Chronic Myeloid Leukemia (CML) is initiated by the BCR::ABL1 gene fusion. While this genetic mutation is the primary driver of the disease, recent research indicates that additional genetic abnormalities (AGA) can significantly impact treatment success. Understanding the prevalence and effect of these AGAs at the time of diagnosis is vital for effective patient management. A recent study investigated the role of these additional genetic factors in patients with chronic phase CML undergoing treatment with imatinib, a common first-line therapy.
This research, involving 210 patients in the TIDEL-II trial, aimed to determine if AGAs present at initial diagnosis influenced patient outcomes, even with a proactive treatment approach. The study meticulously analyzed survival rates, including overall survival, progression-free survival, and failure-free survival. They also monitored for the development of BCR::ABL1 kinase domain mutations, which can lead to treatment resistance. Molecular responses, key indicators of treatment effectiveness, were assessed by measuring BCR::ABL1 levels, specifically looking at major molecular response (MMR), MR4, and MR4.5. The presence of AGA, encompassing variants in known cancer-related genes and unique rearrangements associated with the Philadelphia chromosome, was thoroughly evaluated.
The study revealed that a significant proportion of patients, 31%, presented with AGA at diagnosis. Specifically, potentially harmful variants in cancer-related genes were found in 16% of patients, and structural rearrangements linked to the Philadelphia chromosome were observed in 18%. Multivariable analysis highlighted that the combination of these genetic abnormalities along with the EUTOS long-term survival clinical risk score were strong indicators of poorer molecular response and increased treatment failure. Importantly, even with a proactive treatment strategy using first-line imatinib, patients with AGA experienced less favorable response rates.
These findings underscore the critical importance of early diagnosis and proactive care in CML. Identifying AGAs at diagnosis allows for a more informed risk assessment and the potential for tailored treatment strategies beyond standard approaches. This study provides compelling evidence for incorporating comprehensive genomic assessment into the routine management of CML, emphasizing that Early Diagnosis And Proactive Care Are not just about starting treatment quickly, but also about understanding the individual genetic landscape of the disease to optimize outcomes. Genomically-based risk assessment should be considered to enhance treatment strategies and improve outcomes for patients with CML.
