How complete is “complete” molecular response in imatinib-treated chronic myeloid leukemia?

Authors: David M. Ross a; Timothy P. Hughes

Elsewhere in this issue of the journal Verma and colleagues 1 report a case in which a complete molecular response (CMR) induced by imatinib treatment was sustained for at least 2 years after cessation of imatinib. Imatinib mesylate is a highly effective treatment for chronic phase chronic myeloid leukemia. With increasing duration of imatinib therapy there is a progressive reduction in BCR-ABL levels measured by real-time reverse transcriptase Q-PCR. Some patients will have undetectable BCR-ABL using sensitive reverse transcriptase PCR methods. Sustained undetectable BCR-ABL using RT-PCR with a sensitivity of at least 4.5-log below the pre-treatment BCR-ABL level is often referred to as CMR. The probability of CMR on imatinib therapy is very low in the first 2-3 years of treatment, but thereafter there is ongoing recruitment of patients to CMR so that around 40-50% of first-line imatinib-treated patients will have undetectable BCR-ABL mRNA after 5 years on treatment 2. Assuming a leukemic burden of 1012 cells at diagnosis, CMR could be associated with a variable burden of residual disease ranging from zero to more than 106 CML cells. With increasing numbers of CML patients in this category we need a better understanding of the biology and prognosis of imatinib-induced CMR.

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