin. The complete response rate was 15.6% with brentuximab vedotin versus 1.6% with standard therapy (P = .0046), and the median progression-free survival was 16.7 months versus 3.5 months (hazard ratio, 0.270; P <.0001), respectively. The mean maximum reduction in the Skindex-29 symptom domain was 27.96 points with brentuximab vedotin versus 8.62 points with standard therapy (P <.0001).
The ORR lasting ≥4 months in patients with mycosis fungoides was 50% with brentuximab vedotin versus 10% with the standard therapy. Responses were superior with brentuximab vedotin over standard therapy in all clinical stages of mycosis fungoides.
In patients with primary cutaneous ALCL, the ORR rates were 75% with brentuximab versus 20% with standard therapy. The ORR lasting ≥4 months in patients with primary cutaneous ALCL with extracutaneous disease was 57% in the brentuximab group versus 0% in the standard-therapy group.
The skin response rates were superior with brentuximab vedotin over standard therapy in both patient subgroups.
Brentuximab vedotin’s safety profile was consistent with its established tolerability profile. Serious adverse events were reported in 41% of patients who received brentuximab vedotin compared with 47% of patients who received standard therapy. As expected, more patients discontinued brentuximab vedotin than standard therapy (24% vs 8%, respectively), primarily because of peripheral neuropathy, although no patients had grade 4 neuropathy.
“At 23 months of follow-up, 82% had either improvement or resolution of this peripheral neuropathy,” said Dr Kim.
There were 4 deaths in the brentuximab vedotin treatment arm, but they were attributed to disease-related complications, she said.