Asciminib monotherapy in patients with chronic-phase chronic myeloid leukemia with the T315I mutation after ≥1 prior tyrosine kinase inhibitor: 2-year follow-up results.

Autor: Cortes JE; Georgia Cancer Center at Augusta University, Augusta, GA, USA. Jorge.Cortes@Augusta.edu., Sasaki K; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Kim DW; Uijeongbu Eulji Medical Center, Geumo-dong, Uijeongbu-si, South Korea., Hughes TP; South Australian Health and Medical Research Institute and University of Adelaide, Adelaide, SA, Australia., Etienne G; Department of Hematology, Institut Bergonié, Bordeaux, France., Mauro MJ; Myeloproliferative Neoplasms Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Hochhaus A; Hematology/Oncology, Universitätsklinikum Jena, Jena, Germany., Lang F; Department of Medicine, Hematology and Oncology, Goethe University Hospital, Frankfurt, Germany., Heinrich MC; Portland VA Health Care System and OHSU Department of Medicine, Division of Hematology and Oncology, Knight Cancer Institute, Portland, OR, USA., Breccia M; Department of Translational and Precision Medicine-Az., Policlinico Umberto I-Sapienza University, Rome, Italy., Deininger M; Versiti Blood Research Institute, Milwaukee, WI, USA., Goh YT; Department of Haematology, Singapore General Hospital, Bukit Merah, Singapore., Janssen JJWM; Radboud University Medical Center, Nijmegen, The Netherlands., Talpaz M; Division of Hematology-Oncology, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA., de Soria VGG; Hospital Universitario La Princesa, Madrid, Spain., le Coutre P; Department of Oncology and Hematology, Charité - Universitätsmedizin Berlin, Berlin, Germany., DeAngelo DJ; Dana-Farber Cancer Institute, Boston, MA, USA., Damon A; Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA., Cacciatore S; Novartis Pharma AG, Basel, Switzerland., Polydoros F; Novartis Pharma AG, Basel, Switzerland., Agrawal N; Novartis Pharma AG, Basel, Switzerland., Rea D; Department of Hématologie, Hôpital Saint-Louis, Paris, France.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2024 Jul; Vol. 38 (7), pp. 1522-1533. Date of Electronic Publication: 2024 May 16.
DOI: 10.1038/s41375-024-02278-8
Abstrakt: Asciminib targets the BCR::ABL1 myristoyl pocket, maintaining activity against BCR::ABL1 T315I , which is resistant to most approved adenosine triphosphate-competitive tyrosine kinase inhibitors. We report updated phase I results (NCT02081378) assessing safety/tolerability and antileukemic activity of asciminib monotherapy 200 mg twice daily in 48 heavily pretreated patients with T315I-mutated chronic-phase chronic myeloid leukemia (CML-CP; data cutoff: January 6, 2021). With 2 years' median exposure, 56.3% of patients continued receiving asciminib. Overall, 62.2% of evaluable patients achieved BCR::ABL1 ≤1% on the International Scale (IS); 47.6% and 81.3% of ponatinib-pretreated and -naive patients, respectively, achieved BCR::ABL1 IS  ≤1%. Of 45 evaluable patients, 48.9% achieved a major molecular response (MMR, BCR::ABL1 IS  ≤0.1%), including 34.6% and 68.4% of ponatinib-pretreated and -naive patients, respectively. MMR was maintained until data cutoff in 19 of 22 patients who achieved it. The most common grade ≥3 adverse events (AEs) included increased lipase level (18.8%) and thrombocytopenia (14.6%). Five (10.4%) patients experienced AEs leading to discontinuation, including 2 who discontinued asciminib and died due to COVID-19; these were the only deaths reported. These results show asciminib's effectiveness, including in almost 50% of ponatinib pretreated patients, and confirm its risk-benefit profile, supporting its use as a treatment option for T315I-mutated CML-CP.
(© 2024. The Author(s).)
Databáze: MEDLINE
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