Deep molecular response predicts survival in CML

New research has shown that a majority of patients with chronic myeloid leukaemia (CML) who are treated with the tyrosine kinase inhibitor imatinib can achieve a deep molecular response (≥4.5-log reduction in BCR–ABL fusion gene transcript levels; MR^4.5) and that MR^4.5 is predictive of survival.

Major molecular response (MMR; ≥3-log reduction in BCR–ABL transcript levels) is currently used to assess prognosis. However, mounting evidence has shown that deeper molecular responses (that is, MR^4.5 or higher) might correlate better with long-term outcomes. The CML–Study IV trial is the first to evaluate correlations between MR^4.5 and long-term outcomes; molecular monitoring was performed for all patients in the study from the beginning.

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More than 1,500 patients were enrolled and were assigned to several different imatinib-based regimens in terms of dosing or combination with other therapies (namely, IFN-α, cytarabine or alone). The median observation time was 67.5 months.

“Deep molecular response is a prestage of cure of CML,” explains lead investigator Rüdiger Hehlmann, from the University of Heidelberg, Germany. “We found that a deep response level can be achieved in the majority of imatinib-treated patients with CML.” Indeed, after 9 years, 70% of patients achieved MR^4.5. Furthermore, this level of response was more common in patients who were treated with the highest doses of imatinib (800 mg per day, tolerability-optimized). “It is also interesting that MR^4.5 is achieved faster in these patients than those receiving 400 mg imatinib,” comments Hehlmann. Additionally, MR^4.5 at 4 years independently predicted survival and, in turn, high-dose imatinib and early MMR predicted MR^4.5.

These results suggest that MR^4.5 can be used to guide treatment cessation in patients with CML, with treatments selected that can achieve an early deep molecular response.