The United States Food and Drug Administration (FDA) recently approved brentuximab vedotin in combination with chemotherapy as a first-line treatment for people with advanced-stage classical Hodgkin lymphoma.
Also known as Adcetris, brentuximab vedotin is an antibody drug conjugate that targets the CD30 protein present on lymphoma cells and delivers a toxin designed to promote cancer cell death. The drug has been previously approved to treat systemic anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma that has returned after prior therapy.
The FDA’s approval follows the encouraging results of the phase III ECHELON-1 clinical trial, presented at the 2017 American Society of Hematology (ASH) Meeting and Exposition and published in the New England Journal of Medicine. The trial, which was open at Weill Cornell Medicine and NewYork-Presbyterian Hospital, compared standard therapy with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) versus adriamycin, vinblastine and dacarbazine plus brentuximab vedotin (A+AVD).
Of the 1,300+ enrolled patients, those receiving A+AVD were demonstrated to be 23 percent less likely to experience disease progression, a need for additional therapy, or death, as compared to the cohort receiving the standard of care therapy.
“ABVD has been the standard therapy for a couple decades because it works really well, but it’s great to have new treatments available for people with Hodgkin lymphoma,” said Peter Martin, Chief of the Lymphoma Program. “I’m proud that we were able to offer this treatment at Weill Cornell a long time ago through the ECHELON-1 trial. Like any treatment, the A+AVD combination may not be right for everyone and requires consideration of side effects, like infection risk and neuropathy. Decisions between patients and physicians regarding the best treatment should follow an open discussion of the evidence.”
The Oncology Times reported on results from a small prospective, Phase II open label study published in Blood, that found brentuximab vedotin may be of use for elderly Hodgkin lymphoma patients, who cannot tolerate harsher chemotherapy treatment options. From the 19 patients the objective response rate was 92% with 73% of patients achieving a complete response rate and 19% a partial remission rate. First author, Dr. Andres-Forero-Torres MD reported:
“We took patients who were older than 60 and not candidates for chemotherapy due to comorbidities or who did not want to receive chemotherapy, and we treated them with brentuximab vedotin as a single agent…We were able to show in this small but significant population of patients that older patients tolerated brentuximab vendotin very nicely. We found very high rates of response–almost everybody had a response, and a very good percentage had a complete remission.”
“The issue is that the standard therapies in elderly and frail patients do have significant toxicity, so trying to come up with something that has less toxicity, if it can also be effective, is valuable…Brentuximab vedotin has less toxicity against the lungs, which is an issue with bleomycin, and less in the way of low blood count which you have in standard chemotherapy. It also avoids the cardiac toxicity of standard treatment as well.
On December 9, 2014 I wrote a brief post describing preliminary results from a phase II study of brentuximab vedotin as second-line therapy for Hodgkin lymphoma. The investigator-initiated study was performed jointly at City of Hope and Weill Cornell Medical College, highlighting a new era of collaboration between researchers working to improve the outcomes of people with lymphoma. The results of that study have now been published in the peer-reviewed journal Biology of Blood and Marrow Transplantation.
The purpose of the study was to evaluate the efficacy of brentuximab vedotin as second-line therapy in Hodgkin lymphoma (i.e., the lymphoma was not cured by first-line chemotherapy). Of the 37 study participants, almost half were able to proceed to potentially curative stem cell transplantation with brentuximab vedotin alone; i.e., no chemotherapy. Interestingly, all of the 13 patients that achieved a complete response with brentuximab vedotin did so within just 2 cycles (3 weeks).
This study suggests that brentuximab vedotin is efficacious in the second-line, pre-transplant setting, and that some patients may be spared cytotoxic chemotherapy prior to transplant. Moreover, responses seem to occur quickly in those people most likely to benefit, and there appears to be little rationale for continuing the same dose of brentuximab vedotin beyond 2 cycles in patients that have not achieved a complete response. Despite the clear activity of brentuximab vedotin in this setting, we do not advocate its use outside the context of a clinical trial until additional studies and longer follow up has been reported. Future studies will focus on combining brentuximab vedotin with other targeted agents with the intention of improving outcomes even more.
For more information about brentuximab vedotin look to this blog for further updates. If you are interested in Hodgkin lymphoma related clinical trials please visit our clinical trials listings.