HyperCKemia in CML Patients on Imatinib Mesylate.

Imatinib mesylate (IM) is the standard therapy for Philadelphia chromosome positive chronic myelogenous leukemia (CML). It is generally well tolerated with most non-hematologic toxicities being mild to moderate in severity. Muscle cramps and/or myalgia may occur in up to half of patients (pts) treated, particularly with doses of IM > 400 mg/day. Prompted by a case of rhabdomyolysis, we began to monitor creatine kinase (CK) levels in CML patients on IM in 2005. 71 patients with chronic phase CML (diagnosed between 1994 and 2007 and treated with IM between 2000 and 2007) had CK levels done every 3 months. Elevated CK occurred in 33/71 (47%) of patients (30% grade 1; 11% grade 2; 4% grade 3 and 2% grade 4); the majority (91%) (including those with ≥ grade 3 toxicity) were taking ≤ 400 mg/day of IM. Of these 33 patients, 21 had a normal baseline CK. The mean and median duration of IM exposure at the time of first documented CK elevation in these 21 patients was 82.5 weeks and 53 weeks respectively (range 4 – 300 weeks). 36% (12/33) of the patients with elevated CK levels reported associated symptoms (muscle cramps, muscle spasms and/or myalgia): the majority of the adverse events were ≤ grade 2 in severity, with some pts reporting more than 1 symptom. CK elevation was documented once in 8 patients, continuously in 9 patients and intermittently in 16 patients. 7 patients required dose modification; all subsequently had a reduction in CK levels to ≤ grade 1. Of the 38/71 who had normal CK levels, 24% (9/38) reported either grade 1 or 2 muscle cramps and/or myalgia: only 1 of these pts required dose reduction due to muscle related toxicity. Possible factors contributing to CK elevation included hypothyroidism (9 pts), vigorous physical activity (7 pts), antipsychotics (7 pts), cholesterol lowering agents (6 pts), alcohol use (2 pts), beta blockers and infection (1 pt each).

Conclusions:

1. hyperCKemia is common in patients on IM for CML (1);

2. hyperCKemia is not correlated with myalgia or muscle cramps;

3. many patients had multiple potential etiologies for increased serum CK;

4. hyperCKemia responds to IM dose modification.