Ayala Rosa, Fernández Rafael Alonso, García-Gutiérrez Valentín, Alvarez-Larrán Alberto, Osorio Santiago, Sánchez-Pina Jose M, Carreño-Tarragona Gonzalo, Álvarez Noemi, Gómez-Casares María Teresa, Duran Antonia, Gorrochategi Julian, Hernández-Boluda Juan Carlos, Martínez-López Joaquín
Haematological Malignancies Clinical Research Unit Hospital Universitario 12 de Octubre, Universidad Complutense, CNIO, CIBERONC Madrid Spain.
Hematology Department Hospital Universitario 12 de Octubre Madrid Spain.
EJHaem. 2023 Apr 16;4(2):401-409. doi: 10.1002/jha2.685. eCollection 2023 May.
This phase Ib, non-randomized, open-label study evaluates the safety and tolerability of ruxolitinib in combination with nilotinib and prednisone in patients with naïve or ruxolitinib-resistant myelofibrosis (MF). A total of 15 patients with primary or secondary MF received the study treatment; 13 patients had received prior ruxolitinib treatment (86.7%). Eight patients completed seven cycles (53.3%) and six patients completed twelve cycles of treatment (40%). All the patients experienced at least one adverse event (AE) during the study (the most common AEs were hyperglycemia, asthenia, and thrombocytopenia), and 14 patients registered at least one treatment-related AE (the most common treatment-related AEs were hyperglycemia (22.2%; three grade 3 cases). Five treatment-related serious AEs (SAEs) were reported in two patients (13.3%). No deaths were registered throughout the study. No dose-limiting toxicity was observed. Four out of fifteen (27%) patients experienced a 100% spleen size reduction at Cycle 7, and two additional patients achieved a >50% spleen size reduction, representing an overall response rate of 40% at Cycle 7. In conclusion, the tolerability of this combination was acceptable, and hyperglycemia was the most frequent treatment-related AE. Ruxolitinib in combination with nilotinib and prednisone showed relevant clinical activity in patients with MF. This trial was registered with EudraCT Number 2016-005214-21.
这项Ib期、非随机、开放标签研究评估了芦可替尼联合尼洛替尼和泼尼松在初治或对芦可替尼耐药的骨髓纤维化（MF）患者中的安全性和耐受性。共有15例原发性或继发性MF患者接受了研究治疗；13例患者曾接受过芦可替尼治疗（86.7%）。8例患者完成了7个周期的治疗（53.3%），6例患者完成了12个周期的治疗（40%）。所有患者在研究期间均经历了至少一次不良事件（AE）（最常见的AE为高血糖、乏力和血小板减少），14例患者记录了至少一次与治疗相关的AE（最常见的与治疗相关的AE为高血糖（22.2%；3例3级病例）。两名患者报告了5次与治疗相关的严重不良事件（SAE）（13.3%）。整个研究期间未记录到死亡病例。未观察到剂量限制性毒性。15例患者中有4例（27%）在第7周期脾脏大小缩小了100%，另外2例患者脾脏大小缩小>50%，第7周期的总缓解率为40%。总之，这种联合用药的耐受性是可以接受的，高血糖是最常见的与治疗相关的AE。芦可替尼联合尼洛替尼和泼尼松在MF患者中显示出相关的临床活性。该试验已在欧洲临床试验数据库（EudraCT）注册，注册号为2016-005214-21。
