Contributions
Abstract: PB1822
Type: Publication Only
Background
Several types of transcripts can be produced during chromosomal translocation, which lead to formation of the BCR/ABL fusion gene in patients with chronic myeloid leukemia (CML). Previous results of a few large studies showed that patients with CML in chronic phase (CP) with e13a2 transcript have inferior responses to frontline imatinib therapy compared to patients with the e14a2 transcript.
Aims
To investigate the prognostic significance of e13a2 and b14a2 BCR/ABL1 transcripts in CML patients switched to nilotinib after suboptimal response or failure on frontline imatinib.
Methods
CP-CML patients (N=143) who did not achieve complete cytogenetic response (CCR) after imatinib therapy (600 or 800 mg once daily) and were switched to nilotinib 400 mg twice daily, were enrolled in present study (55 patients with e13a2 transcript and 88 patients – with e14a2 transcript). The median of imatinib treatment before switching to nilotinib was 44 months (range 1-137). A qualitative RT-PCR for BCR/ABL1 transcript was performed at diagnosis. The patients who achieved CCR but did not have major molecular response (MMR) as well as patients with rare BCR/ABL1 transcripts and coexpression were excluded from the analysis. Probability of overall survival (OS), progression-free survival (PFS) and event-free survival (EFS) were calculated using Kaplan-Meier method. Event in EFS was defined as death of a patient on treatment for any reason, progression of disease, or loss of CCR or MMR. Differences between groups were assessed using log-rank, χ2-tests and Mann-Whitney U-tests. Cumulative probability of CCR, MMR, MR4,0 (BCR/ABL<0,01 %) and loss of CCR and MMR was assessed using Kaplan-Meier method.
Results
The median follow up was 23 (range 4 – 82) months. The groups with both of the BCR/ABL1 main transcripts were comparable for the disease phase, Sokal risk score and the proportion of patients with additional chromosomal abnormalities in Ph-positive cells. No correlation of transcript type with age or sex was observed. Transcript e13a2 was associated with higher WBC (120x109/L vs. 95.3x109/L, p=0.02) and lower baseline percentage of eosinophils (p=0.041). No differences were found in other differential counts of peripheral blood, hemoglobin concentration, or spleen size.
Conclusion
Analisys of 143 CML patients treated with nilotinib as the 2-nd line therapy suggests that patients with e13a2 transcript have less stable therapy response and demonstrate higher cumulative incidence of MMR loss (molecular relapse). But outcome differences were nor observed. Further analysis of a larger number of events and longer observation is required.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, BCR-ABL, Molecular relapse, Cytogenetics
Abstract: PB1822
Type: Publication Only
Background
Several types of transcripts can be produced during chromosomal translocation, which lead to formation of the BCR/ABL fusion gene in patients with chronic myeloid leukemia (CML). Previous results of a few large studies showed that patients with CML in chronic phase (CP) with e13a2 transcript have inferior responses to frontline imatinib therapy compared to patients with the e14a2 transcript.
Aims
To investigate the prognostic significance of e13a2 and b14a2 BCR/ABL1 transcripts in CML patients switched to nilotinib after suboptimal response or failure on frontline imatinib.
Methods
CP-CML patients (N=143) who did not achieve complete cytogenetic response (CCR) after imatinib therapy (600 or 800 mg once daily) and were switched to nilotinib 400 mg twice daily, were enrolled in present study (55 patients with e13a2 transcript and 88 patients – with e14a2 transcript). The median of imatinib treatment before switching to nilotinib was 44 months (range 1-137). A qualitative RT-PCR for BCR/ABL1 transcript was performed at diagnosis. The patients who achieved CCR but did not have major molecular response (MMR) as well as patients with rare BCR/ABL1 transcripts and coexpression were excluded from the analysis. Probability of overall survival (OS), progression-free survival (PFS) and event-free survival (EFS) were calculated using Kaplan-Meier method. Event in EFS was defined as death of a patient on treatment for any reason, progression of disease, or loss of CCR or MMR. Differences between groups were assessed using log-rank, χ2-tests and Mann-Whitney U-tests. Cumulative probability of CCR, MMR, MR4,0 (BCR/ABL<0,01 %) and loss of CCR and MMR was assessed using Kaplan-Meier method.
Results
The median follow up was 23 (range 4 – 82) months. The groups with both of the BCR/ABL1 main transcripts were comparable for the disease phase, Sokal risk score and the proportion of patients with additional chromosomal abnormalities in Ph-positive cells. No correlation of transcript type with age or sex was observed. Transcript e13a2 was associated with higher WBC (120x109/L vs. 95.3x109/L, p=0.02) and lower baseline percentage of eosinophils (p=0.041). No differences were found in other differential counts of peripheral blood, hemoglobin concentration, or spleen size.
Conclusion
Analisys of 143 CML patients treated with nilotinib as the 2-nd line therapy suggests that patients with e13a2 transcript have less stable therapy response and demonstrate higher cumulative incidence of MMR loss (molecular relapse). But outcome differences were nor observed. Further analysis of a larger number of events and longer observation is required.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, BCR-ABL, Molecular relapse, Cytogenetics