CML-466 Asciminib Provides Durable Molecular Responses in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With the T315I Mutation: Updated Efficacy and Safety Data From a Phase I Trial
Clinical lymphoma, myeloma & leukemia
; 22 Suppl 2:S300, 2022.
Article
in English
| MEDLINE | ID: covidwho-2050120
ABSTRACT
CONTEXT In CML-CP, the BCRABL1 T315I mutation confers resistance to previously approved ATP-competitive tyrosine kinase inhibitors (TKIs), except ponatinib and olverembatinib. In a previous analysis of the phase I, dose-escalation trial X2101, asciminib-a BCRABL1 inhibitor that binds to the ABL myristoyl pocket-demonstrated efficacy and a favorable safety profile in heavily pretreated patients with T315I-mutated CML. We report updated efficacy and safety data in patients with CML-CP with the T315I mutation (data cutoff January 6, 2021). OBJECTIVE:
Provide updated safety and efficacy data for patients with T315I-mutated CML-CP after added exposure.DESIGN:
Patients with T315I-mutated CML-CP and treated with >=1 prior TKI were enrolled and received asciminib 200mg twice daily (BID).RESULTS:
48 patients were included;25 patients (52.1%) received >=3 prior TKIs. At data cutoff, treatment was ongoing in 27 patients (56.3%). 45 of 48 patients were evaluable (BCRABL1IS >0.1% at baseline) for major molecular response (MMR);3 were excluded for BCRABL1 atypical transcripts. Among evaluable patients, 19 (42.2%) achieved MMR by week 24 and 22 (48.9%) by week 96. Evaluable patients included 26 ponatinib-pretreated and 19 ponatinib-naive patients;34.6% and 68.4%, respectively, achieved MMR by week 96. The probability of maintaining MMR for >=96 weeks was 84% (95% CI, 68.1%-100.0%). 23 of 37 patients (62.2%) with BCRABL1IS >1% at baseline achieved BCRABL1IS <=1% by week 96. The safety/tolerability profile of asciminib remained favorable after =9 months of added exposure (median duration of exposure, 2.08 years;range, 0.04-4.13 years). The most common (>=10%) grade >=3 adverse events (AEs) were lipase increase (18.8%, all asymptomatic elevations) and thrombocytopenia (14.6%). Arterial occlusive events occurred in 4 patients (8.3%);none led to dose adjustment/interruption/discontinuation. AEs leading to discontinuation occurred in 5 patients (10.4%). Only 2 study deaths, both due to COVID-19, occurred in this patient population.CONCLUSIONS:
After a median exposure of >2 years, asciminib monotherapy 200mg BID exhibited a sustained, favorable safety profile and clinical efficacy in patients with T315I-mutated CML-CP-a population with high unmet medical need. This updated analysis confirms asciminib as a treatment option for patients with T315I-mutated CML-CP, including those previously treated with ponatinib.
Adenosine Triphosphate/pd [Pharmacology]; Adenosine Triphosphate/tu [Therapeutic Use]; Antineoplastic Agents/tu [Therapeutic Use]; *Antineoplastic Agents; *covid-19; Drug Resistance, Neoplasm; Fusion Proteins, bcr-abl; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/dt [Drug Therapy]; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/ge [Genetics]; *Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lipase/ge [Genetics]; Lipase/pd [Pharmacology]; Lipase/tu [Therapeutic Use]; Mutation; Niacinamide/aa [Analogs & Derivatives]; Protein Kinase Inhibitors/ae [Adverse Effects]; Pyrazoles; 0 (Antineoplastic Agents); 0 (Protein Kinase Inhibitors); 0 (Pyrazoles); 0 (asciminib); 25X51I8RD4 (Niacinamide); 8L70Q75FXE (Adenosine Triphosphate); EC 2-7-10-2 (Fusion Proteins, bcr-abl); EC 3-1-1-3 (Lipase)
Full text:
Available
Collection:
Databases of international organizations
Database:
MEDLINE
Type of study:
Randomized controlled trials
Language:
English
Journal:
Clinical lymphoma, myeloma & leukemia
Year:
2022
Document Type:
Article
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