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
Wierda, W. G. (University of Texas.)
Allan, J. N. (Weill Cornell Medicine)
Siddiqi, Tanya (City of Hope National Medical Center)
Kipps, Thomas J (University of California San Diego. Moores Cancer Center)
Opat, S. (Monash University)
Tedeschi, Alessandra (ASST Grande Ospedale Metropolitano Niguarda)
Badoux, X. C. (Ministry of Health)
Kuss, B. J. (Flinders University. Medical Centre)
Jackson, Sharon (Middlemore Hospital)
Moreno, Carol (Institut d'Investigació Biomèdica Sant Pau)
Jacobs, R. M. D. (Levine Cancer Institute)
Pagel, J. M. (Swedish Cancer Institute. Center for Blood Disorders and Stem Cell Transplantation)
Flinn, I. (Sarah Cannon Research Institute. Tennessee Oncology)
Pak, Y. (Pharmacyclics LLC. AbbVie Company)
Zhou, Cathy (Pharmacyclics LLC. AbbVie Company)
Szafer-Glusman, E. (Pharmacyclics LLC. AbbVie Company)
Ninomoto, J. (Pharmacyclics LLC. AbbVie Company)
Dean, James P (Pharmacyclics LLC. AbbVie Company)
James, D. F. (Pharmacyclics LLC. AbbVie Company)
Ghia, Paolo (Università Vita-Salute San Raffaele. IRCCS Ospedale San Raffaele)
Tam, C. S. (Peter MacCallum Cancer Center. St Vincent's Hospital. University of Melbourne)
Universitat Autònoma de Barcelona

Fecha:	2021
Resumen:	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 5 43) or ibrutinib (n 5 43); patients with uMRD Not Confirmed were randomly assigned to ibrutinib (n 5 31) or ibrutinib plus venetoclax (n 5 32). Median followup 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 5. 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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Adenine ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; Bridged Bicyclo Compounds, Heterocyclic ; Cohort Studies ; Female ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; Male ; Middle Aged ; Neoplasm, Residual ; Piperidines ; Sulfonamides ; Survival Analysis
Publicado en:	Journal of Clinical Oncology, Vol. 39 Núm. 34 (january 2021) , p. 3853-3865, ISSN 1527-7755

DOI: 10.1200/JCO.21.00807
PMID: 34618601

15 p, 664.9 KB

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