Department of Hematology, Zealand University Hospital, Roskilde, Denmark.
Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Blood Adv. 2024 Oct 22;8(20):5416-5425. doi: 10.1182/bloodadvances.2024013170.
We report the 2-year end-of-study results from the phase 2 COMBI II clinical trial investigating the combination treatment of ruxolitinib and low-dose pegylated interferon alfa-2a in patients with newly diagnosed polycythemia vera (PV). The primary outcome was safety and key secondary endpoints were efficacy, based on hematologic parameters, quality-of-life measurements, and JAK2V617F variant allele frequency (VAF). We used the 2013 European LeukemiaNet and International Working Group-Myeloproliferative Neoplasms Research remission criteria. The remission criteria included remissions in symptoms, splenomegaly, peripheral blood counts, and bone marrow. We included 25 patients with PV with a median age of 70 years; 5 of those had prior thromboembolic events and 3 had computed tomography-verified splenomegaly. Two patients stopped both study drugs; 1 of these due to progression to post-PV myelofibrosis, the only one with a grade 3 infection. No events of herpes zoster infections were observed. None of the patients discontinued treatment due to psychiatric symptoms. The peripheral blood cell count remission rate was 92% at 24 months. Using the 2013 European LeukemiaNet and International Working Group-Myeloproliferative Neoplasms Research remission criteria, 14 (56%) achieved remission at 24 months; 3 (12%) achieved complete remission and 11 (44%) achieved partial remission. The following items from the Myeloproliferative Neoplasm Symptom Total Symptom Score were significantly reduced: abdominal discomfort, night sweats, itching, and bone pain. The median JAK2V617F VAF decreased from 47% (95% confidence interval [CI], 35-59) to 7% (95% CI, 3-15), and 60% of patients achieved molecular remission. In conclusion, combination treatment improved cell counts; bone marrow cellularity, and fibrosis; and decreased JAK2V617F VAF; with acceptable toxicity in patients with PV. The trial was registered at www.clinicaltrialsregister.eu as #EudraCT2018-004150-13.
我们报告了 COMBI II 期临床试验的 2 年研究结果，该试验旨在研究芦可替尼联合低剂量聚乙二醇干扰素 alfa-2a 治疗新诊断的原发性骨髓纤维化（PV）患者的疗效。主要终点为安全性，关键次要终点为基于血液学参数、生活质量测量和 JAK2V617F 变异等位基因频率（VAF）的疗效。我们使用了 2013 年欧洲白血病网络和国际工作组-骨髓增生性肿瘤研究缓解标准。缓解标准包括症状、脾肿大、外周血计数和骨髓缓解。我们纳入了 25 名中位年龄为 70 岁的 PV 患者，其中 5 名患者有血栓栓塞事件史，3 名患者有计算机断层扫描验证的脾肿大。2 名患者停止了两种研究药物的治疗；其中 1 名因进展为 PV 后骨髓纤维化而停药，这也是唯一 1 例 3 级感染的患者。未观察到带状疱疹感染事件。没有患者因精神症状而停止治疗。24 个月时外周血细胞计数缓解率为 92%。使用 2013 年欧洲白血病网络和国际工作组-骨髓增生性肿瘤研究缓解标准，24 个月时 14 名（56%）患者达到缓解；3 名（12%）患者达到完全缓解，11 名（44%）患者达到部分缓解。多发性骨髓瘤症状总评分中的以下项目显著降低：腹部不适、夜间盗汗、瘙痒和骨痛。JAK2V617F VAF 中位数从 47%（95%置信区间[CI]，35-59）降至 7%（95%CI，3-15），60%的患者达到分子缓解。总之，联合治疗改善了 PV 患者的细胞计数、骨髓细胞和纤维化程度，降低了 JAK2V617F VAF，且毒性可接受。该试验在 www.clinicaltrialsregister.eu 上注册，编号为 EudraCT2018-004150-13。
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