Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Dec 26;7(24):7485-7493.
doi: 10.1182/bloodadvances.2023010700.

Impact of cumulative dose of brentuximab vedotin on outcomes of frontline therapy for advanced-stage Hodgkin lymphoma

Raphael E Steiner  1 , Steven R Hwang  2 , Arushi Khurana  2 , Thomas M Habermann  2 , Narendranath Epperla  3 , Kaitlin Annunzio  3 , Pamela Blair Allen  4 , Katelin Baird  4 , Darina Paulino  4 , Juan Pablo Alderuccio  5 , Izidore S Lossos  5 , Kevin David  6 , Andrew M Evens  6 , Karan Pandya  6 , Steven M Bair  7 , Manali Kamdar  7 , Sheeba Ba Aqeel  8 , Pallawi Torka  8 , Ryan Lynch  9 , Stephen Smith  9 , Lei Feng  10 , Mansoor Noorani  1 , Sairah Ahmed  1 , Ranjit Nair  1 , Francisco Vega  11 , Susan Wu  12 , Penny Fang  12 , Chelsea C Pinnix  12 , Jillian R Gunther  12 , Bouthaina S Dabaja  12 , Hun J Lee  1
Affiliations

Impact of cumulative dose of brentuximab vedotin on outcomes of frontline therapy for advanced-stage Hodgkin lymphoma

Raphael E Steiner et al. Blood Adv. .

Abstract

In the pivotal study ECHELON-1, brentuximab vedotin (BV), doxorubicin, vinblastine, and dacarbazine (A + AVD) demonstrated superior efficacy compared with bleomycin + AVD for the treatment of advanced-stage classic Hodgkin lymphoma (cHL). However, there are minimal available data regarding the frequency of dose reductions or omission of BV during curative therapy and the potential impact on patient outcomes. In a real-world analysis, we retrospectively reviewed the characteristics and outcomes of 179 patients with stage III or IV cHL treated with frontline A + AVD from January 2010 to April 2022. Treatment consisted of up to 1.2 mg/kg of BV and standard dose AVD IV on days 1 and 15 of each 28-day cycle for up to 6 cycles. At the time of treatment, the median patient age was 37 years, and a high-risk International Prognostic Score was observed in 46% of patients. Overall, 91% of patients received 6 cycles of AVD; 55% of patients did not receive the intended cumulative dose of BV (CDB); 28% of patients received two-thirds or less than the planned CDB. At a median follow-up time of 27.4 months (95% confidence interval [CI], 24.8-29), the median progression-free survival (PFS) was not reached, and the 12-month PFS was 90.3% (95% CI, 85.9-95.0). The impact of CDB on PFS was not significant (P = .15), nor was high CDB significantly associated with increased adverse events. In real-world experience, A + AVD is a highly effective treatment for patients with advanced-stage cHL, including for patients with prominent dose reductions of BV.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: R.E.S. has received research funding from Seagen, Bristol Myers Squibb (BMS), GlaxoSmithKline, and Rafael Pharmaceuticals. T.M.H. is a member of the data monitoring committee at Seagen, Tess Therapeutics, and Eli Lilly and Company; is a member of the scientific advisory board of MorpohSys, Incyte, BeiGene, and Loxo Oncology; and receives research support to the Lymphoma Epidemiology of Outcomes grant from Genentech, Sorrento, and BMS. N.E. has received research funding from BeiGene; is a member of the speaker’s bureau for Incyte and BeiGene; and receives honoraria from, consults for, and serves on the advisory boards of Merck, ADC Therapeutics, Lilly, and Novartis. J.P.A. is a member of the advisory boards of ADC Therapeutics and Genentech, and has received research support from ADC Therapeutics. I.S.L. participated in the advisory board of Adaptive Biotechnology and provided lecture at Kyowa Kirin Pharmaceutical Development Inc. A.M.E. is a member of the advisory board (research-related) for Seattle Genetics, Hutchmed, Incyte, Daiichi Sankyo, and Epizyme, and is a consultant (a member of the data and safety monitoring board) for Novartis, AbbVie, and Pharmacyclics. M.K. has received research support/funding from Novartis; provided consultancy for AbbVie, AstraZeneca, Celgene/BMS, Adaptive Biotechnologies, ADC Therapeutics, BeiGene, Genentech, ImpactBio, and Syncopation; served on the speaker’s bureau of Seagen; and was part of the data management committee at Celgene and Genentech. P.T. has received consultancy fees from TG Therapeutics, ADC Therapeutics, Genentech, Kura Oncology, Seagen, Eli Lilly and Company, and Genmab. R.L. has received research funding from TG Therapeutics, Incyte, Bayer, Cyteir, Genentech, Seagen, and Rapt, and provided consultancy for Cancer Study Group, Seagen, and Foresight Diagnostics. S.S. has received research funding from ADC Therapeutics, AstraZeneca, Ayala (spouse), Bayer, BeiGene, BMS (spouse), De Novo Biopharma, Enterome, Genentech, Ignyta (spouse), Incyte Corporation, Kymera Therapeutics, Merck Sharp and Dohme Corp, MorphoSys, Nanjing Pharmaceuticals Co, Ltd, Portola Pharmaceuticals, and Viracta Therapeutics, and provided consultancy for or was a member of the advisory board of ADC Therapeutics, AstraZeneca, BeiGene, Epizyme, Karyopharm, Kite Pharma, Incyte, Numab Therapeutics AG, AbbVie, Coherus Biosciences advisory board (spouse), and Genentech. S.A. has received research support to institution for clinical trials from Seattle Genetics, Merck, Xencor, Chimagen, and Tessa Therapeutics; has membership on Tessa Therapeutics and Chimagen scientific advisory committee; serves on the data safety monitoring board for Myeloid Therapeutics; and is a consultant for ADC Therapeutics, and KiteE/Gilead. R.N. is consultant for AbbVie and had speaker/preceptorship disclosure from Incyte. F.V. received research funding from CRISP Therapeutics, Allogene, and Geron Corporation, and received in the past 3 years, honoraria from i3Health, Elsevier, America Registry of Pathology, Congressionally Directed Medical Research Program, Society of Hematology Oncology, and the National Research Foundation of Singapore. C.C.P. has received research support from Merck. B.S.D. has received research funding from Seagen. H.J.L. has received research funding from Seagen, BMS, Takeda, Oncternal Therapeutics, and Celgene; receives travel, accommodation, and expenses from Oncternal Therapeutics; receives honoraria from Aptitude Health, Cancer Experts Now, Curio Science, and Century Therapeutics; and reports consulting for or an advisory role at BMS and Guidepoint Global. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
PFS based on CDB during A + AVD frontline therapy. (A) All patients, (B) patients aged <60 years, and (C) patients aged ≥60 years.
See this image and copyright information in PMC

References

    1. Ansell SM, Radford J, Connors JM, et al. Overall survival with brentuximab vedotin in stage III or IV Hodgkin’s lymphoma. N Engl J Med. 2022;387(4):310–320. - PubMed
    1. Connors JM, Jurczak W, Straus DJ, et al. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin’s lymphoma. N Engl J Med. 2018;378(4):331–344. - PMC - PubMed
    1. Straus DJ, Długosz-Danecka M, Connors JM, et al. Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomised, phase 3 trial. Lancet Haematol. 2021;8(6):e410–e421. - PubMed
    1. Chen R, Gopal AK, Smith SE, et al. Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2016;128(12):1562–1566. - PMC - PubMed
    1. Straus D, Collins G, Walewski J, et al. Primary prophylaxis with G-CSF may improve outcomes in patients with newly diagnosed stage III/IV Hodgkin lymphoma treated with brentuximab vedotin plus chemotherapy. Leuk Lymphoma. 2020;61(12):2931–2938. - PubMed

Publication types

MeSH terms