Session: 632. Chronic Myeloid Leukemia: Therapy: Poster II
Hematology Disease Topics & Pathways:
Biological, Adult, Diseases, CML, Therapies, Biological Processes, Technology and Procedures, Study Population, Myeloid Malignancies, Clinically relevant, TKI, molecular testing
Methods: we analyzed the BCR-ABL1 RNA expression at therapy discontinuation (baseline), monthly during the first 6 months, bi-monthly between 6 and 12 months and three-monthly thereafter in 166 CML patients stopping imatinib (n=110) or 2nd generation TKI (n=56). Patients were divided among those who maintained MMR (group 1, n=120) and those who were deemed necessary to restart therapy for MMR loss (group 2, n=46). Molecular response was classified according to the standardized International Scale, DMR was defined as MR4 or deeper.
Results: median time from TKI stop and restart in group 2 was 5 months (range: 3-12). Mean BCR-ABL1 RNA expression at drug discontinuation for groups 1 and 2 was 0.0010±0.0020 and 0.0018±0.0029, respectively (p=0.052); difference in molecular response at stop did not reach statistical significance neither in the imatinib cohort (group 1: 0.0007±0.0019, group 2: 0.0016±0.0026; p=0.08) nor in the 2G-TKI one (group 1: 0.0015±0.0023, group 2: 0.0022±0.0032; p=0.64).
Mean BCR-ABL1 RNA levels one month after discontinuation were significantly higher in group 2 (0.0060±0.0107) than in group 1 (0.0010±0.0026; p=0.0005); this difference was confirmed and more evident two months after TKI stop as mean BCR-ABL1 value was 0.1354±0.4259 in group 2 compared to 0.0020±0.0076 in group 1 (p<0.0001) (Figure 1). The same trend was found in the imatinib group at month 1 (group 1: 0.0010±0.0028, group 2: 0.0059±0.0106; p=0.003) and at month 2 (group 1: 0.0021±0.0088, group 2: 0.0489±0.0913; p<0.0001) and in the 2G-TKI group at month 1 (group 1: 0.0009±0.0020, group 2: 0.0020±0.0037; p=0.014) and at month 2 (group 1: 0.0061±0.0113, group 2: 0.2707±0.6621; p=0.0001).
Moreover, even the slopes obtained with the values at baseline, one and two months (0.0006±0.0043 in group 1 vs 0.0237±0.0450 in group 2; p<0.0001) highlight the difference between patients with or without sustained MMR. These data were confirmed both for imatinib (-0.0043±0.0370 in group 1 vs 0.0237±0.0450 in group 2; p<0.0001) and for 2G-TKI (0.0002±0.0018 in group 1 vs 0.1132±0.3057 in group 2; p=0.0007).
For the determination of a threshold value of BCR-ABL1 RNA at one month after discontinuation, the ROC analysis was performed, defining an AUC=0.6430 (IC 95%: 0.5361-0.7498 p=0.0066): the cut-off value for BCR-ABL1 was defined as 0.0051%. The chosen range has 92.2% specificity, 31.7% sensitivity and a likelihood ratio of 4.087.
Conclusions: our data suggest that the chance of a successful TFR could be foreseen already at one month after TKI discontinuation, both for patients stopping imatinib or 2G-TKI. The 0.0051% BCR-ABL1 cut-off value identify patients who will maintain MMR; this could allow for a lengthening of molecular monitoring.
Disclosures: Krampera: Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Semenzato: Roche: Honoraria; Abbvie: Honoraria; Takeda: Honoraria.
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