Primary prophylaxis with G-CSF may improve outcomes in patients with newly diagnosed stage III/IV Hodgkin lymphoma treated with brentuximab vedotin plus chemotherapy

Abstract

We investigate the impact of granulocyte-colony stimulating factor (G-CSF) primary prophylaxis (G-PP, N = 83) versus no G-PP (N = 579) on safety and efficacy of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) in the ECHELON-1 study of previously untreated stage III/IV classical Hodgkin lymphoma. G-PP was associated with lower incidence of ≥ grade 3 neutropenia (29% versus 70%) and febrile neutropenia (11% versus 21%). Fewer dose delays (35% versus 49%), reductions (20% versus 26%), and hospitalizations (29% versus 38%) were observed. Seven neutropenia-associated deaths occurred in the A + AVD arm; none received G-PP. A + AVD with G-PP was associated with decreased risk of a modified progression-free survival event by 26% compared with A + AVD alone (95% CI: 0.40–1.37). G-PP reduced the rate and severity of adverse events, including febrile neutropenia, reduced treatment delays, dose reductions, and discontinuations, and may thus improve efficacy outcomes. These data support G-PP for all patients treated with A + AVD.

Keywords:

• Hodgkin lymphoma
• brentuximab vedotin
• frontline therapy
• growth factor
• primary prophylaxis

Acknowledgements

The authors wish to acknowledge Michael Harrison, PharmD, and Heather Brignull of Seattle Genetics, Inc. for assistance in manuscript preparation. DJ, GC, JW, PZ, AGrigg, AS, AI, TK, SA, LS, VB, AY, JC, AFT, and AGallamini were study investigators. KF and RL performed data analyses for the paper. All authors critically reviewed the data and manuscript and gave approval of the final draft.

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Disclosure statement

DS reports advisory board membership and consulting with Seattle Genetics and personal fees from Takeda. GC reports consulting for Bristol-Myers Squibb, Celleron, Gilead, MSD, Pfizer, Roche, and Takeda, honoraria from Bristol-Myers Squibb, Celleron, Gilead, MSD, Pfizer, Roche, and Takeda, research funding from Amgen, Celgene, Celleron, MSD, and speaker’s bureau fees and travel expenses from Roche and Takeda. JW reports advisory board memberships and consulting with Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Gilead, Incyte, Janssen-Cilag, Novartis, Takeda, Servier, and Roche, honoraria from Abbvie, Amgen, Celgene, Gilead, Janssen-Cilag, Roche, Servier, and Takeda, research funding from GlaxoSmithKline, Janssen-Cilag, Novartis, Roche, and Takeda, and travel expenses from Roche. PZ reports advisory board membership with Bristol-Myers Squibb, Celgene, Celltron, Eusapharma, Gilead, Immune Design, Janssen, Kyowa Kirin, MSD, Portola, Roche, Sandoz, Servier, and Verastem, consulting with Eusapharma, MSD, Sanofi, and Verastem, and serving with the speaker’s bureau at Bristol-Myers Squibb, Celgene, Celltron, Eusapharma, Gilead, Immune Design, Janssen, Kyowa Kirin, MSD, Portola, Roche, Servier, and Verastem. AGrigg reports advisory board membership and honoraria with Bristol-Myers Squibb, Gilead, Merck, Roche, and Takeda, consulting with Merck and Takeda, research funding from Seattle Genetics and Takeda, and travel expenses from Amgen. AS reports personal fees, research funding, honoraria, consulting, and speaker’s bureau with Takeda, consulting with Bristol-Myers Squibb, and personal fees from Sanofi. TK reports research funding from AstraZeneca-KHIDI. LS reports advisory board membership with Kyowa Kirin, MSD, and Takeda, speaker fees from Takeda, conference expenses from MSD, and research funding from Varian and ViewRay. VB reports research funding from MSD, Roche, Seattle Genetics, and Takeda. AY reports honoraria from Abbvie, Curis, Epizyme, Janssen, Merck, Roche, and Takeda, and research funding from Bristol-Myers Squibb, Curis, Janssen, Merck, Syndax, and Roche, and consulting with Epizyme, Biopath, Xynomics, Roche, Celgene, and HCM. JC reports research funding from NanoString Technologies, Seattle Genetics, and Takeda. AFT and KF are employees of and have equity ownership in Seattle Genetics. IP and RL are employees of and have equity ownership in Millennium Pharmaceuticals. AGautam was an employee of Millennium Pharmaceuticals at the time this work was completed. AGallamini reports honoraria from Takeda. AI and SA had no conflicts to report.

Additional information

Funding

This work was supported by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, and Seattle Genetics, Inc.