Selected chronic myeloid leukemia (CML) patients may discontinue their tyrosine kinase inihibitor (TKI) in an attempt to achieve sustained treatment-free remission (TFR), which mitigates therapy-related side effects and limits treatment costs. TFR has been extensively studied following the discontinuation of adenosine triphosphate (ATP) - competitive TKI. However, there is minimal data concerning TFR after the discontinuation of the novel TKI asciminib. Here, we present two CML patients intolerant to multiple ATP-competitive TKIs who achieved a deep molecular response (DMR) during asciminib treatment and sustained this remission after asciminib discontinuation. One of the cases developed transient myalgia and arthralgia after asciminib discontinuation consistent with a TKI withdrawal syndrome. Both patients have been free of molecular relapse for more than at least 8 months after TKI discontinuation without increase in molecular BCR::ABL1 signal. These two cases provide proof of principle that sustained TFR after discontinuing asciminib in CML patients is feasible.
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http://dx.doi.org/10.1007/s00277-024-06170-4 | DOI Listing |
Ann Hematol
January 2025
Department of internal medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands.
Selected chronic myeloid leukemia (CML) patients may discontinue their tyrosine kinase inihibitor (TKI) in an attempt to achieve sustained treatment-free remission (TFR), which mitigates therapy-related side effects and limits treatment costs. TFR has been extensively studied following the discontinuation of adenosine triphosphate (ATP) - competitive TKI. However, there is minimal data concerning TFR after the discontinuation of the novel TKI asciminib.
View Article and Find Full Text PDFJ Hematol Oncol
December 2024
Georgia Cancer Center, Augusta, GA, USA.
Background: Up to 65% of patients with chronic myeloid leukemia (CML) who are treated with imatinib do not achieve sustained deep molecular response, which is required to attempt treatment-free remission. Asciminib is the only approved BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket. This unique mechanism of action allows asciminib to be combined with adenosine triphosphate-competitive tyrosine kinase inhibitors to prevent resistance and enhance efficacy.
View Article and Find Full Text PDFInt J Hematol
November 2024
Department of Hematology and Clinical Immunology, Yokohama City University School of Medicine, Yokohama, Japan.
Although tyrosine kinase inhibitors (TKIs) have improved the prognosis of chronic myeloid leukemia (CML), some patients do not respond to TKIs. We evaluated 21 patients with CML treated with asciminib, which is effective in heavily pretreated patients. The median age was 63 years (range 25-82).
View Article and Find Full Text PDFClin Lymphoma Myeloma Leuk
January 2025
Department of Drug Discovery and Biomedical Sciences, Faculty of Medicine, Saga University, Saga, Japan; Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
The survival outcomes of patients with chronic myeloid leukemia (CML) have significantly improved due to the introduction of adenosine triphosphate (ATP) -competitive ABL1 tyrosine kinase inhibitors (TKIs). However, several patients with CML eventually develop treatment resistance or intolerance during the course of ATP-competitive ABL1 TKI treatment. ABL1 TKIs inhibit other tyrosine kinases via their off-target effects.
View Article and Find Full Text PDFClin Lymphoma Myeloma Leuk
September 2024
Novartis Pharmaceuticals Corporation, East Hanover, NJ.
Background: Tyrosine kinase inhibitors (TKIs) are the mainstay treatment for chronic myeloid leukemia in chronic phase (CML-CP). Asciminib, an ABL/BCR::ABL1 inhibitor which binds to the myristoyl pocket, was recently approved in the US for patients with CML-CP previously treated with ≥2 TKIs or with the T315I mutation. This study described treatment patterns and real-world clinical outcomes among patients with CML-CP treated with asciminib in US clinical practice.
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