Asciminib as Initial Therapy for Patients With Chronic Myeloid Leukemia in Chronic Phase

Inclusion Criteria: 1. Age ≥18 years old 2. Willing and able to give informed consent 3. Newly diagnosed with CML in chronic phase within 6 months from confirmed diagnosis via bone marrow biopsy/aspirate and have either the b3a2 (e14a2) or b2a2 (e13a2) variants that give rise to the p210 BCR::ABL1 protein. Subtype classification whether b3a2 (e14a2) or b2a2 (e13a2) is not required for study eligibility. 4. Minimal prior CML therapy with a TKI for less than or equal to 30 days. Treatment with hydroxyurea, busulfan, anagrelide or other non-specific chemotherapy agents is allowed with no time restrictions within the eligible time from diagnosis. 5. ECOG performance status 0-2 (appendix 1) 6. Adequate organ function: * AST and ALT \< 3 times the institutional upper limit of normal (ULN) * eGFR ≥ 30 mL/min as calculated using the 2021 chronic kidney disease epidemiology (CKD-EPI) creatinine equation (https://www.kidney.org/professionals/kdoqi/gfr\_calculator) * Total bilirubin \< 1.5 times the institutional ULN or \< 3.0 x the institutional ULN with Gilbert Syndrome (unless direct bilirubin is within normal limits) 7. Adequately controlled blood pressure, defined as systolic blood pressure of \<140 mmHq and diastolic of \<90 mmHg, at the time of enrollment. 8. Lipase ≤ 1.5 x ULN. For lipase \> ULN - ≤ 1.5 x ULN, value should be considered not clinically significant and not associated with risk factors for acute pancreatitis. 9. Creatine phosphokinase \< 2.5 x ULN 10. Female patients must meet one of the following: 1. Postmenopausal for at least one year before the screening visit, 2. Surgically sterile 3. If they are of childbearing potential, agree to practice two effective methods of contraception from the time of signing of the informed consent form through 90 days after the last dose of study drug, 4. Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable 5. Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable contraception methods.) 11. Male patients, even if surgically sterilized (i.e., status post vasectomy), must agree to one of the following: 1. Practice effective barrier contraception during the entire study treatment period and through 90 days after the last study drug dose 2. Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable 3. Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable methods of contraception.) Exclusion Criteria: 1. Patients with accelerated or blast phase CML (refer to appendix 4) 2. Active second malignancy requiring active treatment 3. History of recent (within 12 months) acute pancreatitis or chronic pancreatitis 4. Subjects who have previously received treatment with asciminib. 5. Subjects with PLT count \< 50,000 mm3 or ANC of \< 500 mm3 or Hemoglobin \< 8 g/dL 6. Cardiac or cardiac repolarization abnormality, including any of the following: 1. History within 6 months prior to starting study treatment of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG) 2. Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block) 3. QTcF at screening greater than or equal to 450 msec (male patients), greater than or equal to 460 msec (female patients) unless patient has a pacemaker 4. Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: i. Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia ii. Concomitant medication(s) with a "Known risk of Torsades de Pointes" per wwwcrediblemeds.org/ that cannot be discontinued or replace 7 days prior to starting study drug by safe alternative medication. iii. Inability to determine the QTcF interval 7. Pregnant or lactating 8. Taking a strong inhibitors or inducers of CYP3A4 or CYP3A4 substrates with narrow therapeutic index (refer to appendix 6) at time of enrollment 9. Unable to comply with lab appointment schedule and PRO assessments 10. Another investigational drug within 4 weeks of enrollment 11. Any serious medical or psychiatric illness that could, in the investigator's opinion, interfere with the completion of treatment according to this protocol 12. Patient has undergone a prior allogeneic stem cell transplant 13. Known clinical history of active HBV infection