Brentuximab vedotin shows promise in Hodgkin lymphoma, concerns remain
ATLANTA — Brentuximab vedotin reduced the number of patients with Hodgkin lymphoma who required subsequent treatment, according to results of the phase 3 ECHELON-1 trial presented at the ASH Annual Meeting and Exposition.
“Some patients with Hodgkin lymphoma are young and [physicians] have to think ahead at what will happen 10, 20, and 30 years after treatment,” Steven I. Park, MD, chief of the division of hematology and oncology and director of investigational therapeutics in hematologic malignancies at the Levine Cancer Institute, told HemOnc Today. “We’ve seen a lot of long-term toxicities associated with chemotherapy. So, if you could reduce the number of patients who require subsequent treatment, I think it certainly is a big advantage.”
Standard chemotherapy is effective for approximately 75% of patients, but the remaining subset will likely progress and require additional treatment, according to Stephen M. Ansell, MD, PhD, chair of the lymphoma group at Mayo Clinic in Rochester, Minnesota, and HemOnc Today Editorial Board member.
“The reason that folks were enthusiastic about the results, or potential results, was that response rates were high, and the problems with bleomycin lung toxicities were not an issue,” Ansell told HemOnc Today.
An anti-CD30 antibody-drug conjugate, brentuximab vedotin (Adcetris, Seattle Genetics) in combination with doxorubicin, vinblastine and dacarbazine conferred superior modified PFS compared with standard chemotherapy among patients with high-risk Hodgkin lymphoma.
“Brentuximab vedotin has been very effective in [the] second- and third-line, and so that was now combined for front-line treatment,” Ansell said. “One of the problems in the initial studies was with bleomycin-related lung toxicity when you combined the two. So, dropping the bleomycin and using brentuximab vedotin instead, so the ABVD combination was what was moved forward into a randomized comparison with AVD.”
Ansell noted a trend toward benefit with brentuximab vedotin, but no significant survival advantage. Additionally, brentuximab vedotin is an expensive treatment option.
“It’s going to be very interesting to see how the community embraces the 5% benefit for quite substantial cost,” he said. “I guess the challenge has been, in the past, with more intensive chemotherapy, we’ve kind of taken the view that we don’t necessarily have to treat everybody because we can come back with transplantation and salvage people who progress with lesser therapy.”
The question, according to Ansell, is whether everyone should receive the combination or whether it is more beneficial to find a subset of patients who benefit the greatest from treatment.
“Whether it’s going to be standard-of-care for everyone is a little hard to tell at this point,” he said.
Park agreed that further analysis is needed to determine whether the approach will be practice-changing.
“We really need to look at the details,” he said. “The fact that it has not translated to an overall survival benefit ... [is] certainly somewhat concerning. And, we have to wait until the FDA makes the decision whether the use of brentuximab vedotin will be expanded to the front-line setting.”
Park also highlighted the potential cost of the therapy.
“As a physician, that’s the last thing we think about, but still we have to be cost sensitive because we have limited resources,” he said. “We have to take all those things into account, before we change our practice. Because, once we do that, it’s going to be a big change.”
He did acknowledge that it is not as simple as a cost analysis between replacing bleomycin with brentuximab vedotin. Although an inexpensive drug would be replaced with a novel, and more expensive drug, he said, it goes beyond comparing ABVD and brentuximab vedotin with AVD.
“We also have to take into consideration all the subsequent treatment, because it incurs cost with additional salvage chemotherapy, radiation and stem cell transplant, as well as long-term complications associated with them,” he said. “Some patients develop coronary artery disease, heart failure, marrow failure and secondary malignancies. So, it’s not going to be straightforward.”
Because the study met its primary endpoint and significantly fewer patients received subsequent treatment, the results are promising, Park said. However, there is a slight hesitation with the use of a modified PFS.
“The fact that we’re just dealing with the kind of new primary endpoint for us to decide our standard of care, in a way, it’s unknown territory for us to change our practice based on the somewhat unfamiliar primary endpoint with modified PFS,” he said. – by Ryan McDonald
Connors JM, et al. Abstract 6. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta.
Disclosures: Ansell reports that his institution receives research funding from Takeda. Park reports research funding from Bristol Myers-Squibb and Seattle Genetics.