Multicenter phase II study of sequential brentuximab vedotin and doxorubicin, vinblastine, and dacarbazine chemotherapy for older patients with untreated classical hodgkin lymphoma Journal Article


Authors: Evens, A. M.; Advani, R. H.; Helenowski, I. B.; Fanale, M.; Smith, S. M.; Jovanovic, B. D.; Bociek, G. R.; Klein, A. K.; Winter, J. N.; Gordon, L. I.; Hamlin, P. A.
Article Title: Multicenter phase II study of sequential brentuximab vedotin and doxorubicin, vinblastine, and dacarbazine chemotherapy for older patients with untreated classical hodgkin lymphoma
Abstract: Purpose To improve the curability of older patients with newly diagnosed Hodgkin lymphoma. Patients and Methods We conducted a multicenter phase II study that administered brentuximab vedotin (Bv) sequentially before and after standard doxorubicin, vinblastine, and dacarbazine (AVD) for untreated patients with Hodgkin lymphoma age 60 years or older. After two lead-in doses of single-agent Bv (1.8 mg/kg once every 3 weeks), patients received six cycles of AVD chemotherapy followed by four consolidative doses of Bv in responding patients. Results Patient characteristics included median age of 69 years (range, 60 to 88 years), 63% male,median Eastern Cooperative Oncology Group performance status 1, 81% stage III to IV disease, 60% International Prognostic Score 3 to 7, median Cumulative Illness Rating Scale-Geriatric comorbidity score of 7 (52% grade 3 to 4); and 12% had loss of instrumental activities of daily living at diagnosis. Thirty-seven (77%) of 48 patients completed six cycles of AVD, and 35 patients (73%) received at least one Bv consolidation. Overall response and complete remission rates after initial Bv lead-in dose were 18 (82%) of 22 and 8 (36%) of 22, respectively, and 40 (95%) of 42 and 34 (90%) of 42, respectively, after six cycles of AVD among 42 response-evaluable patients. Twenty (42%) of 48 patients experienced a grade 3 to 4 adverse event, most commonly neutropenia (44%), febrile neutropenia and pneumonia (8%), or diarrhea (6%); 33% had grade 2 peripheral neuropathy, which was reversible in amajority of patients. By intent-to-treat, the 2-year event-free survival, progression-free survival, and overall survival rates were 80%, 84%, and 93%, respectively. Furthermore, 2-year progression-free survival rates for patients with a Cumulative Illness Rating Scale-Geriatric comorbidity score of ≥ 10 versus <10 were 45% versus 100%, respectively (P <.001), and with baseline loss versus no loss of instrumental activities of daily living were 25% versus 94% (P <.001), respectively, the latter persisting on multivariable analyses. Conclusion Altogether, sequential Bv-AVD was well tolerated and was associated with robust outcomes. Furthermore, geriatric-based measures were strongly associated with patient survival. © 2018 by American Society of Clinical Oncology.
Journal Title: Journal of Clinical Oncology
Volume: 36
Issue: 30
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2018-10-20
Start Page: 3015
End Page: 3022
Language: English
DOI: 10.1200/jco.2018.79.0139
PROVIDER: scopus
PUBMED: 30179569
DOI/URL:
Notes: Conference Paper -- Export Date: 1 November 2018 -- Source: Scopus
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MSK Authors
  1. Paul Hamlin
    168 Hamlin