Radhakrishnan Ramchandren, MD
The North American subgroup analysis of the phase III ECHELON-1 trial revealed more than double the improvement seen with brentuximab vedotin (Adcetris) plus doxorubicin, vinblastine, and dacarbazine (A+AVD) compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) versus the primary study findings in patients with advanced Hodgkin lymphoma, explained lead author Radhakrishnan Ramchandren, MD.
The initial results of the global study indicated a 5.1% benefit with A+AVD in 2-year modified progression-free survival (mPFS) compared with ABVD. However, in an interview during the 2018 OncLive®
State of the Science Summit™ on Hematologic Malignancies, Ramchandren noted that benefit was not distributed globally. The subgroup analysis revealed an absolute difference of 10.6% in mPFS per independent review facility and an 11.7% difference in PFS per investigator review at 2 years.1
“It is unlikely to be a statistical anomaly,” said Ramchandren. “That being said, it is a subgroup analysis and must be evaluated prospectively to be confirmed. The difference is more than double what we saw globally and may suggest a benefit for A+AVD that is larger in the North American component as opposed to other parts of the world.”
In March 2018, the FDA approved the frontline combination of brentuximab vedotin and chemotherapy for adult patients with stage III/IV classical Hodgkin lymphoma based on the ECHELON-1 results.2
In the interview, Ramchandren, associate professor, Wayne State University School of Medicine, Karmanos Cancer Institute, gave an overview of the treatment landscape in Hodgkin and T-cell lymphoma before delving into the results of the North American subgroup analysis of the ECHELON-1 trial.
OncLive: Can you provide an overview of your lectures on Hodgkin lymphoma and T-cell lymphoma?
Hodgkin lymphoma is a disease that occurs in young individuals. It has been a landmark condition because we have historically had early success in treating it. However, this has come at the cost of toxicities—both acute and long-term—for patients who survive. There are patients who unfortunately don't respond to standard chemotherapy and radiation and relapse. For those patients, autologous stem cell transplant (ASCT) is an option. However, some of those patients can't achieve a remission and go to transplant or are unable to go to transplant for other reasons. For those individuals, expectations are very short in terms of lifespan and quality of life.
New drugs have been developed over the course of the last decade in Hodgkin lymphoma, which have been groundbreaking in terms of their mechanism of action and activity. They have been evaluated in earlier lines of therapy and in combination with chemotherapy. Most recently, the ECHELON-1 data incorporated A+AVD versus standard therapy with ABVD in advanced-stage disease.
A+AVD showed a benefit in mPFS. This is one of the first, if any, studies that incorporated a novel agent to a chemotherapy backbone in Hodgkin lymphoma and showed this benefit.
Secondarily, checkpoint inhibitors have shown significant activity in the relapsed setting. Now, multiple studies are also evaluating this in the frontline setting, so it's a very exciting time.
T-cell lymphoma is a relative rarity in the lymphoma world in comparison to B-cell lymphomas. Only about 10% to 15% of people who have lymphoma have T-cell lymphoma. They're largely broken down into 3 categories: cutaneous, systemic, and leukemic. Unfortunately, the outcomes for these patients are poorer than those with B-cell lymphoma.
Improvements in therapy have been somewhat sluggish. That being said, in the past decade, there have been great advances in understanding the biology of this disease. The incorporation of novel agents has become more common, particularly in the relapsed setting. There have been studies looking at incorporating these agents in the frontline setting as well. We are eagerly awaiting some of these results. In the past year, there have been approvals for novel drugs in the T-cell lymphoma world.
Why has immunotherapy shown more success in Hodgkin lymphoma as opposed to other hematologic malignancies?
If we understood the biology not only of Hodgkin lymphoma, but other tumors better, I would have a better answer for you. I will say there is something to be said for exceptions to the rule. Hodgkin lymphoma certainly seems to be an exception in its response rate. There is much we can learn about immune evasion and malignancy through Hodgkin lymphoma. This disease is unique in the particular microenvironment it espouses, and its ability for a malignant cell to coordinate its microenvironment and evolve over time.