First-Time Finding in Posttransplant Hodgkin Lymphoma

Roxanne Nelson

December 06, 2014

SAN FRANCISCO ― Maintenance therapy with brentuximab vedotin (Adcetris, Seattle Genetics, Inc) can extend progression-free survival in high-risk patients with Hodgkin lymphoma following transplantation, according to new data.

This is the first time a study has demonstrated that adding a maintenance therapy after transplant can improve outcomes.

At a median follow-up of 2 years, progression-free survival was 65% for patients who received brentuximab, compared with 45% in the placebo arm ― a 20% absolute improvement.

"This was sustained across all subgroups," said lead author Craig H. Moskowitz, MD, clinical director of the Division of Hematologic Oncology at Memorial Sloan Kettering Cancer Center in New York City.

Dr Craig H. Moskowitz

Speaking at a press briefing held here during the American Society of Hematology (ASH) 56th Annual Meeting, Dr Moskovitz noted that "once this study is published, and among patients who met the eligibility criteria to be on the study, in my opinion, this treatment could be standard of care."

High-dose chemotherapy plus autologous stem cell transplant (ASCT) has been the standard of care for patients with chemosensitive relapsed/refractory Hodgkin lymphoma for the past 2 decades. For about half of patients, this regimen is curative. But despite optimization of salvage chemotherapy, supportive care, and patient selection, the authors note that improvements in post-ASCT outcomes have plateaued. This phenomenon is most likely due to disease progression in patients with high-risk factors, and the majority of this group will progress following transplantation. Thus, they note, new therapies are needed for this group.

"We've been transplanting patients with Hodgkin lymphoma for almost 30 years, and unfortunately, progression-free survival has been fairly stable at 40% to 55%,” explained Dr Moskowitz. Brad Kahl, MD, moderator of the session, agreed that this is the first study to show a significant benefit in this population. "The big question is about the long-term use of brentuximab vedotin as maintenance therapy," he pointed out.

It is unknown at this time whether the patients who responded to the drug will eventually relapse or will be cured, said Dr Kahl, director of the University of Wisconsin Lymphoma Service and clinical research director for hematologic malignancies for the University of Wisconsin Carbone Cancer Center.

Patient Aspects Important

Brentuximab vedotin is an antibody-drug conjugate (ADC) composed of a CD30 monoclonal antibody conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E (MMAE).

The AETHERA trial was initiated to evaluate whether early treatment with brentuximab vedotin after ASCT can prevent progression in high-risk Hodgkin lymphoma patients.

This phase 3, randomized, multicenter study compared brentuximab vedotin with placebo in 327 patients at risk for posttransplant disease progression. All trial participants either had achieved remission or had stable, nonprogressing disease at time of transplant.

They were enrolled in one of three high-risk categories: refractory to frontline therapy (196 patients, 60%); relapse less than 12 months after frontline therapy (107 patients, 33%); and relapse 12 months or longer after frontline therapy with extranodal disease (26 patients, 8%).

All patients were required to have obtained a complete remission, partial remission, or to have stable disease after salvage therapy prior to ASCT.

After undergoing ASCT, the cohort received brentuximab vedotin 1.8 mg/kg q3wk and best supportive care or placebo and best supportive care for up to 16 cycles (approximately 12 months). Those with progressive disease discontinued study therapy and could request unblinding.

There were two aspects with regard to patient characteristics that were important, Dr Moskowitz pointed out.

"One is that almost of half of patients needed more than one salvage therapy to become chemosensitive disease to even be eligible for a transplant. In itself, patients who need more than one salvage regimen have about a 20% to 30% chance of actually being a long-term survivor.”

"Second," Dr Moskowitz continued, "probably the most important factor is patients who have primary refractory disease. About 60% of the patients did not achieve a remission with up-front chemotherapy."

The median age of patients was 32 years, and they were evenly divided with respect to sex. The median number of prior systemic therapies (frontline and salvage) was two (range, two to eight), and overall, 78% of the group had multiple risk factors for progression.

At the current time, overall survival is 88%.

Interim analysis of overall survival did not show a significant difference between treatment arms (P = .62). But that was not surprising, explained Dr Moskowitz. "Patients were allowed to cross over, so the likelihood of having an overall survival difference was not expected."

The main reasons for treatment discontinuation were disease progression (n = 93, 28%), adverse events (n = 61, 19%), patient decision (n = 15, 5%), and investigator decision (n = 1, <1%).

Of the 50 deaths, eight occurred prior to disease progression.

Adverse events of any grade that occurred in more than 15% of patients included peripheral sensory neuropathy (36%), upper respiratory tract infection (25%), neutropenia (24%), fatigue (21%), cough (19%), and pyrexia (17%).

Adverse events of grade 3 or higher that were observed in 10 or more patients were neutropenia (20%), peripheral sensory neuropathy (6%), thrombocytopenia (3%), and peripheral motor neuropathy (3%). In addition, 144 patients (44%) experienced treatment-emergent peripheral neuropathy.

Dr Moskowitz and several coauthors have reported financial relationships with industry.

American Society of Hematology (ASH) 56th Annual Meeting: Abstract 673. Presented December 8, 2014.

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