Assessment of long-term toxicities of imatinib in CML: Experience from a tertiary care cancer centre in south India.

Abstract

6564 Background: Imatinib has been the standard 1 st line drug for chronic myeloid leukemia (CML) in chronic phase for decades. Literature is replete with data regarding acute toxicities of imatinib, but chronic long-term effects of the drug on cardiac, renal, endocrine, skin and bone health are less explored. In rare cases, imatinib has been postulated to cause left ventricular dysfunction, impairment in bone mineral density, thyroid hormone abnormalities and sensorineural hearing loss. Methods: We conducted a prospective study on CML patients aged 18 and above who had taken Imatinib for a minimum duration of 10 years. All patients were subjected to a detailed skin examination, laboratory tests including complete blood count, liver/renal function tests, thyroid profile, 2D echo, bone densitometry and pure tone audiometry. All tests were organized in accordance with a camp conducted for CML patients in our center. Children, pregnant women, patients who had not achieved major molecular remission and patients in accelerated phase/blast crisis were excluded. Results: 100 patients (males n=60, females, n=40) participated in the study. Median age was 45years (IQR 30-60). All patients were in major molecular remission with excellent drug compliance. Regarding the rarer side effects, 2D echo revealed left ventricular dysfunction in 4 patients (4%, n=1 moderate, n=3 mild). After interruption of drug, ejection fraction improved in all 3 patients with mild LV dysfunction (repeat 2d echo after 3 months). Pure tone audiometry revealed bilateral sensorineural hearing loss in 5 patients (5%, moderate n=3, severe n=2). Repeat testing done after 3 months post drug discontinuation showed improvement for 2 out of 3 patients with moderate sensorineural hearing loss (conversion to mild degree). 10 patients had osteopenia and 2 patients had osteoporosis in bone densitometry scans. Drug was not discontinued for the same. Patients were started on calcium+ vitamin D supplementation for osteopenia and 6 monthly zoledronic acid injections for osteoporosis. Cutaneous side effects were reported in 43%(N=43). Hyperpigmentation was the most common, seen in 30%(n=30) followed by hypopigmentation in 11% and chronic malar flush in 2%. Menstrual irregularities were reported in 10 females (n=10, 25%), most common being oligomenorrhea(n=7). 4 males (6.66%) had gynecomastia on examination. Anemia was seen in 25% (n=25,10 males and 15 females). Hypophosphatemia and elevated TSH were seen in 12 (12%) and 7 patients (7%) respectively. Conclusions: CML is now equated to a chronic disease with patients attaining a near normal life expectancy which makes it very important for clinicians to be well versed with both acute and chronic toxicities of imatinib. Through our study, we were able to highlight certain rare toxicities like ejection fraction abnormalities, hearing loss and bone mineral density changes that may be seen with imatinib.