Clinical Relevance of Failure to Achieve Early Molecular Response in Chronic Myeloid Leukemia in Chronic Phase

Purpose

The early molecular response (EMR, ≤ 10% BCR-ABL1 at 3 months) of tyrosine kinase inhibitor (TKI) treatment for patients with chronic myeloid leukemia (CML) in chronic phase (CP) has been reported to have strong correlation with long-term outcome. We aim to investigate the prognostic interaction of the EMR and major molecular response (MMR).

Methods

We retrospectively reviewed data for a total of 165 patients with newly diagnosed CML-CP who received TKIs (imatinib, nilotinib, or dasatinib) as first-line treatment between January 2003 and April 2013. Of the total 128 patients who were regularly monitored by peripheral blood molecular analysis, 85 had a BCR-ABL1 assessment at 3 months and were finally included in the analysis.

Results

The median age of all patients was 49 years and 87.1% received imatinib as first line treatment. High risk group by Sokal and EUTOS were 29.4% and 14.1%, respectively. Patients with EMR (n = 56, 65.9%) had a tendency to have low risk disease and to be treated with 2^nd generation of TKIs. With a median follow-up duration of 53.6 months (range, 5.4-131.3), the 5-year OS, 5-year FFS, and 5-year EFS were 92.5%, 74.8%, and 68.0%, respectively. Median time to achieve MMR was 11.1 months (95%CI, 8.4 - 13.8). The outcomes at 5 year comparing patients whose BCR-ABL1 transcript levels ≤ 10% vs >10% at 3 months were as follows: OS, 92.2% (95% CI 84.9-99.1) vs 92.8% (95% CI 83.7-102.3), p = 0.819; FFS, 84.7% (95% CI, 75.6-94.4) vs 57.4% (95% CI, 39.0-75.0), p < 0.001; and EFS, 73.6% (95% CI 62.5-85.5) vs 57.8% (95% CI 40.0-76.0), p = 0.050. Six (10.7%) of 56 patients with BCR-ABL1 transcript levels ≤ 10% at 3 months failed to achieved an MMR and 18 (62.1%) of 29 patients with > 10% at 3 months achieved an MMR. Based on these heterogeneous clinical outcomes, we further explored subgroup analysis according to the achievement of MMR for refined discrimination of survival outcomes. There was no significant difference of clinical outcomes between ≤ 10% vs > 10% at 3 months among the patients who achieved MMR (OS, p = 0.376; FFS, p = 0.793; and EFS, p = 0.266). In patients who did not achieved MMR, only FFS was significantly difference between ≤ 10% vs > 10% at 3 months (OS, p = 0.489; FFS, p = 0.014; and EFS, p = 0.199).

Conclusion

Patients who failed to achieve EMR but finally reached MMR have excellent prognosis that whether we have to change TKI for EMR failure is to be addressed by ongoing prospective clinical trials.