Brentuximab vedotin, an antibody-drug conjugate that targets CD30-positive cells, was the focus of much attention at the 56th ASH Annual Meeting. Two studies highlighted the progress that is being made in the care of hard-to-treat Hodgkin lymphoma patients.
In the first study, Craig Moskowitz, MD, from the Memorial Sloan Kettering Cance Center in New York, described unprecedented results from the large AETHERA trial. This phase III, randomized, double-blind, placebo-controlled, multicenter trial investigated aimed to assess whether early treatment with brentuximab vedotin following autologous stem cell transplantation (ASCT) could prevent progression in patients with a history of relapsed/refractory Hodgkin lymphoma.
“Approximately half of the patients who undergo an ASCT will relapse, demonstrating a significant need to identify regimens that improve patient outcomes,” noted Dr. Moskowitz. In 2011, the U.S. Food and Drug Administration approved brentuximab vedotin for the treatment of patients with Hodgkin lymphoma after failure of ASCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates. Results from the AETHERA study lay the groundwork for further drug approvals.
A total of 329 patients at risk of post-ASCT disease progression were randomized to receive either brentuximab vedotin or placebo.
After a median follow-up of two years, patients receiving brentuximab vedotin had a significant increase in progression-free survival (PFS) per centralized, independent review compared to placebo (median of 43 months vs. 24 months, respectively; hazard ratio [HR] = 0.57; 95% CI 0.40–0.81; p=0.001).
The two-year PFS rate as assessed by the investigator was also significantly improved (65% for brentuximab vedotin vs. 45% for placebo; HR=0.50; 95% CI 0.36–0.70).
These are meaningful data, Dr. Moskowitz commented, because very few patients in this study population experience progression beyond two years.
The most common adverse events related to brentuximab vedotin treatment included peripheral sensory neuropathy (56%), upper neutropenia (35%), and upper respiratory tract infection (26%). Two deaths within 40 days of brentuximab vedotin dosing were reported.
Commenting on the findings during a press conference at the annual meeting, Brad Kahl, MD, associate professor of medicine at the University of Wisconsin School of Medicine and Public Health in Madison, called the AETHERA study’s results “practice-changing.” “This trial showed very convincingly that the application of brentuximab vedotin makes relapse far less likely for [high-risk] patients, and could represent a new standard of care for this patient population,” he said.
In the second study, Robert Chen, MD, from the City of Hope National Medical Center in Duarte, California, presented preliminary results from a prospective, multicenter, phase 2 trial, indicating brentuximab vedotin may be an efficacious first-line salvage therapy in patients with Hodgkin lymphoma after failed induction chemotherapy and prior to ASCT.
Of the 37 patients enrolled in the study, 36 were evaluable for response. Results showed an overall response rate of 69 percent, including a complete response rate of 36 percent. Furthermore, 89 percent of patients were able to proceed to ASCT. Fifty-two percent of these patients required no additional chemotherapy.
The problem with standard first-line salvage regimens is that they are associated with significant toxicities, Dr. Chen explained. Treatment with brentuximab vedotin, however, was well tolerated, with the most common (>25%) treatment-related adverse events including peripheral sensory neuropathy, aspartate aminotransferase elevation, alanine aminotransferase elevation, rash, fatigue, and generalized muscle weakness.
“Our findings show that one can effectively bridge a patient with relapsed/refractory Hodgkin lymphoma to ASCT with brentuximab vedotin alone,” Dr. Chen said. “Brentuximab vedotin has the same efficacy as [standard first-line salvage regimens] prior to ASCT and does not hinder stem cell collection or stem cell engraftment.”
- Moskowitz CH, Nadamanee A, Masszi T, et al. “The AETHERA trial: results of a randomized, double-blind, placebo-controlled phase 3 study of brentuximab vedotin in the treatment of patients at risk of progression following autologous stem cell transplant for Hodgkin lymphoma.” Abstract #673. Presented at the American Society of Hematology Annual Meeting, December 8, 2014.
- Chen RW, Palmer J, Martin P, et al. “Results of a phase II trial of brentuximab vedotin as first line salvage therapy in relapsed/refractory HL prior to AHCT.” Abstract #501. Presented at the American Society of Hematology Annual Meeting, December 8, 2014.