Phase II Trial of Nivolumab Plus Doxorubicin, Vinblastine, Dacarbazine as Frontline Therapy in Older Adults With Hodgkin Lymphoma
Pallawi Torka, Tatyana Feldman, Kerry J. Savage, Nivetha Ganesan, Esther Drill, Helen Hancock, Theresa Davey, Leslie Perez, Charisse Capadona, Sarima Subzwari, Natasha Galasso, Jin‐Shu Yang, Michelle Post, Alexander P. Boardman, Philip Caron, Kevin A. David, Zachary D. Epstein‐Peterson, Lorenzo Falchi, Paola Ghione, Paul A. Hamlin, Steven M. Horwitz, Andrew M. Intlekofer, W. Thomas Johnson, Anita Kumar, Jennifer Kimberly Lue, Ariela Noy, Colette Owens, M. Lia Palomba, Gilles Salles, Raphaël Steiner, Robert Stuver, Santosha A. Vardhana, Joachim Yahalom, Ahmet Doǧan, Andrew D. Zelenetz, Heiko Schöder, Alison J. Moskowitz
Abstract
PURPOSE: We conducted a phase I/II study evaluating nivolumab plus doxorubicin, vinblastine, dacarbazine (N-AVD) as frontline therapy for treatment-naïve older adults (OA) with classical Hodgkin lymphoma (cHL; ClinicalTrials.gov identifier: NCT03033914). METHODS: Patients age ≥60 years with newly diagnosed, any stage, cHL were treated with six cycles of AVD at standard doses plus nivolumab 240 mg intravenously once every 2 weeks (on days 1 and 15) of each cycle. A geriatric assessment was performed before therapy initiation. The primary end point was progression-free survival (PFS). RESULTS: Patient characteristics (N = 40) included median age of 66 years (range, 60-78 years) with 38% ≥70 years, 78% with stage III/IV disease, 68% with International Prognostic Score of ≥3, 82% dependent in ≥1 activities of daily living, 23% dependent in ≥1 instrumental activities of daily living, 50% with impaired timed up and go test, and 40% with polypharmacy. Among 37 response-evaluable patients, the median follow-up was 49 months and 3-year PFS and overall survival (OS) were 79% and 97%, respectively. Overall, 50% patients experienced grade 3/4 treatment-related adverse events (TRAEs), including febrile neutropenia in 8%. Four (10%) patients stopped therapy due to TRAEs. There was no correlation between baseline geriatric impairments and survival outcomes or toxicities. Positron emission tomography-2 was not predictive of PFS or OS. CONCLUSION: N-AVD is a highly effective and well-tolerated frontline regimen in OA with cHL across a wide range of geriatric impairments.