In a phase II study, the 34 evaluable patients with peripheral T-cell lymphomas who received brentuximab vedotin (Adcetris) had an overall response rate of 41%, including an overall response rate of 54% among the 13 patients with angioimmunoblastic T-cell lymphoma. The median progression-free survival at the time the study was reported in Blood was 6.7 months. Brentuximab vedotin was generally well tolerated.
“Based on the activity and safety observed in patients on this investigational phase 2 trial, single-agent brentuximab vedotin has the potential to be a therapeutic option in treating relapsed and refractory [peripheral T-cell lymphomas],” Steven M. Horowitz, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues concluded.
Study participants were enrolled at 13 sites in the United States and 1 in Canada. Eligibility criteria included histologically confirmed mature T-cell lymphoma with any detectable CD30 expression, the investigators explained. Patients with anaplastic large cell lymphoma, Sezary syndrome, and mycosis fungoides were excluded. The median age of patients was 64 years; 77% were male, and 71% were white. Most patients (77%) had stage III or IV disease, and 63% were refractory to most recent therapy.
Patients were treated with brentuximab vedotin, a CD30-directed antibody-drug conjugate, at 1.8 mg/ kg intravenously on day 1 of each 3-week cycle. “Patients who achieved at least stable disease … were eligible to receive continued brentuximab vedotin treatment until disease progression, unacceptable toxicity, or study closure. Patients who received at least one dose of brentuximab vedotin were followed for disease status and survival,” the investigators explained.
Among the 14 patients achieving an objective response, 8 had complete responses, including 5 patients with angioimmunoblastic T-cell lymphoma. At the time of the study report, the median duration of response for all patients was 7.6 months, with five responding patients remaining in follow-up and five on therapy.
“Safety data were generally consistent with the known profile of brentuximab vedotin,” the researchers reported. “The most frequently occurring ≥ Grade 3 events were neutropenia (14%), peripheral sensory neuropathy, and hyperkalemia (9% each).”
Serious adverse events occurred in four patients, including grade 3 pyrexi, rash, and pneumonia, and grade 5 acute respiratory distress syndrome. Three patients died within 30 days of receiving the last dose, one due to acute respiratory distress syndrome and two related to disease progression, and another patient died after 30 days with severe complications including sepsis unrelated to treatment.
“The response rates in this trial and the lack of correlation with CD30 expression suggest potentially broad activity of brentuximab vedotin among various subtypes of T-cell lymphomas,” the authors stated. They also pointed out that the overall response rate achieved was “comparable to that in similar populations studied with other recently approved agents,” such as pralatrexate (Folotyn) and romidepsin (Istodax).
“The results from the current phase 2 trial in [peripheral T-cell lymphomas] coupled with the ability to combine brentuximab vedotin with standard induction chemotherapy has led to the initiation of a phase 3, double-blinded randomized study,” the authors added. That study will compare brentuximab vedotin plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) vs CHP (CHOP minus vincristine) for untreated patients with CD30-expressing mature T-cell lymphomas.
The current study was registered at ClinicalTrials.gov with the identifier NCT01421667. ■
Horwitz SM, et al: Blood. March 20, 2014 (early release online).