Front-line Therapy with Brentuximab Vedotin Combined with ABVD or AVD in Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma (Abstract #798)
In this open-label, multicenter trial, cohorts of patients received an escalating dose of ADCETRIS (0.6 milligrams per kilogram (mg/kg), 0.9 mg/kg, 1.2 mg/kg) every two weeks concomitantly with ABVD or a dose of 1.2 mg/kg every two weeks concomitantly with AVD.
Fifty-one patients were enrolled in the phase I study and 47 were evaluable for response at trial completion. The 47 evaluable patients included 25 in the ADCETRIS plus AVD cohort and 22 in the ADCETRIS plus ABVD cohorts. All patients were previously untreated and 45 percent had Stage IV HL. The median age of patients across all cohorts of the trial was 33 years. Key findings, which were highlighted in an oral presentation by Dr. Stephen Ansell, Professor of Medicine, Division of Hematology, from the Mayo Clinic, included:
- Among the 25 evaluable patients in the ADCETRIS plus AVD cohort, 24 patients (96 percent) who completed front-line therapy on study achieved a complete remission and one patient (four percent) experienced disease progression.
- Among the 22 evaluable patients in the ADCETRIS plus ABVD cohorts, 21 patients (95 percent) who completed front-line therapy on study achieved a complete remission. One patient was not evaluable for response due to adverse events.
- Of the 48 evaluable patients in both study arms, 24 out of 26 (92 percent) in the AVD cohort and 22 out of 22 (100 percent) in the ABVD cohorts had negative interim PET scans after Cycle 2 as assessed by central review.
- No dose-limiting toxicity was observed at the maximum planned dose of ADCETRIS (1.2 mg/kg every two weeks).
- The most common adverse events noted in the ABVD and AVD cohorts, respectively, were nausea (72 percent, 85 percent), neutropenia (80 percent, 77 percent), peripheral sensory neuropathy (72 percent, 73 percent), vomiting (60 percent, 42 percent) and fatigue (44 percent, 50 percent).
- Grade 3 or higher adverse events occurring in more than one patient overall noted in the ABVD and AVD cohorts, respectively, were neutropenia (80 percent, 77 percent), anemia (20 percent, 12 percent), febrile neutropenia (20 percent, 8 percent) and pulmonary toxicity (24 percent, 0 percent). One patient experienced a Grade 3 peripheral neuropathy event.
- As previously reported in the interim analysis of this study, pulmonary toxicity was seen in the ADCETRIS plus ABVD cohorts, resulting in a contraindication for the concomitant administration of ADCETRIS and bleomycin. No pulmonary toxicity was observed in the ADCETRIS plus AVD cohort. In the ADCETRIS plus ABVD cohorts, 11 out of 25 patients (44 percent) had a pulmonary toxicity event, and events were resolved in nine of 11 patients (82 percent).
“For decades researchers have strived to improve our front-line HL treatment strategy by enhancing the activity of traditional chemotherapy regimens while reducing the significant toxicities and long-term side effects of such regimens,” said Stephen Ansell, M.D., Ph.D., Professor of Medicine, Division of Hematology, Mayo Clinic. “There is a significant need to identify better treatment options for patients in the front-line setting. With a complete response rate of 96 percent and a manageable safety profile, data from this trial support further evaluation of ADCETRIS administered concomitantly with AVD in previously untreated HL patients to potentially improve the current standard of care.”