Stephen M. Ansell, PhD, MD, on Hodgkin Lymphoma: An Updated Analysis on First-Line Brentuximab Vedotin Plus Chemotherapy
2022 ASCO Annual Meeting
Stephen M. Ansell, PhD, MD, of Mayo Clinic, discusses updated data from the ECHELON-1 trial, which showed that, when administered to patients with stage III or IV classical Hodgkin lymphoma, the combination of brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) vs doxorubicin, bleomycin, vinblastine, and dacarbazine resulted in a 41% reduction in the risk of death. These outcomes, says Dr. Ansell, confirm A+AVD as a preferred option for previously untreated disease (Abstract 7503).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Hodgkin lymphoma is a disease that commonly affects younger patients, but there is also a peak of patients in the older age group that have this disease. And it's proven to be one of the success stories in treatment of patients with cancer. Many patients with Hodgkin lymphoma have a very successful outcome with combination chemotherapy. ABVD chemotherapy has been the standard for decades and has actually been quite difficult to beat, particularly when one looks at overall survival. In the past, strategies have looked at ways to decrease toxicity by leaving out drugs that can cause lung toxicity, such as bleomycin. Other strategies have looked at intensifying therapy, treatments such as escalated BEACOPP. And these have shown that it may improve outcomes, particularly as far as progression-free survival is concerned, but none of these have really been able to impact the overall survival of patients. And the feeling has generally been that if you can salvage people with subsequent treatments, using high dose therapy and stem cell transplantation, you can actually result in a similar outcome, as far as overall survival is concerned. So, echelon one trial, the trial that was reported at this meeting, compared the use of a new targeted novel agent, as many people are aware, Brentuximab vedotin, it's a CD 30 antibody drug conjugate, in combination with AVD chemotherapy, against that standard, the ABVD chemotherapy. And just over 1300 patients were randomized in a one to one fashion. And the outcomes of those two cohorts of patients, treated for six cycles of therapy, were compared over time. Now, this data has been reported in a number of different time points. Initially, what was called the modified progression-free survival was reported, which showed an advantage to the Brentuximab AVD arm. Subsequently, regular progression-free survival showed a significant improvement, when compared to the standard. But the data presented now showed a 41% decrease in the likelihood of death from Hodgkin lymphoma, with the treatment with Brentuximab vedotin plus AVD chemotherapy. So, I think, quite frankly, this is a significant advance and moving the field forward. A few things that were very interesting about the study, when we actually looked at causes of death, there were more people passing away from Hodgkin lymphoma in the ABVD arm and fewer in the Brentuximab vedotin plus AVD arm. Now obviously, that would be expected, but there were fewer second malignancies, interestingly, in the Brentuximab vedotin AVD chemotherapy. And of particular note was, there were fewer other lymphomas that developed, suggesting that the Brentuximab vedotin may actually target a stem cell, or an earlier precursor cell, preventing those second malignancies. Additional data that looked at other toxicities that one is concerned about; Pregnancies, persistence of peripheral neuropathy, really were quite favorable showing that Brentuximab vedotin AVD chemotherapy is well tolerated and can be administered, and some of the toxicity seen actually subsequently resolve. So, when you take that all together and you say, "What does this data really show?" I think it shows that Brentuximab vedotin AVD chemotherapy, in advanced stage classical Hodgkin lymphoma patients, is a therapy with a better outcome than ABVD chemotherapy, and really now is the preferred frontline treatment for patients with this disease. I think the other thing that really is notable about this, we always believe that you could always turn around and salvage people subsequently with a subsequent strategy and treatment. This would suggest that what you do the first time actually impacts people overall, because when additional subsequent therapy was compared between the two arms, there was no real significant difference. So, taken together, that data would really say that the use of Brentuximab vedotin in combination with chemotherapy improves the outcomes of patients overall, and is now the preferred treatment for advanced stage patients.
Erika Hamilton, MD, of Sarah Cannon Research Institute at Tennessee Oncology, discusses phase III data from the DESTINY-Breast03 study, which reinforced the consistent safety profile of fam-trastuzumab deruxtecan-nxki (T-DXd) vs ado-trastuzumab emtansine (T-DM1) in patients with HER2-positive unresectable and/or metastatic breast cancer. The findings also support T-DXd’s risk benefit over that of T-DM1 (Abstract 1000).
Ruben A. Mesa, MD, of Mays Cancer Center at UT Health San Antonio MD Anderson Cancer Center, discusses new findings from the MOMENTUM study. This trial showed that in symptomatic and anemic patients with myelofibrosis, momelotinib was superior to danazol for symptom and spleen responses, as well as transfusion requirements (Abstract 7002).
Nabil F. Saba, MD, of Winship Cancer Institute of Emory University, discusses new data from a trial of pembrolizumab and cabozantinib in patients with recurrent metastatic head and neck squamous cell carcinoma. The study met its primary endpoint of overall response rate. The regimen was well tolerated and exhibited encouraging clinical activity in this patient population (Abstract 6008).
Michael J. Overman, MD, of The University of Texas MD Anderson Cancer Center, and Jeanne Tie, MBChB, MD, of Peter MacCallum Cancer Centre, discuss results from the DYNAMIC trial, in which a circulating tumor DNA (ctDNA)-guided approach reduced the use of adjuvant chemotherapy without compromising recurrence-free survival in patients with stage II colon cancer (Abstract LBA100).
Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, discusses long-term phase II findings of a trial evaluating crenolanib plus chemotherapy in newly diagnosed adults with FLT3-mutant acute myeloid leukemia. The study showed a composite complete remission rate of 86%. With a median follow-up of 45 months, median overall survival has not been reached. A phase III trial is ongoing (Abstract 7007).