Zanubrutinib, obinutuzumab, and venetoclax for first-line treatment of mantle cell lymphoma with a TP53 mutation Journal Article
| Authors: | Kumar, A.; Soumerai, J.; Abramson, J. S.; Barnes, J. A.; Caron, P.; Chhabra, S.; Chabowska, M.; Dogan, A.; Falchi, L.; Grieve, C.; Haydu, J. E.; Johnson, P. C.; Joseph, A.; Kelly, H. E.; Labarre, A.; Lue, J. K.; Martignetti, R.; Mi, J.; Moskowitz, A.; Owens, C.; Plummer, S.; Puccio, M.; Salles, G.; Seshan, V.; Simkins, E.; Slupe, N.; Zhang, H.; Zelenetz, A. D. |
| Article Title: | Zanubrutinib, obinutuzumab, and venetoclax for first-line treatment of mantle cell lymphoma with a TP53 mutation |
| 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. © 2025 American Society of Hematology |
| Keywords: | adult; clinical article; treatment response; aged; gene mutation; overall survival; prednisone; constipation; drug tolerability; fatigue; neutropenia; cancer combination chemotherapy; diarrhea; drug efficacy; drug safety; drug withdrawal; hypertension; side effect; follow up; progression free survival; mantle cell lymphoma; multiple cycle treatment; phase 2 clinical trial; anemia; nausea; thrombocytopenia; myalgia; protein p53; abdominal pain; alanine aminotransferase blood level; arthralgia; aspartate aminotransferase blood level; dyspnea; fever; pneumonia; rash; alanine aminotransferase; aspartate aminotransferase; maculopapular rash; cancer regression; minimal residual disease; pneumothorax; multicenter study; urinary tract infection; retina detachment; headache; gastroesophageal reflux; lung infection; flatulence; growth factor; epistaxis; atrial fibrillation; disease specific survival; upper respiratory tract infection; appendicitis; multiple organ failure; platelet count; overall response rate; contusion; first-line treatment; faintness; infusion related reaction; human; male; female; article; nocardiosis; obinutuzumab; venetoclax; zanubrutinib; coronavirus disease 2019 |
| Journal Title: | Blood |
| Volume: | 145 |
| Issue: | 5 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2025-01-30 |
| Start Page: | 497 |
| End Page: | 507 |
| Language: | English |
| DOI: | 10.1182/blood.2024025563 |
| PUBMED: | 39437708 |
| PROVIDER: | scopus |
| PMCID: | PMC11826521 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
