Real-world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: data from 95 consecutive patients treated in a compassionate use program. A study from the Swedish Chronic Lymphocytic Leukemia Group
Real-world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: data from 95 consecutive patients treated in a compassionate use program. A study from the Swedish Chronic Lymphocytic Leukemia Group
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DOI：
10.3324/haematol.2016.144576
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发表时间：
2016-12-01
期刊：
影响因子：
10.1
通讯作者：
Osterborg, Anders
中科院分区：
文献类型：
--
作者：
Winqvist, Maria;Asklid, Anna;Osterborg, Anders
伊布替尼是一种布鲁顿酪氨酸激酶抑制剂，已被批准用于复发/难治性和del（17 p）/TP 53突变的慢性淋巴细胞白血病。在肿瘤学领域，临床试验和常规医疗保健之间的差异是常见的。在此，我们报告了95例预后不良的瑞典患者在同情使用项目中接受伊克替尼治疗的真实结果。2014年5月至2015年5月期间，95例连续患者（93例慢性淋巴细胞白血病，2例小淋巴细胞白血病）被纳入研究。中位年龄为69岁。63%有del（17 p）/TP 53突变，65%有Rai III/IV期，28%有淋巴结肿大>= 10 cm。患者接受伊鲁替尼420 mg每日一次治疗，直至疾病进展。在中位随访10.2个月时，总体缓解率为84%（亚组间一致），77%保持无进展。del（17 p）/TP 53突变患者的无进展生存期和总生存期显著缩短（P=0.017和P=0.027，log-rank检验）;考克斯比例回归风险模型中无其他因素显著。伊布替尼耐受性良好。46%的患者发生血肿，无任何大出血。7名患者出现里希特转化。对来自明确定义的地理区域的连续慢性淋巴细胞白血病患者的真实世界分析显示，伊鲁替尼的疗效和安全性与关键试验相似。然而，del（17 p）/TP 53突变仍然是治疗挑战。由于不超过一半的患者有资格参加关键性的伊布替尼试验（RESONATE），我们的研究强调，未来应仔细考虑慢性淋巴细胞白血病的新药物和新适应症的真实结果。
Ibrutinib, a Bruton's tyrosine kinase inhibitor is approved for relapsed/refractory and del(17p)/TP53 mutated chronic lymphocytic leukemia. Discrepancies between clinical trials and routine healthcare are commonly observed in oncology. Herein we report real-world results for 95 poor prognosis Swedish patients treated with ibrutinib in a compassionate use program. Ninety-five consecutive patients (93 chronic lymphocytic leukemia, 2 small lymphocytic leukemia) were included in the study between May 2014 and May 2015. The median age was 69 years. 63% had del(17p)/TP53 mutation, 65% had Rai stage III/IV, 28% had lymphadenopathy >= 10cm. Patients received ibrutinib 420 mg once daily until progression. At a median follow-up of 10.2 months, the overall response rate was 84% (consistent among subgroups) and 77% remained progression-free. Progression-free survival and overall survival were significantly shorter in patients with del(17p)/TP53 mutation (P=0.017 and P=0.027, log-rank test); no other factor was significant in Cox proportional regression hazards model. Ibrutinib was well tolerated. Hematomas occurred in 46% of patients without any major bleeding. Seven patients had Richter's transformation. This real-world analysis on consecutive chronic lymphocytic leukemia patients from a well-defined geographical region shows the efficacy and safety of ibrutinib to be similar to that of pivotal trials. Yet, del(17p)/TP53 mutation remains a therapeutic challenge. Since not more than half of our patients would have qualified for the pivotal ibrutinib trial (RESONATE), our study emphasizes that real-world results should be carefully considered in future with regards to new agents and new indications in chronic lymphocytic leukemia.