高危原发性血小板增多症和真性红细胞增多症患者接受羟基脲或聚乙二醇干扰素α-2a 治疗后的症状负担和生活质量：MPN-RC 111 和 112 试验的事后分析。
Symptom burden and quality of life in patients with high-risk essential thrombocythaemia and polycythaemia vera receiving hydroxyurea or pegylated interferon alfa-2a: a post-hoc analysis of the MPN-RC 111 and 112 trials.
机构信息
Department of Quantitative Health Sciences, Mayo Clinic, Scottsdale, AZ, USA.
Department of Quantitative Health Sciences, Mayo Clinic, Scottsdale, AZ, USA.
出版信息
Lancet Haematol. 2022 Jan;9(1):e38-e48. doi: 10.1016/S2352-3026(21)00343-4.
BACKGROUND
Patients with essential thrombocythaemia or polycythaemia vera have several symptoms that can worsen their quality of life. We aimed to assess how symptom burden changes over time with cytoreductive therapy.
METHODS
We performed a post-hoc analysis of data from MPN-RC 111-a single-arm, open-label, phase 2, multicentre trial at 17 hospitals and cancer centres in Italy and the USA, evaluating the clinical-haematological response to pegylated interferon alfa-2a in patients who were resistant or intolerant to hydroxyurea (NCT01259817)-and MPN-RC 112-a randomised, open-label, phase 3, multicentre trial at 25 hospitals and cancer centres in France, Germany, Israel, Italy, the UK, and the USA, comparing the clinical-haematological response to pegylated interferon alfa-2a versus hydroxyurea in therapy-naive patients with either high-risk essential thrombocythaemia or polycythaemia vera (NCT01258856). Patients completed the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and the European Organisation for the Research and Treatment of Cancer Core Quality of Life Questionnaire through 12 months after initiation of treatment as secondary endpoints. In this post-hoc analysis, we examined the association of symptom burden with the clinical-haematological response at 12 months and the effect of baseline symptom burden (ie, high burden [total symptom score ≥20] vs low burden [total symptom score <20]) on subsequent changes in symptoms, estimated via mixed models. A clinically significant improvement in symptom burden was defined as 50% or greater improvement in the MPN-SAF total symptom score from baseline to 12 months in patients with a total symptom score greater than zero at baseline.
FINDINGS
135 patients were enrolled in MPN-RC 111 between Feb 15, 2012, and Dec 23, 2015, and 168 were enrolled in MPN-RC 112 between Sept 24, 2011, and June 30, 2016. For this analysis, we included data from 114 patients from MPN-RC 111 (64 [56%] with essential thrombocythaemia and 50 [44%] with polycythaemia vera; 56 [49%] were female, and 100 [91%] of 110 were white) and 166 patients from MPN-RC 112 (79 [48%] with essential thrombocythaemia and 87 [52%] with polycythaemia vera; 68 [41%] were female, and 145 [93%] of 156 were white). At 12 months, a clinically significant improvement in symptom burden was reported by 12 (32%) of 38 complete responders and seven (20%) of 35 partial responders treated with pegylated interferon alfa-2a in MPN-RC 111; five (19%) of 27 complete responders and six (18%) of 34 partial responders treated with pegylated interferon alfa-2a in MPN-112; and eight (27%) of 30 complete responders and six (22%) of 27 partial responders treated with hydroxyurea in MPN-112. More complete and partial responders reported a clinically significant improvement than did non-responders (44 [22%] of 191 complete and partial responders vs four [5%] of 76 non-responders; Fisher's exact p=0·0003). Symptom burden improved between 3 and 12 months in patients with high baseline symptom burden, both those treated with pegylated interferon alfa-2a (mean total symptom score change -10·2, 95% CI -13·2 to -7·2) and those treated with hydroxyurea (-6·8, -11·2 to -2·4). However, symptom burden worsened between 3 and 12 months in patients with low baseline symptom burden (patients treated with pegylated interferon alfa-2a: mean total symptom score change 3·2, 95% CI 0·9 to 5·4; patients treated with hydroxyurea: 3·4, 0·6 to 6·2).
INTERPRETATION
Results can inform treatment decisions, including treatment timing and goals in managing essential thrombocythaemia and polycythaemia vera, because measuring symptom burden from the patient perspective is crucial to understanding treatment efficacy and tolerability.
FUNDING
US National Cancer Institute of the National Institutes of Health, and Roche Genentech.
背景
原发性血小板增多症或真性红细胞增多症患者存在多种可降低生活质量的症状。本研究旨在评估细胞减少治疗过程中症状负担的变化情况。
方法
我们对意大利和美国 17 家医院和癌症中心开展的 MPN-RC 111（一项评估聚乙二醇干扰素α-2a 治疗对羟基脲耐药或不耐受患者的临床血液学应答的单臂、开放标签、2 期、多中心试验[NCT01259817]）和法国、德国、以色列、意大利、英国和美国 25 家医院和癌症中心开展的 MPN-RC 112（一项评估聚乙二醇干扰素α-2a 治疗初治高危原发性血小板增多症或真性红细胞增多症患者的临床血液学应答的随机、开放标签、3 期、多中心试验[NCT01258856]）的数据进行了一项事后分析。这两项试验均将患者完成的多发性骨髓瘤症状评估量表（MPN-SAF）和欧洲癌症研究与治疗组织核心生活质量问卷作为次要终点，评估治疗开始后 12 个月时的症状。在本事后分析中，我们通过混合模型，评估了症状负担与 12 个月时临床血液学应答之间的相关性，以及基线症状负担（即高负担[总症状评分≥20]与低负担[总症状评分<20]）对随后症状变化的影响。将 MPN-SAF 总症状评分从基线改善≥50%且基线时总症状评分大于零的患者定义为症状负担有临床意义的改善。
结果
2012 年 2 月 15 日至 2015 年 12 月 23 日，135 例患者入组 MPN-RC 111，2011 年 9 月 24 日至 2016 年 6 月 30 日，168 例患者入组 MPN-RC 112。在本分析中，我们纳入了 MPN-RC 111 中 114 例患者的数据（64 例[56%]为原发性血小板增多症，50 例[44%]为真性红细胞增多症；56 例[49%]为女性，110 例中有 100 例[91%]为白人）和 MPN-RC 112 中 166 例患者的数据（79 例[48%]为原发性血小板增多症，87 例[52%]为真性红细胞增多症；68 例[41%]为女性，156 例中有 145 例[93%]为白人）。在 MPN-RC 111 中，12 例（32%）接受聚乙二醇干扰素α-2a 治疗的完全应答者和 7 例（20%）部分应答者报告症状负担有临床意义的改善；MPN-RC 112 中，5 例（19%）接受聚乙二醇干扰素α-2a 治疗的完全应答者和 6 例（18%）部分应答者报告症状负担有临床意义的改善；MPN-RC 112 中，8 例（27%）接受羟基脲治疗的完全应答者和 6 例（22%）部分应答者报告症状负担有临床意义的改善。与非应答者相比，更多的完全和部分应答者报告症状负担有临床意义的改善（191 例完全和部分应答者中有 44 例[22%]，76 例非应答者中有 4 例[5%]；Fisher 确切概率法，p=0·0003）。高基线症状负担患者的症状负担在 3 至 12 个月间有所改善，包括接受聚乙二醇干扰素α-2a 治疗的患者（总症状评分平均变化-10·2，95%CI -13·2 至-7·2）和接受羟基脲治疗的患者（-6·8，-11·2 至-2·4）。然而，低基线症状负担患者的症状负担在 3 至 12 个月间恶化（接受聚乙二醇干扰素α-2a 治疗的患者：总症状评分平均变化 3·2，95%CI 0·9 至 5·4；接受羟基脲治疗的患者：3·4，0·6 至 6·2）。
结论
结果可为治疗决策提供信息，包括原发性血小板增多症和真性红细胞增多症的治疗时机和目标，因为从患者角度衡量症状负担对了解治疗效果和耐受性至关重要。
资金来源
美国国立卫生研究院美国国家癌症研究所和罗氏/基因泰克。
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