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adherence. This study by Marin et al. in patients with chronic myeloid leukemia found that 26% of patients were non-adherent with their treatment, while in the present study, 22% were non-adherent to cytoreduction and 29% to either cytoreduction or antithrombotic drugs. Furthermore, our questionnaire provided insight into the reasons why the patients missed taking their drugs.
The causes for non-adherence were also approached in chronic myeloid leukemia by Marin et al. who reported younger age as a major factor.6 Likewise, in acute lym- phoblastic leukemia, Bhatia et al. found that adherence to maintenance therapy was suboptimal in teenagers among whom the non-adherence rate was 20.5%.9 This study also pointed to socio-economic conditions as a major determinant of adherence. In our study, factors significant- ly associated with non-adherence were found mostly in patients who took their treatment orally, and included younger age, choosing the pill intake schedule themselves, dispersing their intake through the day and a small num- ber of different drugs to take (Table 2). This indicates that, in addition to personal traits (age, ethnic, socio-economic background), the way of managing patients’ drug intake (route of administration, time of the day, number of differ- ent treatments) has an impact on adherence. Interestingly, patients receiving subcutaneously injected cytoreduction showed poorer adherence to oral antithrombotic drugs than patients receiving oral cytoreduction. Together with the fact that treatment adherent patients were more likely to be taking several drugs and the fact that diabetic patients showed a higher rate of adherence to treatment, this suggests that having a higher number of oral drugs to take makes it less likely to miss one intake. Physicians should therefore probably put even more effort into help- ing patients being treated with subcutaneous cytoreduc- tion ensure good adherence to their antithrombotic drug treatment. Unexpectedly, the occurrence of adverse effects to the drugs was not reported by patients as a determining factor in their non-adherence. We also observed that hav- ing suffered a complication and/or phenotypic evolution of the disease did not increase adherence to treatment. This is coherent with the fact that most non-adherent patients reported not believing that non-adherence may affect the clinical outcome of their disease. These ele-
ments suggest that good comprehension of the disease and treatment should improve adherence, as has been shown in other chronic diseases such as diabetes.
To assess the risk of transformation associated with non-adherence, we analyzed the events (thrombosis, phe- notypic evolution) that occurred before compilation of the questionnaire (retrospective study) and followed up the cohort prospectively. The frequencies of events before compilation of the questionnaire (median time of observa- tion of 11.7 years) were similar in treatment adherent and non-adherent patients. Thrombotic events occurred in 19.2% of treatment adherent and 25.5% of treatment non-adherent patients. These frequencies are slightly higher than those reported for patients with PV (26.4% versus 9.3-19%) and in accordance with the scientific liter- ature for patients with ET (18.2% versus 7.6-22%).17
Regarding the events that occurred during the prospec- tive follow-up, the median time was shorter (1.8 years). However, events were recorded in 35 (12.2%) patients. No differences were noted between the treatment adher- ent and non-adherent groups regarding thrombotic events or death, but phenotypic evolution was more frequent in the treatment non-adherent patients, especially in group 1. Although this result must be interpreted with caution given the small number of affected patients (n=7), the impact of adherence on phenotypic evolution of MPN is reminiscent of data reported for chronic myeloid leukemia or acute lymphoblastic leukemia, confirming the importance of constant therapeutic pressure for the control of malignant clones. Unexpectedly, the impact on thrombosis was less obvious. This may be related to the fact that thrombosis is a more acute event, depending on the immediate hemostatic status at the time of thrombus constitution, whereas the phenotypic evolution of chron- ic hematologic malignancies may be more the result of long-term evolution of the clone, reflecting its exposure to therapeutic pressure. This is coherent with the obser- vation that treatment non-adherent patients were less likely to achieve a complete hematologic response. Only a few events were observed in group 2, suggesting that interferon may ensure better long-term control of MPN clones as has been suggested in recent publications.18 Further evaluation of the long-term impact of non-adher-
Figure 2. Kaplan-Meier evolution-free survival curves for treatment adherent or non-adherent patients.
haematologica | 2018; 103(4)