Immune Checkpoint Inhibitors Further Refine Hodgkin Lymphoma Regimens

John M. Burke, MD

Hematologist and Medical Oncologist

Rocky Mountain Cancer Centers

Associate Chair

US Oncology Hematology

Research Program

Aurora, CO

Most hematologists and oncologists in practice today probably learned that the regimen most likely to cure Hodgkin lymphoma is the combination of doxorubicin, bleomycin, vinblastine, and dacarbazine, commonly referred to as ABVD. In the early 1990s ABVD demonstrated improved failure-free survival (but not overall survival) and lower toxicity compared with the older regimen of MOPP (mechlorethamine hydrochloride, vincristine sulfate [Oncovin], procarbazine hydrochloride, and prednisone).

In 2018 things changed when data from the ECHELON-1 trial (NCT01712490) showed that the replacement of bleomycin in the ABVD regimen with brentuximab vedotin (BV-AVD) demonstrated superior progression-free survival (PFS) in patients with advanced-stage Hodgkin lymphoma. Many experts considered BV-AVD to be one standard of care, along with ABVD, but not the only standard of care. However, since 2022, when updated ECHELON-1 results demonstrated that an overall survival difference had emerged between the 2 groups, BV-AVD became the preferred regimen for patients with advanced-stage Hodgkin lymphoma.

During the plenary session of the 2023 American Society of Clinical Oncology Annual Meeting, we learned that BV-AVD’s reign at the top may be short lived. SWOG S1826 (NCT03907488) compared BV-AVD with an investigational arm that replaced BV with nivolumab (Opdivo; N-AVD) in patients with advanced-stage Hodgkin lymphoma. Results of the second interim analysis showed the HR for PFS was 0.48 (P = .0005) in favor of the N-AVD arm. One-year PFS rates in the N-AVD and BV-AVD groups were 94% and 86%, respectively.

Paradoxically, I find these exciting results to be a little disappointing. As BV is clearly one of our better drugs for the disease, I cannot help wonder whether, by leaving it on the shelf, we will be delivering the best regimen for patients with the tools we have. Indeed, one clinical trial (NCT03646123) has already studied the combination of nivolumab, brentuximab vedotin, doxorubicin, and dacarbazine, and demonstrated promising results. Of course, without a randomized trial, we can only speculate whether that regimen would be superior to N-AVD.

But after decades of relatively little progress, against a cancer that, although not the most common, causes the loss of many years of life, we can only be thankful that we live in this era in which our treatment options for patients keep getting better and better.