BMT Societies Issue Recommendations on Posttransplant Maintenance in HL/NHL
The American Society for Blood and Marrow Transplantation (ASBMT), Center for International Blood and Marrow Transplant Research (CIBMTR), and European Society for Blood and Marrow Transplantation (EBMT) have released consensus recommendations on the use of maintenance therapies after autologous transplantation for patients with Hodgkin (HL) or non-Hodgkin lymphoma (NHL).1
Use of maintenance therapy as a therapeutic strategy in posttransplant patients with HL and NHL is increasing in frequency, according to panel member Mehdi Hamadani, MD, of CIBMTR and Medical College of Wisconsin in Milwaukee. This joint panel was tasked with reviewing available data from clinical trials and summarizing evidence about the contemporary use of maintenance therapy in these patients to help guide therapy in a rapidly advancing field.
“Clinical trials evaluating maintenance treatments in lymphoma patients undergoing autologous transplantation cannot keep pace with the speed of drug development; which effectively means, by the time these trials are published the results are no longer applicable to modern patient population[s],” Dr Hamadani told Cancer Therapy Advisor.
For example, the large AETHERA clinical trial of brentuximab vedotin consolidation after autologous transplant in high-risk patients with HL showed that patients derived a disease-free survival benefit from that therapy.2 However, 1 of the main eligibility criteria for that trial was that patients could not have had prior exposure to brentuximab vedotin.
“The problem is that in 2018, brentuximab got approval for frontline therapy in HL and is also now commonly used in second-line therapy,” Dr Hamadani said. “The population that the AETHERA trial used is becoming less relevant in the real world and we have no trial data available on how to handle those patients.”
To issue its recommendations, the panel used the RAND-modified Delphi method, which generates consensus statements where at least 75% of a panel vote in favor of a recommendation. The panel issued 22 consensus recommendations. Several grade A recommendations, indicating good research-based evidence to support the recommendation, are discussed below.
The first consensus statement for HL was use of post-autologous hematopoietic stem cell transplantation (HCT) consolidation/maintenance with brentuximab vedotin for 16 cycles in brentuximab vedotin-naive classic HL with at least 1 or more high-risk features as defined by the AETHERA study.
A second grade A recommendation was rituximab maintenance therapy in patients with mantle cell lymphoma undergoing auto-HCT after first-line therapy. In these patients, a randomized trial has shown improved progression-free and overall survival with this maintenance regimen compared with observation alone.3
Rituximab maintenance was also recommended in rituximab-naive patients with follicular lymphoma. This recommendation was based primarily on data from the EBMT study,4 which showed that rituximab maintenance after transplant was safe and significantly prolonged progression-free (but not overall) survival.
“However, the panel acknowledges that rituximab-naive status at the time of auto-HCT in patients with FL in the current era would be rare, thus limiting the clinical impact of this statement,” the panelists wrote.
According to Henry Chi Hang Fung, MD, FACP, director of the Fox Chase-Temple University Hospital Bone Marrow Transplant Program in Philadelphia, Pennsylvania, these recommendations do not necessarily offer up any new data, but instead represent the opinion of bone marrow transplant experts.
“These are all based on studies that have already been published, some quite some time ago,” Dr Fung noted. “Because these are from multiple transplant societies, the target audience is definitely transplant doctors, who are highly specialized.”
“It is good to get everyone on the same page with recommendations like these, where there is consensus, and of equal importance are the areas where there is no consensus, like in DLBCL [diffuse large B-cell lymphoma],” Dr Fung said.
Dr Fung was referring to a final grade A consensus statement recommending against post-transplant maintenance therapy in patients with DLBCL.
According to Dr Hamadani, in patients with DLBCL, some clinicians may give maintenance therapy off-label, but there is a lack of evidence base for this.
“Maintenance therapies, even with older drugs like rituximab, are not free from side effects and are expensive,” Dr Hamadani said. “We reviewed all trials looking at rituximab after transplant in DLBCL and the studies were negative. They don’t show any survival benefit.”
Ongoing clinical trials looking at target therapies in DLBCL may change this recommendation in the future, but clinical trial data are not yet mature.
