In the 1990s, the introduction of the tyrosine kinase inhibitor (TKI) imatinib for BCR-ABL-positive, chronic phase chronic myeloid leukemia (cpCML) drastically changed treatment and outcomes for patients with the disease.1 Instead of needing hematopoietic stem cell transplantation, these patients can now have their cpCML managed as a chronic disease and, indeed, they now have overall survival similar to that of age-matched controls.2 For example, the longest surviving patient with CML has been taking imatinib for over 24 years.3
Over time, many patients with cpCML achieve deep molecular responses. Furthermore, daily TKI treatment is often accompanied by side effects, can affect family planning for younger patients, and may be financially burdensome.4 Because of this, researchers have started to evaluate the discontinuation of TKIs in patients who have sustained DMRs.1
In an editorial published in Haematologica, Charles Schiffer, MD, the Joseph Dresner Chair for Hematologic Malignancies in the departments of oncology and medicine at Wayne State University School of Medicine and the Karmanos Cancer Institute in Detroit, Michigan, summarized the eligibility criteria for and outcomes of recent clinical trials on TKI discontinuation.1
Although each TKI discontinuation study conducted thus far has had slightly different eligibility criteria, Dr Schiffer created a “consensus approximation.” Patients must have had (1) TKI treatment for at least 3 years and (2) a continuous deep molecular response for at least 2 years (minimum of MR4 or MR4.5).1
“The process is quite simply that you stop [the TKI treatment] and then monitor for the possibility of recurrence with blood tests,” explained Dr Schiffer in an interview with Hematology Advisor.
To monitor recurrence, the health care provider must conduct quantitative polymerase chain reaction (qPCR) capable of detecting at least MR4.5 every 4 to 6 weeks for 6 to 8 months. Then, the qPCR monitoring may be relaxed to every 2 months for 1 year and subsequently every 3 months for at least 3 years.1