All-Oral Treatment of Newly Diagnosed Acute Myeloid Leukemia
47% of the patients in this study had complete response (CR) on all oral regimen of decitabine–cedazuridine 5 days every 28 days plus venetoclax 400mg daily.
Asciminib demonstrates superior efficacy and safety in newly diagnosed chronic myeloid leukemia in the ASC4FIRST trial Open Access
Author(s): Cortes, Jorge E.1; Hughes, Timothy P.2; Wang, Jianxiang3; Kim, Dong-Wook4; Kim, Dennis Dong Hwan5; Mayer, Jiri6; Goh, Yeow-Tee7; le Coutre, Philipp8; Etienne, Gabriel9; Kim, Inho10; Andorsky, David J.11; Bombaci, Felice12; Issa, Ghayas C.13; Takahashi, Naoto14; Kapoor, Shruti15; Jinwal, Rajendra16; Malek, Kamel16; McCulloch, Tracey16; Yau, Lillian16; Larson, Richard A.17; Hochhaus, Andreas18;
Source: Blood (2026) 147 (13): 1433–1446
Dr. Anjan Patel's Thoughts
This is starting to look like a real frontline disruptor in chronic myeloid leukemia (CML), asciminib showing a pretty striking ~22% absolute improvement in MMR at 96 weeks vs investigator-selected TKIs (and nearly 30% over imatinib) with a cleaner tolerability profile makes a strong case for moving beyond ATP-competitive tyrosine kinase inhibitors (TKIs) upfront. The efficacy signal is consistent across depths of response and durability looks excellent, with fewer discontinuations, overall survival (OS) will take time, but this feels very competitive as a new standard option.
ABSTRACT
Many patients receiving frontline tyrosine kinase inhibitors (TKIs) for chronic-phase chronic myeloid leukemia (CML-CP) experience inadequate disease control and/or adverse events (AEs) that impair quality of life. Treatments offering optimal efficacy, safety, and tolerability will support long-term therapy. In the primary analysis from the ASC4FIRST trial, a phase 3 randomized trial comparing asciminib with investigator-selected TKIs (IS-TKIs) in newly diagnosed CML-CP, asciminib demonstrated superior efficacy vs all IS-TKIs and vs imatinib in the imatinib stratum, meeting both primary objectives. In the secondary analysis (2.2 years’ median follow-up), major molecular response (MMR) rate at week 96 was 74.1% with asciminib vs 52.0% with IS-TKIs (treatment difference, 22.4% [95% confidence interval (CI), 13.6-31.3]; 1-sided P< .001) and 76.2% with asciminib vs 47.1% with imatinib in the imatinib stratum (treatment difference, 29.7% [95% CI, 17.6-41.8]; 1-sided P< .001), meeting both key secondary objectives. MMR rate was 72.0% with asciminib vs 56.9% with second-generation (2G) TKIs (treatment difference, 15.1% [95% CI, 2.3-28.0]; 1-sided P< .05), suggesting possible clinical benefit, although the study was not designed to formally confirm statistical significance for this secondary end point. Safety/tolerability remained favorable with asciminib vs IS-TKIs. Dose reductions and interruptions, respectively, occurred with asciminib (18.5%; 46.5%), imatinib (23.2%; 47.5%), and 2G TKIs (54.9%; 63.7%). The hazard ratio for time to discontinuation of treatment due to AEs for asciminib vs 2G TKIs was 0.46 (95% CI, 0.215-0.997). With longer follow-up, asciminib continued to demonstrate a favorable benefit-risk profile over IS-TKIs and imatinib, supporting its potential as a treatment option for newly diagnosed CML-CP. This trial was registered at www.clinicaltrials.gov as NCT04971226.
Author Affiliations
1Department of Medicine, Georgia Cancer Center Augusta University, Augusta, GA; 2Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute and University of Adelaide, Adelaide, Australia; 3State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China; 4Department of Hematology, Uijeongbu Eulji Medical Center, Uijeongbu-si, Republic of Korea; 5Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada; 6Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Masaryk University Brno, Brno, Czech Republic; 7Department of Hematology, Singapore General Hospital, Singapore; 8Department of Oncology and Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany; 9Hematology Department, Institut Bergonié, Bordeaux, France; 10Department of Internal Medicine, Seoul National University Hospital, Biomedical Research Institute, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; 11Rocky Mountain Cancer Centers, Boulder, CO; 12CML Patients Group, CML Advocates Network, Turin, Italy; 13Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; 14Department of Hematology, Akita University, Akita City, Japan; 15Novartis Pharmaceuticals, East Hanover, NJ; 16Novartis Pharma AG, Basel, Switzerland; 17Department of Medicine, The University of Chicago, Chicago, IL; 18Department of Hematology/Oncology, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, GermanyRelated Articles
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