The University of Texas MD Anderson Cancer Center, Division of Cancer Medicine, 1515 Holcombe Blvd, Unit 418, Houston, TX, 77030, USA.
Stanford Cancer Institute, Stanford, CA, USA.
J Hematol Oncol. 2017 Sep 29;10(1):156. doi: 10.1186/s13045-017-0527-7.
Myelofibrosis (MF) is associated with a variety of burdensome symptoms and reduced survival compared with age-/sex-matched controls. This analysis evaluated the long-term survival benefit with ruxolitinib, a Janus kinase (JAK)1/JAK2 inhibitor, in patients with intermediate-2 (int-2) or high-risk MF.
This was an exploratory analysis of 5-year data pooled from the phase 3 COMFORT-I and -II trials. In both trials, patients could cross over to ruxolitinib from the control group (COMFORT-I, placebo; COMFORT-II, best available therapy). All continuing patients in the control groups crossed over to ruxolitinib by the 3-year follow-up. Overall survival (OS; a secondary endpoint in both trials) was evaluated using pooled intent-to-treat data from patients randomized to ruxolitinib or the control groups. OS was also evaluated in subgroups stratified by baseline anemia and transfusion status at week 24.
A total of 528 patients were included in this analysis; 301 were originally randomized to ruxolitinib (COMFORT-I, n = 155; COMFORT-II, n = 146) and 227 to control (n = 154 and n = 73, respectively). The risk of death was reduced by 30% among patients randomized to ruxolitinib compared with patients in the control group (median OS, 5.3 vs 3.8 years, respectively; hazard ratio [HR], 0.70 [95% CI, 0.54-0.91]; P = 0.0065). After correcting for crossover using a rank-preserving structural failure time (RPSFT) method, the OS advantage was more pronounced for patients who were originally randomized to ruxolitinib compared with patients who crossed over from control to ruxolitinib (median OS, 5.3 vs 2.3 years; HR [ruxolitinib vs RPSFT], 0.35 [95% CI, 0.23-0.59]). An analysis of OS censoring patients at the time of crossover also demonstrated that ruxolitinib prolonged OS compared with control (median OS, 5.3 vs 2.4 years; HR [ruxolitinib vs censored at crossover], 0.53 [95% CI, 0.36-0.78]; P = 0.0013). The survival benefit with ruxolitinib was observed irrespective of baseline anemia status or transfusion requirements at week 24.
These findings support ruxolitinib treatment for patients with int-2 or high-risk MF, regardless of anemia or transfusion status. Further analyses will be important for exploring ruxolitinib earlier in the disease course to assess the effect on the natural history of MF.
ClinicalTrials.gov identifiers, NCT00952289 and NCT00934544 .
与年龄和性别匹配的对照组相比，骨髓纤维化（MF）患者存在各种负担性症状和降低的生存。本分析评估了 JAK1/JAK2 抑制剂芦可替尼对中危-2（int-2）或高危 MF 患者的长期生存获益。
这是对来自 3 期 COMFORT-I 和 -II 试验的 5 年数据的探索性分析。在两项试验中，患者可以从对照组交叉到芦可替尼（COMFORT-I，安慰剂；COMFORT-II，最佳可用疗法）。所有继续接受对照组治疗的患者在 3 年随访时交叉到芦可替尼。使用随机分配至芦可替尼或对照组的患者的意向治疗数据评估总生存（OS；两项试验的次要终点）。还根据基线时的贫血和第 24 周的输血状态对亚组进行了 OS 评估。
本分析共纳入 528 例患者；301 例最初随机分配至芦可替尼（COMFORT-I，n=155；COMFORT-II，n=146），227 例分配至对照组（n=154 和 n=73）。与对照组相比，随机分配至芦可替尼的患者死亡风险降低了 30%（中位 OS，分别为 5.3 年和 3.8 年；风险比[HR]，0.70[95%CI，0.54-0.91]；P=0.0065）。使用秩保持结构失效时间（RPSFT）方法校正交叉后，与从对照组交叉至芦可替尼的患者相比，最初随机分配至芦可替尼的患者的 OS 优势更为明显（中位 OS，5.3 年和 2.3 年；HR[芦可替尼 vs RPSFT]，0.35[95%CI，0.23-0.59]）。对交叉时将患者 OS 删失的分析也表明，与对照组相比，芦可替尼延长了 OS（中位 OS，5.3 年和 2.4 年；HR[芦可替尼 vs 交叉时删失]，0.53[95%CI，0.36-0.78]；P=0.0013）。芦可替尼的生存获益与基线时的贫血状态或第 24 周的输血需求无关。
这些发现支持为 int-2 或高危 MF 患者使用芦可替尼治疗，无论贫血或输血状态如何。进一步的分析对于探索在疾病早期使用芦可替尼以评估其对 MF 自然史的影响非常重要。
ClinicalTrials.gov 标识符，NCT00952289 和 NCT00934544。
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