VERY ELDERLY CP-CML PATIENTS TREATED WITH IMATINIB FRONTLINE: HAVE CONCOMITANT THERAPIES AN IMPACT ON OUTCOME AND TOXICITY?

With the introduction of tyrosine-kinase inhibitors (TKIs) the expected survival of CML patients is approaching that of the general healthy population, so that a large number of CML patients are elderly or very elderly. However, the latter are frequently not eligible for clinical trials. Imatinib is effective even in this setting despite of concomitant therapies that may more frequently require dose reductions, as well as pharmacologic adjustments, to avoid drug interactions. We wanted to assess if and which concomitant drugs have an impact on both outcome and hematologic and extra-hematologic toxicity in CP-CML very elderly patients (age >75 years). Two hundred and two very elderly CP-CML patients treated with imatinib frontline were retrospectively evaluated using data collected from 31 Italian Institutions. Median age at imatinib start was 78.7 years (range 75-93); 109 (54.0%) were male. According to the Sokal Scoring System, 60 patients (29.7%) were high risk. Sixty-four (31.7%) were treated with reduced dose imatinib (<400 mg/day), and the remaining patients with imatinib >400 mg/day. Complete cytogenetic response (CCyR) was obtained in 33 (16.3%) patients within 12 months and in 85 (42.1%) after 12 months. Concomitant drugs were 1-2 in 76 (37.6%) patients, 3-4 in 56 (27.7%), and >5 in 41 (20.3%); 29 (14.4%) did not assume any concomitant medications. Antihypertensive drugs and PPIs were the most frequent therapies associated with imatinib in our population. Thus, we focused on the effects of these two classes of drugs. We did not find any significant correlation between antihypertensive drugs and CCyR rate (p=0.50), nor with grade 3-4 hematologic and extra-hematologic toxicities (p=0.28 and 0.34, respectively). Similarly, PPIs did not correlate neither with outcome (p=0.33), nor with hematologic or extra-hematologic toxicities (p=0.33 and 0.59, respectively). However, in this preliminary analyses, considering antihypertensive classes, CCyR was obtained later in patients assuming b-blockers (p=0.017), while angiotensin II receptor blockers showed a trend toward a significant association (p=0.056). Our preliminary results confirm the well-known safety and efficacy of imatinib also in very elderly patients who frequently take other medications. Further analyses will be done to investigate single classes of concomitant drugs as predictors of outcome or toxicities to help clinician selection of the most appropriate combination therapies