PB1929 POTENTIAL DRUG-DRUG INTERACTIONS AMONG PATIENTS WITH CHRONIC MYELOID LEUKEMIA UNDER TYROSINE KINASE INHIBITOR THERAPY WITH IMATINIB
Authors: A. Kunbaz, A.E. Eskazan, D. Ozmen, A. Sasmaz, A. Hakmi, S. Shahab, T. Elverdi, A. Salihoglu, M.C. Ar, T. Soysal
Journal: HemaSphere (2019)

Background: The introduction of imatinib (IM) has revolutionized the treatment of chronic myeloid leukemia (CML). CML patients (pts) achieving optimal responses (ORs) under tyrosine kinase inhibitor (TKI) therapy would expect to have similar life expectancies of normal population. During long-term TKI treatment, co-medications administered due to comorbidities may lead to potential drug-drug interactions (DDIs) between TKIs and these drugs. DDIs can be problematic in clinical practice both in terms of generation of TKI toxicities and lack of achieving ORs. Aims: We aim to investigate the possible DDIs between TKIs and the concurrent drugs used in CML pts and their impact on the generation of adverse events (AEs) of TKIs and on achieving ORs under IM therapy. Methods: We retrospectively evaluated CML pts in chronic phase. Demographic and clinical data including disease risk scores, TKI responses and AEs were collected from the medical records. Charlson comorbidity index (CCI) of each patientat diagnosis was calculated as stated before [Blood. 2015;126(1):42-9]. We included pts who had a follow-up ≥12 months and with available data on concurrent medications that were used with IM ≥1 month. Drugs which were taken with IM only were included in the DDI analysis. Information regarding possible DDIs between IM and the other drugs were gathered from [Blood. 2011;117(8):75-87] and Mobile Drug Guide (http://mdg.usgovxml.com/). Results: A total number of 118 pts were included (Table 1). There were 69 pts (58%) with at least one medication concurrently used with IM (Group A), whereas 49 patients (42%) only received IM (Group B). Median age was higher in Group A than that of Group B (p = 0.079). The percent of male pts in Group B was significantly higher than Group A (p = 0.006). Two groups were comparable for Sokal risk and CCI scores. Median durations of IM use and entire follow-up were significantly longer in Group A than those of Group B (80 months vs. 56 months, p = 0.007 and 89 months vs. 70 months, p = 0.028, respectively). Although not statistically significant, the cumulative major molecular response (MMR) rates under IM were higher in Group A. There were significantly more pts in Group A experiencing AEs than that in Group B (41 (59%) vs. 20 (41%), p = 0.047). The number of pts in both groups who required an IM dose modification or a switch to second-generation TKI (2GTKI) were equally balanced (Table 1). After a median follow-up of 82.5 months, there were 13 patients who died or were lost to follow-up. The total number of concurrent drugs were 110 at diagnosis, and 119 at the last follow-up.Throughout the follow-up, the most prescribed drugs were anti-hypertensive drugs (37.7%), antidiabetic drugs (12.2%), levothyroxine (6.1%) and proton-pump inhibitors (4.3%). Regarding DDI analysis, after excluding pts receiving drugs with potential DDI under 2GTKI (n = 2), we further divided Group A into two as pts receiving concurrent drugs with/without potential DDIs (Table 2). When we compared these two subgroups with each other, they were equally balanced regarding the number of pts with AEs, the number of cases who needed IM dose reduction/elevation, molecular responses and pts with a TKI switch.Summary/Conclusion: The life expectancy of CML pts with ORs under TKI therapy approaches that of the general population. As the CML population ages, pts with CML receive concurrent drugs due to comorbidities, which might have potential DDIs with TKIs. While managing CML, physicians should be aware of these DDIs, which might potentially have an impact on the efficacy and toxicity of TKIs.