Immune restoration with ibrutinib plus venetoclax in first-line chronic lymphocytic leukemia : the phase 2 CAPTIVATE study
Moreno, Carol (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Solman, Isabelle G. (Pharmacyclics LLC. an AbbVie Company)
Tam, Constantine S. (Monash University)
Grigg, Andrew (Austin Hospital)
Scarfò, Lydia (Università Vita Salute San Raffaele)
Kipps, Thomas J. (University of California. Moores Cancer Center)
Srinivasan, Srimathi (Janssen Research & Development)
Mali, Raghuveer Singh (Pharmacyclics LLC. an AbbVie Company)
Zhou, Cathy (Pharmacyclics LLC. an AbbVie Company)
Dean, James P. (Pharmacyclics LLC. an AbbVie Company)
Szafer Glusman, Edith (Pharmacyclics LLC. an AbbVie Company)
Choi, Michael (University of California)
Data: |
2023 |
Resum: |
We evaluated immune cell subsets in patients with chronic lymphocytic leukemia (CLL) who received first-line therapy with 3 cycles of ibrutinib then 13 cycles of ibrutinib plus venetoclax in the minimal residual disease (MRD) cohort of the CAPTIVATE study (NCT02910583). Patients with Confirmed undetectable MRD (uMRD) were randomly assigned to placebo or ibrutinib groups; patients without Confirmed uMRD were randomly assigned to ibrutinib or ibrutinib plus venetoclax groups. We compared immune cell subsets in samples collected at 7 time points with age-matched healthy donors. CLL cells decreased within 3 cycles after venetoclax initiation; from cycle 16 onward, levels were similar to healthy donor levels (HDL; ≤0. 8 cells per μL) in patients with Confirmed uMRD and slightly above HDL in patients without Confirmed uMRD. By 4 months after cycle 16, normal B cells had recovered to HDL in patients randomly assigned to placebo. Regardless of randomized treatment, abnormal counts of T cells, classical monocytes, and conventional dendritic cells recovered to HDL within 6 months (median change from baseline −49%, +101%, and +91%, respectively); plasmacytoid dendritic cells recovered by cycle 20 (+598%). Infections generally decreased over time regardless of randomized treatment and were numerically lowest in patients randomly assigned to placebo within 12 months after cycle 16. Sustained elimination of CLL cells and recovery of normal B cells were confirmed in samples from patients treated with fixed-duration ibrutinib plus venetoclax in the GLOW study (NCT03462719). These results demonstrate promising evidence of restoration of normal blood immune composition with ibrutinib plus venetoclax. |
Nota: |
Fundació Carreras |
Nota: |
This study was supported by Pharmacyclics LLC, an AbbVie Company. |
Drets: |
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. |
Llengua: |
Anglès |
Document: |
Article ; recerca ; Versió publicada |
Matèria: |
Lymphoid neoplasia |
Publicat a: |
Blood advances, Vol. 7 Núm. 18 (26 2023) , p. 5294-5309, ISSN 2473-9537 |
DOI: 10.1182/bloodadvances.2023010236
PMID: 37315225
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Registre creat el 2024-02-19, darrera modificació el 2024-05-04