Grunwald Michael R, Ritchie Ellen K, Rumi Elisa, Assad Albert, Hamer-Maansson J E, Yu Jingbo, Kalafut Tricia, Braunstein Evan, Passamonti Francesco
Department of Hematologic Oncology and Blood Disorders Levine Cancer Institute Atrium Health Charlotte North Carolina USA.
Weill Cornell Medical College and New York Presbyterian Hospital New York New York USA.
EJHaem. 2024 Jul 19;5(4):778-783. doi: 10.1002/jha2.954. eCollection 2024 Aug.
Hydroxyurea is the preferred first-line cytoreductive treatment for high-risk essential thrombocythaemia (ET), but many patients are intolerant or refractory to hydroxyurea. Ruxolitinib has been shown to improve symptoms in patients with ET. This post hoc analysis compared the clinical outcomes of patients with ET who received hydroxyurea only with those who switched from hydroxyurea to ruxolitinib due to intolerance/resistance to hydroxyurea. Patients with ET refractory/intolerant to hydroxyurea treated with ruxolitinib in a completed phase 2 study (HU-RUX) were propensity score matched with patients who received hydroxyurea only in an observational study (HU). Changes in leukocyte and platelet counts were reported at 6-month intervals during the 48-month follow-up. Following propensity score matching, 37 patients were included for analysis in each cohort. Mean (standard deviation [SD]) leukocyte and platelet counts at index were higher for HU-RUX versus HU (leukocyte: 9.3 [5.1] vs. 6.8 [3.1] × 10/L; platelet: 1027.4 [497.8] vs. 513.9 [154.7] × 10/L), both of which decreased significantly from index to 6 months through to 48 months in HU-RUX (mean [SD] change from index at 6 months-leukocyte: -1.8 [4.6] × 10/L; platelet: -391.7 [472.9] × 10/L; at 48 months-leukocyte: -3.8 [5.3] × 10/L; platelet: -539.0 [521.8] × 10/L), but remained relatively stable in HU (mean [SD] change from index at 6 months-leukocyte: 0 [1.8] × 10/L; platelet: -5.7 [175.3] × 10/L; at 48 months-leukocyte: -0.1 [2.7] × 10/L; platelet: -6.9 [105.1] × 10/L). In conclusion, these results demonstrate that switching from hydroxyurea to ruxolitinib in patients with ET who are intolerant or refractory to hydroxyurea could improve abnormal haematologic values similar to those who receive first-line hydroxyurea.
羟基脲是高危原发性血小板增多症（ET）首选的一线细胞减灭治疗药物，但许多患者对羟基脲不耐受或难治。鲁索替尼已被证明可改善ET患者的症状。这项事后分析比较了仅接受羟基脲治疗的ET患者与因对羟基脲不耐受/耐药而从羟基脲转换为鲁索替尼治疗的ET患者的临床结局。在一项已完成的2期研究（HU-RUX）中接受鲁索替尼治疗的对羟基脲难治/不耐受的ET患者与在一项观察性研究（HU）中仅接受羟基脲治疗的患者进行倾向评分匹配。在48个月的随访期间，每隔6个月报告白细胞和血小板计数的变化。倾向评分匹配后，每个队列纳入37例患者进行分析。HU-RUX组与HU组相比，基线时白细胞和血小板的平均（标准差[SD]）计数更高（白细胞：9.3[5.1]对6.8[3.1]×10⁹/L；血小板：1027.4[497.8]对513.9[154.7]×10⁹/L），在HU-RUX组中，从基线到6个月直至48个月，白细胞和血小板计数均显著下降（6个月时相对于基线的平均[SD]变化-白细胞：-1.8[4.6]×10⁹/L；血小板：-391.7[472.9]×10⁹/L；48个月时-白细胞：-3.8[5.3]×10⁹/L；血小板：-539.0[521.8]×10⁹/L），但在HU组中相对稳定（6个月时相对于基线的平均[SD]变化-白细胞：0[1.8]×10⁹/L；血小板：-5.7[175.3]×10⁹/L；48个月时-白细胞：-0.1[2.7]×10⁹/L；血小板：-6.9[105.1]×10⁹/L）。总之，这些结果表明，对于对羟基脲不耐受或难治的ET患者，从羟基脲转换为鲁索替尼可改善血液学异常值，类似于接受一线羟基脲治疗的患者。
