Contributions
Abstract: PB1914
Type: Publication Only
Background
In BCR-ABL1 tyrosine kinase inhibitor (TKI) treated chronic phase chronic myeloid leukemia (CP-CML), early molecular response (EMR) at 3 months is currently identified as being one of the most important prognostic factors. Sokal risk score and dose intensity during first 3 months were strongly associated with achievement of EMR. As dasatinib is a novel, oral tyrosine kinase inhibitor with improved potency, identification of very early molecular response (VEMR) would be beneficial.
Aims
We evaluated the possibility of the VEMR at 1 month predicting long-term outcomes in newly diagnosed CP-CML patients treated with dasatinib.
Methods
In this multi-center, observational, open-label study, 102 patients with CP-CML were enrolled to receive dasatinib at a dose of 100 mg once daily. The primary end point was complete molecular response (CMR) by 18 months. Secondary end points including molecular response (MR) by 1, 3, 6, 12, 18, 24, 36 months, time to and duration of MMR and CMR, and safety were tested. A receiver operating characteristic (ROC) curve from BCR-ABL1 transcript level on Day+28 was calculated to predict EMR and MMR at specific timepoints.
Results
Median age was 49 years (19-81 years) and 61 patients were male. With median follow-up duration of 33.6 months (0.9-38.6 months), 71 (69.6%) out of 102 patients were still on dasatinib treatment and 31 patients discontinued due to disease progression (n=2) or treatment failure (n=3) or adverse events (n=18) or other reasons (n=8). The BCR-ABL1 mutations, assessed in 10 patients after dasatinib discontinuation, were detected in 3 patients which were all T315I mutation. The cumulative CMR by 18 months and MMR by 36 months were 20.5% and 84.8% respectively. In safety analyses, grade 3/4 thrombocytopenia (30.3%) was most common. Pleural effusion occurred in sixteen (15.6%) patients which were mostly grade 1/2. The cut-off value of BCR-ABL1 transcript on Day+28 was 40% by ROC curve analysis. Among 95 patients who had available molecular data of both D+28 and 12 months, fifty nine (62.1%) patients had less than 40% of BCR-ABL1 transcript (VEMR) on Day+28. Among them, 49 (83.1%) patients achieved MMR at 12 months. However, only 27.8% (10 out of 36 patients) of patients without VEMR achieved MMR (p<0.0001). Among 72 patients who had available molecular data of both D+28 and 36 months, forty-six (63.9%) patients achieved VEMR. In 46 VEMR patients, 43 (93.5%) patients achieved MMR at 36 months. However, 80.8% (21 out of 26 patients) of patients without VEMR achieved MMR (p=0.10). Three-year overall survival (OS) & progression-free survival (PFS) rates were 98.0% and 95.1%, respectively. Three-year PFS rates for VEMR and no VEMR group were 98.4% vs. 88.8% respectively (p=0.04).
Conclusion
Our study shows that VEMR at 1 month can be a strong predictor for further molecular responses as well as long-term outcome. Therefore, it would be helpful to monitor BCR-ABL1 transcript level at 1 month in patients who treated with more potent TKIs.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, Molecular response, prognosis, Tyrosine kinase inhibitor
Abstract: PB1914
Type: Publication Only
Background
In BCR-ABL1 tyrosine kinase inhibitor (TKI) treated chronic phase chronic myeloid leukemia (CP-CML), early molecular response (EMR) at 3 months is currently identified as being one of the most important prognostic factors. Sokal risk score and dose intensity during first 3 months were strongly associated with achievement of EMR. As dasatinib is a novel, oral tyrosine kinase inhibitor with improved potency, identification of very early molecular response (VEMR) would be beneficial.
Aims
We evaluated the possibility of the VEMR at 1 month predicting long-term outcomes in newly diagnosed CP-CML patients treated with dasatinib.
Methods
In this multi-center, observational, open-label study, 102 patients with CP-CML were enrolled to receive dasatinib at a dose of 100 mg once daily. The primary end point was complete molecular response (CMR) by 18 months. Secondary end points including molecular response (MR) by 1, 3, 6, 12, 18, 24, 36 months, time to and duration of MMR and CMR, and safety were tested. A receiver operating characteristic (ROC) curve from BCR-ABL1 transcript level on Day+28 was calculated to predict EMR and MMR at specific timepoints.
Results
Median age was 49 years (19-81 years) and 61 patients were male. With median follow-up duration of 33.6 months (0.9-38.6 months), 71 (69.6%) out of 102 patients were still on dasatinib treatment and 31 patients discontinued due to disease progression (n=2) or treatment failure (n=3) or adverse events (n=18) or other reasons (n=8). The BCR-ABL1 mutations, assessed in 10 patients after dasatinib discontinuation, were detected in 3 patients which were all T315I mutation. The cumulative CMR by 18 months and MMR by 36 months were 20.5% and 84.8% respectively. In safety analyses, grade 3/4 thrombocytopenia (30.3%) was most common. Pleural effusion occurred in sixteen (15.6%) patients which were mostly grade 1/2. The cut-off value of BCR-ABL1 transcript on Day+28 was 40% by ROC curve analysis. Among 95 patients who had available molecular data of both D+28 and 12 months, fifty nine (62.1%) patients had less than 40% of BCR-ABL1 transcript (VEMR) on Day+28. Among them, 49 (83.1%) patients achieved MMR at 12 months. However, only 27.8% (10 out of 36 patients) of patients without VEMR achieved MMR (p<0.0001). Among 72 patients who had available molecular data of both D+28 and 36 months, forty-six (63.9%) patients achieved VEMR. In 46 VEMR patients, 43 (93.5%) patients achieved MMR at 36 months. However, 80.8% (21 out of 26 patients) of patients without VEMR achieved MMR (p=0.10). Three-year overall survival (OS) & progression-free survival (PFS) rates were 98.0% and 95.1%, respectively. Three-year PFS rates for VEMR and no VEMR group were 98.4% vs. 88.8% respectively (p=0.04).
Conclusion
Our study shows that VEMR at 1 month can be a strong predictor for further molecular responses as well as long-term outcome. Therefore, it would be helpful to monitor BCR-ABL1 transcript level at 1 month in patients who treated with more potent TKIs.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, Molecular response, prognosis, Tyrosine kinase inhibitor