TKI Discontinuation and Chronic Myeloid Leukemia

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.

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).