Asciminib monotherapy in patients with CML-CP without BCR::ABL1 T315I mutations treated with at least two prior TKIs: 4-year phase 1 safety and efficacy results.
Michael J MauroTimothy P HughesDong-Wook KimDelphine ReaJorge E CortesAndreas HochhausKoiji SasakiMassimo BrecciaMoshe TalpazOliver OttmannHironobu MinamiYeow Tee GohDaniel J DeAngeloMichael C HeinrichValle Gómez-García de SoriaPhilipp le CoutreFrancois-Xavier MahonJeroen J W M JanssenMichael DeiningerNaranie ShanmuganathanMark Blaine GeyerSilvia CacciatoreFotis PolydorosNithya AgrawalMatthias HochFabian LangPublished in: Leukemia (2023)
Asciminib is approved for patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia (CML-CP) who received ≥2 prior tyrosine kinase inhibitors or have the T315I mutation. We report updated results of a phase 1, open-label, nonrandomized trial (NCT02081378) assessing the safety, tolerability, and antileukemic activity of asciminib monotherapy 10-200 mg once or twice daily in 115 patients with CML-CP without T315I (data cutoff: January 6, 2021). After ≈4-year median exposure, 69.6% of patients remained on asciminib. The most common grade ≥3 adverse events (AEs) included increased pancreatic enzymes (22.6%), thrombocytopenia (13.9%), hypertension (13.0%), and neutropenia (12.2%); all-grade AEs (mostly grade 1/2) included musculoskeletal pain (59.1%), upper respiratory tract infection (41.7%), and fatigue (40.9%). Clinical pancreatitis and arterial occlusive events (AOEs) occurred in 7.0% and 8.7%, respectively. Most AEs occurred during year 1; the subsequent likelihood of new events, including AOEs, was low. By data cutoff, among patients without the indicated response at baseline, 61.3% achieved BCR::ABL1 ≤ 1%, 61.6% achieved ≤0.1% (major molecular response [MMR]), and 33.7% achieved ≤0.01% on the International Scale. MMR was maintained in 48/53 patients who achieved it and 19/20 who were in MMR at screening, supporting the long-term safety and efficacy of asciminib in this population.
Keyphrases
- chronic myeloid leukemia
- open label
- phase iii
- respiratory tract
- phase ii
- clinical trial
- end stage renal disease
- study protocol
- newly diagnosed
- electronic health record
- phase ii study
- blood pressure
- ejection fraction
- combination therapy
- chronic kidney disease
- big data
- peritoneal dialysis
- machine learning
- neuropathic pain
- pain management
- prognostic factors
- acute lymphoblastic leukemia
- single molecule
- squamous cell carcinoma
- patient reported outcomes
- artificial intelligence
- spinal cord injury
- double blind
- genome wide
- sleep quality
- deep learning
- spinal cord
- locally advanced