P1046: treatment comparison of hydroxyurea vs ruxolitinib in essential thrombocythemia (et): a matched cohort analysis

Topic: 16. Myeloproliferative neoplasms - Clinical Background: ET is characterized by uncontrolled platelet (PLT) production and clonal hematopoiesis leading to increased risk of vascular complications and high symptom burden. In patients (pts) with high-risk ET, hydroxyurea is the preferred first-line cytoreductive treatment; however, many pts are intolerant or refractory to hydroxyurea. Ruxolitinib (RUX) has been shown to improve symptoms in pts with ET; however, whether switching from hydroxyurea to RUX provides improved clinical benefit is unknown. Aims: To compare the clinical outcomes of pts with ET who received hydroxyurea and switched to RUX with those who received hydroxyurea only. Methods: This post hoc analysis compared ET pts refractory or intolerant to hydroxyurea treated with RUX in a phase 2 study (NCT00726232; Pieri. Blood. 2015;125:3352-3; HU-RUX cohort) to pts who received hydroxyurea only in the Myelofibrosis and Essential Thrombocythemia Observational Study (MOST; NCT02953704; HU cohort). Pts were matched 1:1 using propensity score based on age group (<60 y, ≥60 y), sex, body mass index (BMI), duration of ET disease, thrombotic event (TE) history, and EORTC QLQ-C30 global health status score at index (initiation of RUX in HU-RUX and MOST study enrollment in HU). Changes in white blood cell (WBC) counts, PLT counts, and presence of a palpable spleen at 6-mo intervals during the 48-mo follow-up are reported. Results: Of 327 and 39 pts enrolled in MOST and the phase 2 study, who were eligible for this analysis, 37 pts from each study were propensity score-matched and included in HU and HU-RUX cohorts, respectively (at index: age ≥60 y, 27.0% vs 27.0%; women, 64.9% vs 73.0%; median BMI, 24.3 [range, 17.3–31.9] vs 24.5 [17.9–33.7] kg/m2; median disease duration, 5.7 [range, 0–20.9] vs 5.3 [0.4–33.5] y; TE history, 13.5% vs 10.8%; mean [SD] EORTC QLQ-C30 global health status score, 73.0 [22.9] vs 78.6 [20.1]). At index, mean (SD) WBC counts (9.3 [5.1] vs 6.8 [3.1] ×109 L), PLT counts (1027.4 [497.8] vs 513.9 [154.7] ×109 L), and % of pts with palpable spleen (10.0% vs 0%) were higher for HU-RUX vs HU. In HU-RUX, WBC counts decreased from index to 6 mo (mean [SD] change: −1.8 [4.6]), and continued to decrease, reaching a mean (SD) change from index of −3.8 (5.3) at 48 mo (Figure). In HU, mean (SD) change in WBC counts from index remained near zero at 6 and 48 mo (0 [1.8] and −0.1 [2.7]). For HU-RUX vs HU, the difference in mean WBC count change from index was significant at mo 42 (P=0.0138) and significance was maintained through mo 48 (P=0.0182). In HU-RUX, PLT counts decreased rapidly between index and 6 mo (mean [SD] change: −391.7 [472.9]) and declined further thereafter, reaching a mean [SD] change from index of −539.0 (521.8) at 48 mo (Figure). In HU, PLT counts remained unchanged at 6 and 48 mo compared with index (−5.7 [175.3] and −6.9 [105.1]). For HU-RUX vs HU, the difference in mean PLT count change from index was significant at mo 6 (P=0.0002) and significance was maintained through mo 48 (P<0.0001). In HU-RUX, % of pts with palpable spleen decreased from 10.0% at index to 3.7% at 12 mo and to 4.8% at 48 mo. Summary/Conclusion: Pts who switched from hydroxyurea to RUX experienced controlled WBC and PLT counts compared with pts who stayed on hydroxyurea. Pts who switched from hydroxyurea to RUX also showed a reduction in splenomegaly over time. These results demonstrate that switching to RUX after being refractory or intolerant to hydroxyurea may improve clinical outcomes of pts with ET.Keywords: Essential Thrombocytemia, Hydroxyurea, Ruxolitinib, Myeloid malignancies