PB2222 EFFICACY AND SAFETY OF ANAGRELIDE AS A FIRST‐LINE DRUG IN CYTOREDUCTIVE TREATMENT‐NAÏVE ET PATIENTS IN A REAL WORLD SETTING
Authors: Y. Hashimoto, T. Ito, Y. Tanaka, A. Nakaya, S. Fujita, A. Satake, T. Nakanishi, A. Konishi, M. Hotta, H. Yoshimura, K. Ishii, A. Hashimoto, T. Kondo, H. Omura, I. Shinzato, T. Tanaka, S. Nomura
Journal: HemaSphere (2019)

Background: The goal of treating essential thrombocythemia (ET) is to prevent the potential onset of thrombohemorrhagic events (THEs) and disease progression to myelofibrosis (MF) and acute leukemia (AL). For ET patients who are at a high risk of developing thrombosis, the administration of antiplatelet and cytoreductive treatments is recommended. Anagrelide, a drug used in cytoreductive therapy, was approved in the United States in 1997 for treating thrombocytosis associated with myeloproliferative neoplasms. Although anagrelide is positioned as a second‐line drug in Europe, it has been approved as a first‐line drug in Japan and several other countries. Currently, the United States and Europe have different views regarding the use of anagrelide, and debates about its efficacy and safety are ongoing. Aims: This study aimed to retrospectively assess the efficacy and safety of anagrelide in cytoreductive treatment‐naïve ET patients in a real world setting. Methods: Data of 53 ET patients administered anagrelide as a first‐line treatment were reviewed with respect to patient characteristics, status of antiplatelet and cytoreductive treatments, therapeutic effects, adverse events, development of THEs after treatment, progression to MF or AL after treatment, and cause of death. Results: The median duration of anagrelide administration was 642 days, and the median daily dosage was 1.44 mg/day. The rate of achieving a platelet count &lt;600 × 10 9 /L was 83.0%, and the median duration of time required for the achievement was 53 days. Treatment‐related adverse events occurred in 32 of 53 patients (60.4%). The reported adverse events tended to be slightly more severe in patients with heart failure but were mostly tolerable. The median observation period was 4.1 years, and 12 patients (22.6%) developed THEs during the follow‐up, i.e., thrombotic events in 8 patients (15.1%) and bleeding events in 4 (7.5%). Transformation occurred in 3 patients, all of which were MF. Comparisons between patients who were positive for the JAK2V617F mutation ( JAK2 ‐ET group: 34 patients) and those positive for the CALR mutation ( CALR ‐ET group: 11 patients) revealed that anagrelide demonstrated equivalent therapeutic effects between the two groups and showed no significant differences in white blood cell counts, hemoglobin counts, and rates of decrease in platelet counts. The incidence of anemia as an adverse event was significantly higher in the CALR ‐ET group than in the JAK2 ‐ET group. Favorable platelet counts were also achieved in cases wherein hydroxyurea was introduced as a replacement of anagrelide (8 patients) or in addition to anagrelide (9 patients) owing to unresponsiveness or intolerance to treatment. Summary/Conclusion: In Japanese ET patients who are cytoreductive treatment naïve, the administration of anagrelide as a first‐line drug demonstrated favorable effects in reducing platelet counts, along with safety profiles generally consistent with those reported previously. Although the therapeutic effects of anagrelide are the same regardless of the genetic mutation profiles, ET patients who are positive for the CALR mutation should be closely monitored for the development of anemia as an adverse event. To alleviate the adverse events of anagrelide, the drug can be administered in combination with hydroxyurea, for instance, and the treatment plan should be formulated in such a way that it can maximize the benefits of the two drugs.