Age Influences Initial Dose and Compliance to Imatinib In Chronic Myeloid Leukemia Elederly Patients but Concomitant Comorbidities Appear to Influence Overall and Event-Free Survival

Comorbidities have been identified as significant determinants of response to therapy in elderly patients with acute myeloid leukemia, breast cancer, head and neck, and lung cancer. Charlson comorbidity index (CCI) is a list of comorbidities with a weight assigned from 1 to 6 derived from relative risk estimates of a proportional hazard regression model using clinical data. We applied CCI stratification on a large cohort of chronic myeloid leukemia (CML) very elderly patients (> 75 years) treated with imatinib, in order to observe the impact of concomitant diseases on both compliance and outcome. One hundred and eighty-one patients were recruited by 21 Italian centers. There were 95 males and 86 females, median age 78.6 years (range 75–93.6). According to Sokal score, 106 patients were classified as intermediate risk and 55 as high risk (not determined in 20 patients). According to CCI stratification, 71 patients were score 0, 50 patients had a score 1, 37 patients had score 2 and 23 patients had score ≥ 3. Imatinib standard dose was reduced in 68 patients independently from the evaluation of baseline comorbidities but based only on physician judgement: 43.6% of patients with score 0 started with a reduced dose (200–300 mg/day) compared to more than 50% of patients with score ≥ 3. No significant differences were found in terms of further reduction of the dose (39% in patients with score 0 compared to 21% in patients with score ≥ 3) or in terms of discontinuation due to toxicity (58% in patients with score 0 vs 48% in patients with score ≥ 3). We did not find significant differences as regards the occurrence of hematologic side effects, probably due to the initial reduction of the dose: 39% of patients with score 0 experienced grade 3/4 hematologic toxicity (most commonly anemia) compared to 35% of patients with score ≥ 3. Independently from the initial dose, comorbidities again did not have an impact on development of grade 3/4 non-hematologic side effects (most common skin rash, muscle cramps and fluid retention): 62% of patients with score 0 compared to 35% of patients with score ≥ 3. Notwithstanding the reduced dose and the weight of comorbidities we did not find differences in terms of efficacy: 66% of patients with score 0 achieved a CCyR compared to 56.5% of patients with score ≥ 3. Comorbidities appeared to have an impact on EFS (34 months for patients with score 0 vs 23.5 months for patients with score ≥ 3) and influenced the median OS (40.8 months for patients with score 0 vs 10.6 months for patients with score ≥ 3). Our results suggested that treatment of very elderly CML patients might be influenced by personal physician perception: evaluation at baseline of comorbidities according to CCI should improve initial decision-making in this subset of patients