Abstract
According to survival results from a phase II trial of brentuximab vedotin, 34 patients with relapsed or refractory classic Hodgkin lymphoma had a complete response with this CD30-targeting antibody–drug conjugate; 13 remain in remission 5 years later.
According to survival results from a phase II trial of brentuximab vedotin (Adcetris; Seattle Genetics/Takeda), a sizeable fraction of patients with classic Hodgkin lymphoma (cHL) who had a complete response to this CD30-targeting antibody–drug conjugate are still in remission 5 years later.
“Practically speaking, if one stays in complete response for more than 5 years, the term ‘cure’ can be used,” says senior author Anas Younes, MD, chief of the lymphoma service at Memorial Sloan Kettering Cancer Center in New York, NY.
In 2011, based on data from this study, brentuximab vedotin received accelerated FDA approval to treat patients with relapsed or refractory cHL whose disease had progressed following an autologous stem cell transplant (auto-SCT, using one's own hematopoietic stem cells) or—if unsuitable for auto-SCT—at least two multichemotherapy regimens. The agency's nod stemmed from an objective response rate of 75% among 102 patients, including 34 complete responses.
Younes and colleagues now report that of these 34 complete responders, 13 (38%) remain in remission. Two additional patients who experienced partial disease regression were later recategorized as complete responders—after a follow-up allogeneic stem cell transplant (allo-SCT, requiring a matched donor)—and are also still in remission, bringing the total to 15.
“Given that historical outcomes are poor for cHL patients who relapse after auto-SCT, these results provide a new perspective on prognosis for this patient population,” the study investigators wrote. “The notion that allo-SCT is the only option for long-term disease control is challenged,” they added, because among the 13 original complete responders still in remission, only four had an allo-SCT after brentuximab vedotin.
“Allo-SCT is often associated with significant morbidity and mortality,” Younes explains. “In general, as more active agents become available and are incorporated in front-line and second-line regimens, the cure rate for cHL is expected to improve. Accordingly, the number of patients requiring allo-SCT will continue to decrease.”
For now, the combination of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) is a recognized first-line option for cHL, Younes adds. However, he and his colleagues are awaiting results from ECHELON-1, a randomized phase III study evaluating brentuximab vedotin plus AVD (no bleomycin) versus standard ABVD. “If the data are positive, it will change the standard of care,” he says.
Ajay Gopal, MD, a lymphoma specialist at Fred Hutchinson Cancer Research Center in Seattle, WA, concurs with Younes that “if ECHELON-1 is positive, it will likely alter the standard of care in North America, at least where ABVD is currently used.” Should this happen, “we'll need to refine who benefits most from adding brentuximab vedotin to AVD,” Gopal notes. “That said, there'll be some cost and toxicity savings if more patients do not require allo-SCT.”
Brentuximab vedotin is being evaluated in more than 30 clinical trials against multiple CD30-positive malignancies. It received full FDA approval for relapsed or refractory cHL in August 2015, and also has accelerated approval for patients with systemic anaplastic large cell lymphoma who have progressed on at least one multichemotherapy regimen. –Alissa Poh
