Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research
Patients and Methods
We applied our in-house CML-specific smMIP panel with a limit of detection up to 0.2%. The panel encompasses 37 genes with 332 amplicon probes: epigenetic modifiers (n=7), activation signaling (n=12), myeloid transcription factor (TF; n=5), spliceosome (n=3), tumor suppressor (n=3), cohesion (n=4) and miscellaneous (n=3). Our cohort included 135 patients who attempted TKI DISC for TFR from 4 countries: Argentina (n=28, 20.7%), Brazil (n=30, 22.2%), Czechia (n=3, 2.2%), Canada (n=34, 54.8%). Disease characteristics and outcomes were evaluated and compared according to the mutation profiles prior to TKI DISC. Molecular relapse-free survival (RFS) was calculated from the date of TKI DISC to the date of confirmed loss of molecular response. An episode of major molecular response (MMR) loss or two consecutive episodes of molecular response loss of 4 logs or deeper response (MR4) constituted molecular relapse. Kaplan-Meier survival estimate was used to evaluate RFS and Cox’s proportional hazard regression model was applied.
Results
Median age was 55.5 years (25-72), 55% males, and Sokal Score risks rates were as follows: Low 51.8%, intermediate 26.8%, High 8.33%. All patients were in chronic phase at diagnosis. A total of 102 pts (78%) stopped Imatinib, while 24 pts (22%) stopped 2GTKI: Dasatinib (n=17) and Nilotinib (n=7). There was no difference in RFS between IM DISC vs. 2GTKI DISC: the patients who stopped IM showed RFS rate of 64.3% (40.9-80.4%) vs those who stopped 2GTKI showed 58% (48.5-67.7%; p=0.634). A total of 59 mutations were detected in 43 (31.9%) patients. TET2 was the most commonly mutated gene (n=15, 11.1%) followed by ASXL1 (n=10, 7.4%) and, DNMT3A (n=9, 6.7%). According to its biologic pathways of the mutation, mutations were detected in the Epigenetic modifiers (n=33, 56%) most frequently, followed by Cohesin (n=16, 27%), activated signaling (n=7, 12%), tumor suppressor (n=3, 5%) and splicing (n=1, 2%). According to the mutational profile before TKI DISC for the TFR attempt, no difference in RFS was observed according to the biological pathways of mutations or according to the presence of mutation (fig 1). Overall RFS at 1 year was 56% (95% CI [45.1-66.1%]) in patients without any mutations comparing to 67.5% (50.7-79.7%) in patients with mutation(s) (p=0.49; fig 2). The RFS rate at 1 year was 58.9% (48.3-68%) in patients with epigenetic mutations compared to 63.3% (43.6.-78.7%) in those without it (p=0.73). Even after adjustment for MR4 duration, we could not identify any predictive profile of RFS.
Conclusion
Somatic mutations were not infrequently detected in the patients qualified for TFR attempt using a technique detecting up to 0.2% VAF. Mutations in epigenetic genes were most frequently detected. However, it does not seem to have any predictive power for TFR success. Its biological relevance remains to be further investigated in future research.
Disclosures: Perusini: Pfizer: Consultancy. Pagnano: Wieth/Pfizer: Consultancy, Honoraria; GSK: Consultancy; Novartis: Consultancy, Honoraria; Astellas: Consultancy, Honoraria. Pavlovsky: Novartis, Pfizer, BMS, Pint Pharma: Speakers Bureau; Novartis, Pfizer: Membership on an entity's Board of Directors or advisory committees. Moiraghi: Takeda: Speakers Bureau; Pfizer: Speakers Bureau; Novartis: Speakers Bureau. Žácková: Angelini Pharma: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Kim: Novartis: Consultancy, Honoraria, Research Funding; BMS: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Paladin: Consultancy, Research Funding; Merck: Consultancy; Sanofi: Consultancy, Honoraria.
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