PB2233 RUXOLITINIB IN POLYCYTHEMIA VERA PATIENTS: RESPONSE DIFFERENCES BETWEEN IN HYDROXYUREA INTOLERANT AND RESISTANT PATIENTS
Authors: E. González Pérez, F. FernándezFuertes, J. M. Raya Sánchez, K. Mayani, M. Tapia Torres, M. D. L. N. S.á.ez Perdomo, S. Sánchez Sosa, Y. Florido Ortega, C. Bilbao Sieyro, R. Stuckey, M. T. Molero Labarta, M. T. Gómez Casares
Journal: HemaSphere (2019)

Background: Polycythemia vera (PV) is a chronic myeloproliferative neoplasm, characterized by mutation Janus Kinase 2 mutation (JAK2V617), which is present in 95‐97% of the PV patients. Hydroxyurea (HU) therapy has been indicated as the first line cytoreductive treatment in PV patients, but the 25% of patients become resistant or intolerant to HU. Ruxolitinib is a JAK2V617 inhibitor approved for the treatment of patients with HU intolerant/resistant. However, just some real‐life experiences in PV patients resistant or intolerant to HU have been reported to date. Aims: The main aim of this study is the analysis of efficacy of ruxolitinib treatment in HU‐resistant /intolerant PV patients from Canary Island. Methods: We analyzed twenty‐two PV patients that come from four different centers that are not currently included in clinical trials, and they were hydroxyurea resistant or intolerant. Their date of diagnosis ranged from 1993 to 2018. Analytical parameters were extracted from routine analysis. The presence of the JAK2V617F mutation was detected by RT‐PCR. Results: Of the 22 PV resistant or intolerant to hydroxyurea patients, 7 were women (31.82%) and 15 were men (68.18%). Mean age at diagnosis were 59.03 ± 10.23 years. Of the 22 PV patients, 5 (22.73%) were resistant to HU and 17 (77.27%) were intolerant. Maximum HU doses were 2.5 g/24 h (mean range 1.25 ± 0.61 g/24 h), and mean time with HU treatment was 13.33 ± 10.20 months. All patients presented the JAK2V617F mutation. Mean time with ruxolitinib treatment was 50.91 ± 39.98 months. The mean hematological parameters of the PV patients at diagnosis, at time of commencement with ruxolitinib, and date of last hematological analysis is shown in Table 1. Spleen size was a parameter not well indicated in routine practice, so it was deleted from the analysis. According to ELN criteria, 12 (54.55%) patients show, at least, partial response. At the last analysis, no patients had progressed to secondary myelofibrosis and all patients were still alive. ANOVA analysis was performed to infer if there are differences between intolerant and resistant patients. Hematological parameters at diagnosis date, ruxolitinib's commencement and last analysis were analyzed in both groups of patients, as it is shown in table 2. Only in last hematological analysis performed, statically significant differences between resistant and intolerant were presented on hemoglobine, hematocrit and leukocytes mean values, however differences were not appreciate in platelet mean value. This outcomes suggests that HU‐intolerant patients presents better control at hematological level than HU‐resistant patients. Mean of the parameters, standard desviation and significance are indicated in Table 2. In general, adverse effects after commencement with ruxolitinib treatment reported were grade 1 or 2. Just one patient was intolerant to ruxolitinib. Most common non heamatological adverse events were headache and pruritus. Summary/Conclusion: In our serie, 54,55% obtained, at least, partial response with ruxolitinib treatment in patients with HU intolerant/ resistant patients. The outcomes indicate that control at hemoglobin, hematocrite and leukocytes is better in intolerant versus resistant patients. image