BTK inhibitor therapy is effective in patients with CLL resistant to venetoclax.

Autor:	Lin VS; Department of Clinical Haematology, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia.; Blood Cells and Blood Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia., Lew TE; Department of Clinical Haematology, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.; Blood Cells and Blood Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia., Handunnetti SM; Department of Clinical Haematology, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia., Blombery P; Department of Clinical Haematology, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia.; Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia., Nguyen T; Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia., Westerman DA; Department of Clinical Haematology, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia.; Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia., Kuss BJ; Department of Haematology and Genetic Pathology, Flinders University, Adelaide, SA, Australia; and., Tam CS; Department of Clinical Haematology, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia.; Department of Haematology, St Vincent's Hospital Melbourne, Fitzroy, VIC, Australia., Roberts AW; Department of Clinical Haematology, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia.; Blood Cells and Blood Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia., Seymour JF; Department of Clinical Haematology, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia., Anderson MA; Department of Clinical Haematology, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.; Blood Cells and Blood Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2020 Jun 18; Vol. 135 (25), pp. 2266-2270.
DOI:	10.1182/blood.2020004782
Abstrakt:	Highly active BTK inhibitors (BTKis) and the BCL2 inhibitor venetoclax have transformed the therapeutic landscape for chronic lymphocytic leukemia (CLL). Results of prospective clinical trials demonstrate the efficacy of venetoclax to salvage patients with disease progression on BTKis, but data on BTKi therapy after disease progression on venetoclax are limited, especially regarding durability of benefit. We retrospectively evaluated the records of 23 consecutive patients with relapsed/refractory CLL who received a BTKi (ibrutinib, n = 21; zanubrutinib, n = 2) after stopping venetoclax because of progressive disease. Median progression-free survival (PFS) and median overall survival after BTKi initiation were 34 months (range, <1 to 49) and 42 months (range, 2-49), respectively. Prior remission duration ≥24 months and attainment of complete remission or undetectable measurable residual disease on venetoclax were associated with longer PFS after BTKi salvage (P = .044 and P = .029, respectively). BTKi therapy achieved durable benefit for patients with the BCL2 Gly101Val venetoclax resistance mutation (estimated 24-month PFS, 69%). At a median survivor follow-up of 33 months (range, 2-53), 11 patients remained on BTKi and 12 had stopped therapy because of disease progression (n = 8) or toxicity (n = 4). Our findings indicate that BTKi therapy can provide durable CLL control after disease progression on venetoclax. (© 2020 by The American Society of Hematology.)
Databáze:	MEDLINE
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