Combining BCR-ABL1 transcript levels at 3 and 6 months in chronic myeloid leukemia: implications for early intervention strategies

Abstract

Several groups have shown that that the BCR-ABL1 transcript level measured at 3 or 6 months after starting treatment with tyrosine kinase inhibitors strongly predicts clinical outcomes for patients with chronic myeloid leukemia. In this work, we asked whether the prognostic value of the 3-month transcript level could be improved by combining the 3- and 6-month results. We classified patients treated with imatinib and patients treated with dasatinib according to their transcript levels at 3 months and 6 months. The patients who met the 3-month landmark but failed the 6-month one had outcomes identical to those of patients who met both landmarks, whereas the patients who failed the first landmark but met the second one had prognoses similar to those who failed both landmarks. In summary, early intervention strategies can be based robustly just on the transcript level at 3 months. This trial was registered at www.clinicaltrials.gov as # NCT01460693.

Conflict of interest statement

Conflict-of-interest disclosure: D. Marin, D. Milojkovic, S.O., and J.G. received research support from Novartis and Bristol Myers-Squibb. The remaining authors declare no competing financial interests.

Figures

Figure 1

OS, CI of CCyR, and CI of CMR according to the BCR-ABL1 transcript level at 3 and 6 months. (A) The 8-year probability of OS. The 181 (66%) imatinib-treated patients with low transcript numbers both at 3 months (<9.8%) and at 6 months (<1.67%) had an OS of 93.5% and constitute the reference category for this analysis (group A). The 57 patients (21%) who had high transcript levels on both occasions (group B) had an OS of 55.6% (P < .001). The 30 patients (11%) with low transcript levels at 3 months but high transcript levels at 6 months (group C) had an OS of 92.4% (P = .78). The 6 patients (2%) who had high transcript levels at 3 months but low levels at 6 months (group D) had OS= 83.3% (P = .23). The P value for the comparisons between groups B and C was P = .004 and between groups B and D was P = .39. Similar results were found when we used PFS as outcome criterion; namely, the PFS for patients in the group A was 93.0%. Group B patients had a PFS of 52.5% (P < .001). Group C patients had a PFS of 92.4% (P = .72) and group D patients had a PFS of 83.3% (P = .31). The P value for the comparisons between groups B and C was .001 and between groups B and D was .26. (B) The 8-year CI of CCyR. The 8-year CI of CCyR for patients in groups A, B, C, and D (defined above) was 100%, 14.9% (P < .001), 99.5% (P = .001), and 33.3% (P < .001). The P value for the comparison between groups B and C was <.001 and between groups B and D was .09. (C) The 8-year CI of CMR. We classified the imatinib-treated patients according to whether the transcript level at 3 and 6 months was higher or lower than the previously reported cut off that optimally predicts for this outcome (0.61% for 3 months and 0.21% for 6 months). A total of 34 patients(13%) had low transcripts both at 3 and 6 months, and their 8-year CI of CMR was 75.5%. The CI of CMR for the 6 patients (2%) who had low transcript levels at 3 months but high levels at 6 months was 100% (P = .8). The 193 (70.5%) patients who had high transcript levels on both occasions had a CI of CMR of 1.25% (P < .001) and the 40 (14.5%) patients who had high transcript levels at 3 months but low levels at 6 months had a CI of CMR of 3.6% (P < .001).