Immune restoration with ibrutinib plus venetoclax in first-line chronic lymphocytic leukemia: the phase 2 CAPTIVATE study

被引:11
作者
Moreno, Carol [1 ,11 ]
Solman, Isabelle G. [2 ]
Tam, Constantine S. [3 ,4 ]
Grigg, Andrew [5 ]
Scarfo, Lydia [6 ,7 ]
Kipps, Thomas J. [8 ]
Srinivasan, Srimathi [9 ]
Mali, Raghuveer Singh [2 ]
Zhou, Cathy [2 ]
Dean, James P. [2 ]
Szafer-Glusman, Edith [2 ]
Choi, Michael [10 ]
机构
[1] Autonomous Univ Barcelona, Hosp Santa Creu & St Pau, Josep Carreras Leukaemia Res Inst, Barcelona, Spain
[2] Pharmacyclics LLC, AbbVie Co, South San Francisco, CA USA
[3] Alfred Hosp, Dept Hematol, Melbourne, Vic, Australia
[4] Monash Univ, Melbourne, Vic, Australia
[5] Austin Hosp, Heidelberg, Vic, Australia
[6] Univ Vita Salute San Raffaele, Div Expt Oncol, Milan, Italy
[7] Osped San Raffaele, Ist Ricovero Cura Carattere Sci, Milan, Italy
[8] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA USA
[9] Janssen Res & Dev, Lower Gwynedd Township, PA USA
[10] Univ Calif San Diego, La Jolla, CA USA
[11] Autonomous Univ Barcelona, Hosp Santa Creu & St Pau, Carrer St Quinti 89, Barcelona 08041, Spain
关键词
T-CELLS; THERAPY;
D O I
10.1182/bloodadvances.2023010236
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 mu L) 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.
引用
收藏
页码:5294 / 5303
页数:10
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