Talha Badar: CML review series
Talha Badar, Specialist in Hematology Oncology, shared a post on X:
“Continuing CML review series: CML and clonal hematopoiesis–
–Somatic variants and their impact on outcome.
– Does CML arises from antecedent CHIP?
– What are the somatic variants acquired on TKI therapy association with inferior outcome.
“Continuing CML review series from last weekend.
Will briefly discuss treatment free remission (TFR) in CML-CP.
Successful treatment of CML-CP has led to possibility of TFR. Deep Molecular remission (DMR; +2 years) achieve with TKIs resulted successful TFR in 40-50% of patients, success rate is higher if patient remained on TKI for longer with deeper molecular response.
Clinical trials:
Saussele et al. (EURO-SKI) Lancet Onc 2018, Ross et al (TWISTER) Blood 2013, Hochhaus et al (ENESTfreedom) Leukemia 2017, Atallah et al (LAST). JAMA Oncology.”
“Choice of frontline therapy for CML in chronic phase:
Long-term follow up data from pivotal trials.
•Aim of therapy:
-Survival
-Achievement of MMR with opportunities for TFR.
-Minimal or manageable toxicity.
•Practical consideration
-Cost of therapy
-Best suited therapy based on pt profile/co-morbidities.”
“Targeted deep sequencing was performed on 300 CML-CP samples from 100 pts, 37 patients carry somatic mutation. Mutation persistence after TKI does not correspond to Rx response (image below); 10% of pts had mutation persistence after response. Acquisition of new mutations example ASXL1 assoc. with inferior outcome.”
“Mutations associated with epigenetic regulation (TET2, ASXL1, DNMT3A) at diagnosis were associated with:
-Inferior CCyR at 12 months.
-Inferior MMR at 2 years. Inferior MR 4.5 at 3 years.”
“CML arising from antecedent CHIP Another study that revealed individual hematopoietic colonies at diagnosis were part of the Ph-positive clones. And response to TKI is irrespective of certain mutations present at diagnosis.”
“CML-CP and ASXL1 mutation
Study showing 53/222 (24%) patients harboring somatic variants, ASXL1 most common and associated with inferior molecular response.
“Summary: CML-CP and clonal hematopoiesis.
Dr. Talha Badar, MD, is a specialist in Hematology Oncology based in Mayo Clinic, Jacksonville, Florida. His primary areas of expertise include Leukemia, particularly Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Acute Lymphoblastic Leukemia (ALL), and Bone Marrow Transplantation. Over his career, he has actively contributed to clinical research and clinical trials.
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