Adherence to Imatinib Mesylate Treatment: Two Years Follow up
Authors: Doti Carlos A. , Stemmelin German R , Moiraghi Elena Beatriz , Flores María Gabriela , Garcia Juan , Murro Hector , Bullorsky Eduardo O 
Published: April 2020

Abstract
Background: Since the introduction of Imatinib (IM), the treatment of chronic myeloid leukemia (CML) experienced its most important change. As this drug became the first line for the treatment of CML, we learned that under-dosing was associated with a delay in achieving cytogenetic response and the development of acquired resistance. Last year we presented a case-control study that analyzed how compliance affects the cytogenetic response to Imatinib. This is an update of that data.
Materials and Methods: Twenty-four patients with newly diagnosed Ph (+) chronic phase CML (CP-CML) were included and followed for 24 months. Patients received 400mg of IM and were asked to note down all taken doses, and reasons for non-compliance. Follow up visits were scheduled every 28–30 days and prescriptions were filled in order to last for only 30 days. During each visit, the medication was counted and non-adherence reasons were determined. Adverse events were graded according to the CTC and modifications in the Imatinib dose were only allowed with related adverse events with a CTC score ≥3.
As a control group, we matched each case with a Phi + CP-CML patient from our data base of the same sex and similar age as the case patient. All control patients had to have complete information about dosing and response. They all received initial treatment with IM 400mg; thereafter, dose was adjusted according to each physician’s criteria. Compliance was measured as: mg prescribed/mg taken during the study period.
Results: Twenty-four patients, 14 males median age 56 yo (range: 24–83), were included in the study. Three were lost to follow up, leaving only twenty-one for analysis of compliance. At the end of the first year, all patients had complete hematological response. Compliance during these 12 months was 96.1, which is clearly superior to the 80% reported in the setting of clinical trials. All patients had a complete hematological response, 89.9 achieved a major cytogenetic response (MCyR) and 87.4 a complete cytogenetic response (CCyR), compared to 60 of the control group with a MCyR (p=0.027) and 57.8 a CCyR (p=0.025). During the second year, four patients lost CCyR, three responded to an increase in IM dose and one progressed to an accelerated phase and died. Compliance fell slightly during this period to 90.86% which was reflected in 81.66% CCyR, which was still statistically higher than the 54% of major responses in the control group (p=0.033). In both groups, none of the patients not achieving MCyR at 12 months achieved MCyR at 24 months. Hematological toxicity was more frequently observed within the first 6 months of treatment and after the increase in dosage. Severity and incidence of adverse events were similar in both groups, and were the main reasons for interruption or reduction of IM dose in the control group. The only additional difference besides compliance between the two groups was the average IM dose prescribed during the duration of the study (cases group: 430mg – control group: 330mg).
Conclusions: Adherence to Imatinib is associated with an improvement in cytogenetic response that can be seen even at two years after the start of therapy. Since outcome and development of resistance seem to be associated with compliance to therapy, emphasis should be put on maintaining treatment at an adequate dose for as long as possible.