Ibrutinib Plus Venetoclax for First-Line Treatment of Chronic Lymphocytic Leukemia: Primary Analysis Results From the Minimal Residual Disease Cohort of the Randomized Phase II CAPTIVATE Study
| Autor: | Wierda, W. G., Allan, J. N., Siddiqi, T., Kipps, T. J., Opat, S., Tedeschi, Alessandra, Badoux, X. C., Kuss, B. J., Jackson, S., Moreno, Carol, Jacobs, R. M. D., Pagel, J. M., Flinn, I., Pak, Y., Zhou, Cathy, Szafer-Glusman, E., Ninomoto, J., Dean, James P, James, D. F., Ghia, Paolo, Tam, C. S., Universitat Autònoma de Barcelona |
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| Přispěvatelé: | Wierda, William G, Allan, John N, Siddiqi, Tanya, Kipps, Thomas J, Opat, Stephen, Tedeschi, Alessandra, Badoux, Xavier C, Kuss, Bryone J, Jackson, Sharon, Moreno, Carol, Jacobs, Ryan, Pagel, John M, Flinn, Ian, Pak, Yvonne, Zhou, Cathy, Szafer-Glusman, Edith, Ninomoto, Joi, Dean, James P, James, Danelle F, Ghia, Paolo, Tam, Constantine S |
| Rok vydání: | 2021 |
| Předmět: |
Male
Oncology Cancer Research Neoplasm Residual Lymphoma Chronic lymphocytic leukemia Phases of clinical research Cohort Studies chemistry.chemical_compound Piperidines Antineoplastic Combined Chemotherapy Protocols Medicine Chronic Cancer Sulfonamides Leukemia Heterocyclic Hematology Middle Aged Lymphocytic Residual 6.1 Pharmaceuticals Ibrutinib Cohort Female Adult medicine.medical_specialty Clinical Trials and Supportive Activities Clinical Sciences Oncology and Carcinogenesis Bridged Bicyclo Compounds Rare Diseases Clinical Research Internal medicine Humans Oncology & Carcinogenesis Aged business.industry Venetoclax Adenine B-Cell Evaluation of treatments and therapeutic interventions Bridged Bicyclo Compounds Heterocyclic medicine.disease Leukemia Lymphocytic Chronic B-Cell Survival Analysis Minimal residual disease Discontinuation First line treatment Orphan Drug chemistry Neoplasm business |
| Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol 39, iss 34 Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona JOURNAL OF CLINICAL ONCOLOGY r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.21.00807 |
| Popis: | PURPOSE CAPTIVATE ( NCT02910583 ), a randomized phase II study, evaluates minimal residual disease (MRD)-guided treatment discontinuation following completion of first-line ibrutinib plus venetoclax treatment in patients with chronic lymphocytic leukemia (CLL). METHODS Previously untreated CLL patients age < 70 years received three cycles of ibrutinib and then 12 cycles of combined ibrutinib plus venetoclax. Patients in the MRD cohort who met the stringent random assignment criteria for confirmed undetectable MRD (Confirmed uMRD) were randomly assigned 1:1 to double-blind placebo or ibrutinib; patients without Confirmed uMRD (uMRD Not Confirmed) were randomly assigned 1:1 to open-label ibrutinib or ibrutinib plus venetoclax. Primary end point was 1-year disease-free survival (DFS) rate with placebo versus ibrutinib in the Confirmed uMRD population. Secondary end points included response rates, uMRD, and safety. RESULTS One hundred sixty-four patients initiated three cycles of ibrutinib lead-in. After 12 cycles of ibrutinib plus venetoclax, best uMRD response rates were 75% (peripheral blood) and 68% (bone marrow). Patients with Confirmed uMRD were randomly assigned to receive placebo (n = 43) or ibrutinib (n = 43); patients with uMRD Not Confirmed were randomly assigned to ibrutinib (n = 31) or ibrutinib plus venetoclax (n = 32). Median follow-up was 31.3 months. One-year DFS rate was not significantly different between placebo (95%) and ibrutinib (100%; arm difference: 4.7% [95% CI, –1.6 to 10.9]; P = .15) in the Confirmed uMRD population. After ibrutinib lead-in tumor debulking, 36 of 40 patients (90%) with high tumor lysis syndrome risk at baseline shifted to medium or low tumor lysis syndrome risk categories. Adverse events were most frequent during the first 6 months of ibrutinib plus venetoclax and generally decreased over time. CONCLUSION The 1-year DFS rate of 95% in placebo-randomly assigned patients with Confirmed uMRD suggests the potential for fixed-duration treatment with this all-oral, once-daily, chemotherapy-free regimen in first-line CLL. |
| Databáze: | OpenAIRE |
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