Kiladjian Jean-Jacques, Vannucchi Alessandro M, Gerds Aaron T, Gupta Vikas, Verstovsek Srdan, Egyed Miklos, Platzbecker Uwe, Mayer Jiří, Grosicki Sebastian, Illés Árpád, Woźny Tomasz, Oh Stephen T, McLornan Donal, Kirgner Ilya, Yoon Sung-Soo, Harrison Claire N, Klencke Barbara, Huang Mei, Kawashima Jun, Mesa Ruben
Université de Paris, AP-HP, Hôpital Saint-Louis, Centre d'Investigations Cliniques, INSERM, Paris, France.
Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms (CRIMM), University of Florence, Careggi University Hospital, Florence, Italy.
Hemasphere. 2023 Oct 27;7(11):e963. doi: 10.1097/HS9.0000000000000963. eCollection 2023 Nov.
The oral activin A receptor type I, Janus kinase 1 (JAK1), and JAK2 inhibitor momelotinib demonstrated symptom, spleen, and anemia benefits in intermediate- and high-risk myelofibrosis (MF). Post hoc analyses herein evaluated the efficacy and safety of momelotinib in patients with MF and thrombocytopenia (platelet counts <100 × 10/L) from randomized phase 3 studies: MOMENTUM (momelotinib versus danazol; JAK inhibitor experienced); SIMPLIFY-1 (momelotinib versus ruxolitinib; JAK inhibitor naïve); and SIMPLIFY-2 (momelotinib versus best available therapy; JAK inhibitor experienced); these studies were not statistically powered to assess differences in thrombocytopenic subgroups, and these analyses are descriptive. The treatment effect of momelotinib versus ruxolitinib on week 24 response rates (spleen volume reduction ≥35%/Total Symptom Score reduction ≥50%/transfusion independence) was numerically comparable or better in thrombocytopenic patients versus the overall JAK inhibitor naive population; rates were preserved with momelotinib in thrombocytopenic patients but attenuated with ruxolitinib (momelotinib: 27%/28%/67% overall versus 39%/35%/61% in thrombocytopenic group; ruxolitinib: 29%/42%/49% overall versus 0%/22%/39% in thrombocytopenic group, respectively). In contrast to ruxolitinib, momelotinib maintained high dose intensity throughout the treatment. In the JAK inhibitor experienced population, thrombocytopenic patients had the following: (1) numerically higher symptom and transfusion independence response rates with momelotinib than in control arms; and (2) preserved spleen, symptom, and transfusion independence response rates with momelotinib relative to the overall study populations. The safety profile of momelotinib in thrombocytopenic patients was also consistent with the overall study population. In summary, momelotinib represents a safe and effective treatment option for patients with MF and moderate-to-severe thrombocytopenia.
口服激活素A受体I型、Janus激酶1（JAK1）和JAK2抑制剂莫美替尼在中高危骨髓纤维化（MF）患者中显示出对症状、脾脏和贫血有益。本文的事后分析评估了莫美替尼在随机3期研究中MF合并血小板减少症（血小板计数<100×10⁹/L）患者中的疗效和安全性：MOMENTUM（莫美替尼对比达那唑；有JAK抑制剂使用经验）；SIMPLIFY-1（莫美替尼对比鲁索替尼；无JAK抑制剂使用经验）；以及SIMPLIFY-2（莫美替尼对比最佳可用疗法；有JAK抑制剂使用经验）；这些研究在统计学上没有足够的效力来评估血小板减少亚组之间的差异，这些分析是描述性的。与总体无JAK抑制剂使用经验的人群相比，莫美替尼对比鲁索替尼在第24周时对血小板减少症患者的缓解率（脾脏体积缩小≥35%/总症状评分降低≥50%/输血独立性）在数值上相当或更好；血小板减少症患者使用莫美替尼时缓解率得以维持，但使用鲁索替尼时缓解率降低（莫美替尼：总体为27%/28%/67%，血小板减少症组为39%/35%/61%；鲁索替尼：总体为29%/42%/49%，血小板减少症组分别为0%/22%/39%）。与鲁索替尼不同，莫美替尼在整个治疗过程中维持了高剂量强度。在有JAK抑制剂使用经验的人群中，血小板减少症患者有以下情况：（1）使用莫美替尼时症状和输血独立性缓解率在数值上高于对照组；（2）与总体研究人群相比，使用莫美替尼时脾脏、症状和输血独立性缓解率得以维持。莫美替尼在血小板减少症患者中的安全性概况也与总体研究人群一致。总之，莫美替尼是MF合并中重度血小板减少症患者的一种安全有效的治疗选择。
