TKI Discontinuation and Chronic Myeloid Leukemia

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TKIs offer the possibility of durable responses for patients with CML, though it is unclear whether discontinuation is feasible.
TKIs offer the possibility of durable responses for patients with CML, though it is unclear whether discontinuation is feasible.

Tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML) can yield impressive survival rates among those patients who achieve sustained bone-marrow complete cytogenetic response (CCyR).1 These patients now have an expected survival rate “comparable to that of the general population,” experts noted.1

Current clinical practice involves lifelong continuation of TKI therapy, which tends to be well-tolerated overall.2 But lifelong TKI therapy can become a financial burden for some patients; TKIs can also preclude the possibility of pregnancy.

Clinical studies tend to focus on grade 3 and 4 toxicities—adverse events that can be severe enough to prompt discontinuation.  But in the setting of lifelong TKI therapy, even low-grade side effects can become important concerns.

For some patients, furthermore, long-term TKI therapy can cause late endocrine, cardiovascular, pulmonary, and gastrointestinal toxicities, as well as myalgia, rash, peripheral edema, or musculoskeletal symptoms.3

Increasingly, patients are approaching their oncologists about the possibility of TKI discontinuation after CCyR. 4 Patient concerns and health care cost considerations have prompted research into the possibility of sustained treatment-free remission for some patients.

RELATED: Adding Pioglitazone to Imatinib May Improve Response Rate in CML

The depth of clinical response is determined using hematologic and cytogenetic assessments. CCyR involves the absence of Philadelphia chromosome-positive (Ph+) cells; molecular responses are measured with reverse-transcriptase PCR from marrow or blood samples, typically as the ratio of BCR-ABL1 to ABL transcripts (log-scale BCR-ABL1 percentage).

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