Zanubrutinib, obinutuzumab, and venetoclax for first-line treatment of mantle cell lymphoma with a <i>TP53</i> mutation
Abstract
Abstract TP53-mutant mantle cell lymphoma (MCL) is associated with poor survival outcomes with standard chemoimmunotherapy. We conducted a multicenter, phase 2 study of zanubrutinib, obinutuzumab, and venetoclax (BOVen) in untreated patients with MCL with a TP53 mutation. Patients initially received 160 mg zanubrutinib twice daily and obinutuzumab. Obinutuzumab at a dose of 1000 mg was given on cycle 1 day 1, 8, and 15, and on day 1 of cycles 2 to 8. After 2 cycles, venetoclax was added with weekly dose ramp-up to 400 mg daily. After 24 cycles, if patients were in complete remission with undetectable minimal residual disease (uMRD) using an immunosequencing assay, treatment was discontinued. The primary end point was met if ≥11 patients were progression free at 2 years. The study included 25 patients with untreated MCL with a TP53 mutation. The best overall response rate was 96% (24/25) and the complete response rate was 88% (22/25). Frequency of uMRD at a sensitivity level of 1 × 10–5 and uMRD at a sensitivity level of 1 × 10–6 at cycle 13 was 95% (18/19) and 84% (16/19), respectively. With a median follow-up of 28.2 months, the 2-year progression-free, disease-specific, and overall survival were 72%, 91%, and 76%, respectively. Common side effects were generally low grade and included diarrhea (64%), neutropenia (32%), and infusion-related reactions (24%). BOVen was well tolerated and met its primary efficacy end point in TP53-mutant MCL. These data support its use and ongoing evaluation. This trial was registered at www.ClinicalTrials.gov as #NCT03824483.
Article Details
Authors (28)
Anita Kumar
1memorial Sloan Kettering, NYC, United States
Jacob Soumerai
12Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, United States
Jeremy S. Abramson
1Department of Medical Oncology, Massachusetts General Hospital, Boston, MA
Jeffrey A. Barnes
5Hematology and Oncology Division, Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Philip Caron
1memorial Sloan Kettering, NYC, United States
Shalini Chhabra
1Memorial Sloan Kettering Cancer Center, Lymphoma Division, New York, United States
Maria Chabowska
1Memorial Sloan Kettering Cancer Center, Lymphoma Division, New York, United States
Ahmet Dogan
Hematopathology Service, Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York
Lorenzo Falchi
Memorial Sloan Kettering Cancer Center, New York
Clare Grieve
1Memorial Sloan-Kettering Cancer Center, Medicine, Lymphoma Service, NEW YORK, United States
J. Erika Haydu
Department of Medicine, Massachusetts General Hospital, Boston
Patrick Connor Johnson
2Massachusetts General Hospital Cancer Center, Center for Lymphoma, Boston, United States
Ashlee Joseph
1Memorial Sloan Kettering Cancer Center, Lymphoma Division, New York, United States
Hailey E. Kelly
2Center for Lymphoma, Massachusetts General Hospital Cancer Center, Boston, MA
Alyssa Labarre
1Memorial Sloan Kettering Cancer Center, Lymphoma Division, New York, United States
Jennifer Kimberly Lue
1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Rosalba Martignetti
2Massachusetts General Hospital Cancer Center, Center for Lymphoma, Boston, United States
Joanna Mi
1Memorial Sloan Kettering Cancer Center, Lymphoma Division, New York, United States
Alison Moskowitz
1memorial Sloan Kettering, NYC, United States
Colette Owens
1Memorial Sloan Kettering Cancer Center, New York, United States
Sean Plummer
2Massachusetts General Hospital Cancer Center, Center for Lymphoma, Boston, United States
Madeline Puccio
2Massachusetts General Hospital Cancer Center, Center for Lymphoma, Boston, United States
Gilles Salles
41Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY
Venkatraman Seshan
1Memorial Sloan-Kettering Cancer Center, Medicine, Lymphoma Service, NEW YORK, United States
Elizabeth Simkins
2Massachusetts General Hospital Cancer Center, Center for Lymphoma, Boston, United States
Natalie Slupe
1Memorial Sloan Kettering Cancer Center, Lymphoma Division, New York, United States
Honglei Zhang
Andrew D. Zelenetz
11Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY