Highlights of ASCO: Hodgkin’s Lymphoma S1826 Study

By Dr. Luke Fletcher

Willamette Valley Cancer Institute & Research Center

 

Hodgkin’s lymphoma (HL) has had an exciting and interesting recent history with the introduction of brentuximab (BV) +AVD (Adriamycin, vinblastine, dacarbazine) frontline in the ECHELON-1 trial with both PFS and OS benefit over ABVD chemotherapy (1,2).  This paradigm is under challenge with the SWOG S1826 study, investigating Nivolumab (N) + AVD vs. BV  + AVD in stage 3 or 4 HL. Patients were randomized 1:1 to six cycles of N-AVD or BV-AVD (3). The primary endpoint was PFS, with secondary endpoints including patient-reported outcomes, safety, and overall survival.

 

976 patients were randomized 1:1 as above. At one year, PFS was improved in the N-AVD vs. BV-AVD (94% vs. 86%, p <0.0005).  There was more neutropenia in the N-AVD group but more growth factor use and bone pain in the BV-AVD group. Moreover, there was less discontinuation of N-AVD (11% vs. 22%) and much less neuropathy (29% vs. 55%), indicating better overall tolerability.

 

There is more data to come, such as a full assessment of PFS to ensure durability and a complete evaluation of secondary endpoints, such as overall survival, among other things. Still, based on this data, it is widely expected that Nivolumab +AVD will become the new standard of care for advanced classic Hodgkin’s lymphoma once approved.

 

Key Points:

• Nivolumab +AVD improved PFS in comparison to Brentuximab + AVD, 94% vs. 86% at one year
• Safety profile seems to favor Nivolumab + AVD, with more patients staying on therapy with less neuropathy
• Overall survival data is still to be anticipated from study

 

References:

1) Connors JM, Jurczak W, Straus DJ, et al. ECHELON-1 Study Group. Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin’s Lymphoma. N Engl J Med. 2018 Jan 25;378(4):331-344. doi: 10.1056/NEJMoa1708984. Epub 2017 Dec 10. Erratum in: N Engl J Med. 2018 Mar 1;378(9):878. PMID: 29224502; PMCID: PMC5819601.

2) Ansell SM, Radford J, Connors JM, Długosz-Danecka M, Kim WS, Gallamini A, Ramchandren R, Friedberg JW, Advani R, Hutchings M, Evens AM, Smolewski P, Savage KJ, Bartlett NL, Eom HS, Abramson JS, Dong C, Campana F, Fenton K, Puhlmann M, Straus DJ; ECHELON-1 Study Group. Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin’s Lymphoma. N Engl J Med. 2022 Jul 28;387(4):310-320. doi: 10.1056/NEJMoa2206125. Epub 2022 Jul 13. PMID: 35830649.

3) Herrera AF, LeBlanc ML, Castellino SM, et al. SWOG S1826, a randomized study of nivolumab(N)-AVD versus brentuximab vedotin(BV)-AVD in advanced stage (AS) classic Hodgkin lymphoma (HL). J Clin Oncol. 2023;41(suppl 17):LBA4. doi:10.1200/JCO.2023.41.16_suppl.LBA4