钙网蛋白突变对芦可替尼治疗期间骨髓纤维化的治疗及生存结局的影响
Impact of calreticulin mutations on treatment and survival outcomes in myelofibrosis during ruxolitinib therapy.
作者信息
Palandri Francesca, Branzanti Filippo, Morsia Erika, Dedola Alessandra, Benevolo Giulia, Tiribelli Mario, Beggiato Eloise, Farina Mirko, Martino Bruno, Caocci Giovanni, Pugliese Novella, Tieghi Alessia, Crugnola Monica, Binotto Gianni, Cavazzini Francesco, Abruzzese Elisabetta, Isidori Alessandro, Scalzulli Emilia, D'Agostino Domenico, Caserta Santino, Nardo Antonella, Lemoli Roberto Massimo, Cilloni Daniela, Bocchia Monica, Pane Fabrizio, Heidel Florian H, Palumbo Giuseppe A, Breccia Massimo, Elli Elena M, Bonifacio Massimiliano
机构信息
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Bologna, Italy.
Institute of Hematology "L. and A. Seràgnoli", IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Massarenti 9, Bologna (BO), 40138, Italy.
出版信息
Ann Hematol. 2025 Jan;104(1):241-251. doi: 10.1007/s00277-025-06204-5. Epub 2025 Jan 20.
Calreticulin (CALR) mutations are detected in around 20% of patients with primary and post-essential thrombocythemia myelofibrosis (MF). Regardless of driver mutations, patients with splenomegaly and symptoms are generally treated with JAK2-inhibitors, most commonly ruxolitinib. Recently, new therapies specifically targeting the CALR mutant clone have entered clinical investigation. To collect information on efficacy and safety of ruxolitinib in CALR-mutated patients, we report a sub-analysis of the "RUX-MF" (NCT06516406) study, comprising 135 CALR-mutated and 786 JAK2-mutated ruxolitinib-treated patients. Compared to JAK2-mutated patients, CALR-mutated patients started ruxolitinib with a more severe disease (higher peripheral blast counts, lower hemoglobin levels and worse marrow fibrosis) and after a longer median time from diagnosis (2.6 versus 0.7 years, p < 0.001). At 6 months, spleen responses were numerically inferior in CALR-mutated patients, who also had significantly lower rates of symptom responses (56.1% versus 66.7%, p = 0.04).
约20%的原发性和原发性血小板增多症后骨髓纤维化（MF）患者检测到钙网蛋白（CALR）突变。无论驱动突变如何，有脾肿大和症状的患者通常使用JAK2抑制剂治疗，最常用的是芦可替尼。最近，专门针对CALR突变克隆的新疗法已进入临床研究。为收集芦可替尼在CALR突变患者中的疗效和安全性信息，我们报告了“RUX-MF”（NCT06516406）研究的亚组分析，该研究包括135例接受芦可替尼治疗的CALR突变患者和786例JAK2突变患者。与JAK2突变患者相比，CALR突变患者开始使用芦可替尼时病情更严重（外周原始细胞计数更高、血红蛋白水平更低且骨髓纤维化更严重），且从诊断到开始治疗的中位时间更长（2.6年对0.7年，p<0.001）。在6个月时，CALR突变患者的脾脏反应在数值上较差，其症状缓解率也显著较低（56.1%对66.7%，p=0.04）。
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