Optimizing First-Line Treatment Selection Across in Early- and Advanced-Stage Hodgkin Lymphoma

Clinical Summary:

• Catherine Diefenbach, MD, examines the evolving first-line treatment landscape for patients with classical Hodgkin lymphoma, comparing nivolumab-based immunotherapy, brentuximab vedotin-containing regimens, and established ABVD-based chemotherapy across early- and advanced-stage disease.
• The S1836 and HD21 trials support nivolumab plus AVD and BrECADD, respectively, as effective first-line options for advanced-stage Hodgkin lymphoma, while established ABVD-based regimens remain effective for early-stage disease given their favorable long-term outcomes. 
• These findings emphasize the importance of balancing progression-free survival, treatment-related toxicity, and financial burden when selecting first-line therapy, particularly as newer immunotherapy-based regimens expand treatment options for advanced-stage disease. 

Catherine Diefenbach, MD, NYU Langone Health and Perlmutter Cancer Center, New York, New York, discusses the evolving first-line treatment landscape for patients with classical Hodgkin lymphoma, including the integration of checkpoint inhibitors and brentuximab vedotin-based regimens. 

Dr Diefenbach reviews findings from the S1826 and HD21 trials supporting nivolumab plus AVD and BrECADD in advanced-stage Hodgkin lymphoma, highlighting differences in efficacy, toxicity, and treatment administration. She also discusses the continued role of response-adapted ABVD-based therapy in early-stage disease and the importance of avoiding unnecessary treatment intensification when selecting first-line regimens.

Transcript:

Hello, this is Dr Catherine Diefenbach talking to you from LL&M. I'm professor of medicine at NYU Langone School of Medicine and I work in the Perlmutter Cancer Center at NYU Langone. I'm very happy to talk to you from the LL&M conference. 

What I will be talking about this afternoon is the management of Hodgkin lymphoma in the first line. This is a very exciting time for Hodgkin lymphoma because we have a new drug, a checkpoint inhibitor called nivolumab, that has been approved in advanced stage disease in first frontline for my patients.

We have another study from the German Hodgkin-focused study group that looks at a regimen called BrECADD that also is an option for advanced stage frontline patients. This is on top of standard-of-care ABVD-based chemotherapy using a risk-adapted strategy to minimize bleomycin toxicity by treating with 2 cycles of ABVD, and then for PET-negative patients, dropping the bleomycin after 4 cycles of therapy. 

My talk focuses on whether all patients should be treated with checkpoint inhibitors in the frontline or only some. What I basically do is look at the data for both early- and advanced-stage. In advanced-stage disease, we have two trials, S1826 and HD21, which look at nivolumab and brentuximab vedotin, respectively. Nivolumab is a checkpoint inhibitor, brentuximab vedotin is an anti-CD30 antibody drug conjugate. 

In the NAVD study, patients were randomized to either nivolumab-AVD or ABVD, and for the full population, there was an improvement in progression-free survival at 3 years. There was no improvement in overall survival. The improvement was statistically significant, and the regimen was manageable. In the BrECADD data, patients were randomized to either escalated BEACOPP or BrECADD, which was a less toxic regimen than the escalated BEACOPP. Here we have 5-year data showing that the BrECADD was not only non-inferior to the escalated BEACOPP, but superior, and these patients had an excellent progression-free survival advantage. 

I outlined some advantages and disadvantages to both regimens in my talk. The NAVD regimen has less myelosuppression and hematologic toxicity, and is easier to give, has a slightly lower progression-free survival at 3 years than the BrECADD, which is more challenging to give, and has more immunologic toxicity. However, it has a superior progression-free survival at 5 years. The NAVD arm also has immunologic toxicity, which the BrECADD arm does not have.

I then talk about early-stage patients and I look at the studies in early-stage patients with 2 to 4 to 6 cycles of ABVD, +/- radiation, and go through the data for all of this and discuss some other smaller studies looking at the integration of nivolumab or brentuximab. 

What I conclude is that for early-stage patients, there are many options of ABVD-based regimens, either with or without radiation, that have been validated with long follow-up in randomized trials. While nivolumab and brentuximab are exciting, we don't need to over-treat 90% of patients to improve a progression-free survival of 5% when the overall survival difference is no different. I talk about the financial toxicity, which is substantial with the newer agents. 

With regard to early-stage patients, we should remain on an ABVD-based therapy until we have randomized clinical trial data to show us that we should adopt a new standard. Then for advanced-stage patients, we have really two strong options in addition to response-adapted ABVD therapy, and that includes NAVD following S1826 or BrECADD following HD21.