Chronic myeloid leukemia (CML) is caused by formation of the BCR-ABL1 fusion protein. Tyrosine kinase inhibitors (TKI) that target BCR-ABL1 are now the standard of care for patients with CML. Molecular monitoring of residual BCR-ABL1 mRNA transcripts, typically performed using real-time quantitative PCR, has improved treatment management, particularly for patients with CML in chronic phase. Major molecular response (MMR; i.e., a ≥3-log reduction in BCR-ABL1 transcript levels) is used in current treatment guidelines to assess prognosis. Recent evidence suggests that deeper molecular responses (≥4-log reductions in BCR-ABL1 transcript levels), particularly when attained early during treatment, may have even better correlation with long-term outcomes, including survival and disease progression. Furthermore, achieving deep molecular response is a requirement for entering trials evaluating treatment-free remission (TFR). In this review, we discuss the evolving definition of minimal residual disease and the various levels of molecular response under evaluation in current clinical studies. In addition, the available clinical data on achieving MMR and deeper levels of molecular response with TKI therapy, the prognostic value of deep molecular response, and factors that may predict a patient's ability to achieve and sustain a deep molecular response on TKI therapy are also discussed. Available data from TFR studies are addressed. We discuss current knowledge of the ideal conditions for attempting treatment discontinuation, factors predictive of molecular relapse, when TKI therapy should be restarted, and which therapeutic strategies (when administered in the first-line setting and beyond) are expected to best enable successful TFR.
©2013 AACR.