Abstract：
BACKGROUND: Follicular helper T-cell lymphomas (TFHL) harbour frequent alterations in genes that regulate DNA methylation. Preliminary reports suggest that treatment with 5-azacitidine has clinical activity in patients with relapsed or refractory TFHL. We aimed to compare the oral form of azacitidine with investigator\'s choice standard therapy (ICT; ie, gemcitabine, bendamustine, or romidepsin) in patients with relapsed or refractory TFHL.
METHODS: Patients older than 18 years with relapsed or refractory TFHL (angioimmunoblastic T-cell lymphoma, follicular lymphoma, or nodal T-cell lymphoma with phenotype, ie, positive with two or more markers among CD10, BCL6, CXCL13, PD1, or ICOS) based on the 2017 WHO classification of haematological neoplasms, with an Eastern Cooperative Oncology Group performance status score of 0-3, were recruited in university hospitals from five European countries and from Japan. Patients were randomly assigned 1:1 to treatment with either azacitidine given at a dose of 300 mg once a day (200 mg in Japanese patients) for 14 days in a 28-day cycle or gemcitabine, bendamustine, or romidepsin according to the investigator\'s choice. Random assignment was stratified by the number of previous lines of therapy and by the presence of previous or concomitant myeloid malignancy. The primary endpoint was investigator-assessed progression-free survival, presented in the intention-to-treat population. This Article is the final analysis of this trial, registered at ClinicalTrials.gov (Europe NCT03593018 and Japan NCT03703375).
RESULTS: 86 patients (median age 69 years [IQR 62-76], 50 patients were male, 36 were female) were enrolled between Nov 9, 2018, to Feb 22, 2021; 42 in the azacitidine group and 44 in the ICT group. With a median follow-up of 27·4 months (IQR 20·2-32·9), the median progression-free survival was 5·6 months (95% CI 2·7 -8·1) in the azacitidine group versus 2·8 months (1·9-4·8) in the ICT group (hazard ratio of 0·63 (95% CI 0·38-1·07); 1-sided p=0·042). Grade 3-4 adverse events were reported in 32 (76%) of 42 patients in the azacitidine group versus 42 (98%) of 43 patients in the ICT group. The most adverse grade 3 or worse adverse events were haematological (28 [67%] of 42 patients vs 40 [93%] of 43 patients), infection (8 [19%] and 14 [33%]), and gastrointestinal (5 [12%] vs 1 [2%] for azacitidine and ICT, respectively). There were two treatment-related deaths in the azacitidine group (one endocarditis and one candidiasis) and three in the ICT group (one heart failure, one COVID-19, and one cause unknown).
CONCLUSIONS: Although the pre-specified primary outcome of the trial was not met, the favourable safety profile suggests that azacitidine could add to the treatment options in these difficult to treat diseases especially in combination with other drugs. Trials with combination are in preparation in a platform trial.
BACKGROUND: Bristol-Myers Squibb.
UNASSIGNED: For the French translation of the abstract see Supplementary Materials section.
METHODS: Patients older than 18 years with relapsed or refractory TFHL (angioimmunoblastic T-cell lymphoma, follicular lymphoma, or nodal T-cell lymphoma with phenotype, ie, positive with two or more markers among CD10, BCL6, CXCL13, PD1, or ICOS) based on the 2017 WHO classification of haematological neoplasms, with an Eastern Cooperative Oncology Group performance status score of 0-3, were recruited in university hospitals from five European countries and from Japan. Patients were randomly assigned 1:1 to treatment with either azacitidine given at a dose of 300 mg once a day (200 mg in Japanese patients) for 14 days in a 28-day cycle or gemcitabine, bendamustine, or romidepsin according to the investigator\'s choice. Random assignment was stratified by the number of previous lines of therapy and by the presence of previous or concomitant myeloid malignancy. The primary endpoint was investigator-assessed progression-free survival, presented in the intention-to-treat population. This Article is the final analysis of this trial, registered at ClinicalTrials.gov (Europe NCT03593018 and Japan NCT03703375).
RESULTS: 86 patients (median age 69 years [IQR 62-76], 50 patients were male, 36 were female) were enrolled between Nov 9, 2018, to Feb 22, 2021; 42 in the azacitidine group and 44 in the ICT group. With a median follow-up of 27·4 months (IQR 20·2-32·9), the median progression-free survival was 5·6 months (95% CI 2·7 -8·1) in the azacitidine group versus 2·8 months (1·9-4·8) in the ICT group (hazard ratio of 0·63 (95% CI 0·38-1·07); 1-sided p=0·042). Grade 3-4 adverse events were reported in 32 (76%) of 42 patients in the azacitidine group versus 42 (98%) of 43 patients in the ICT group. The most adverse grade 3 or worse adverse events were haematological (28 [67%] of 42 patients vs 40 [93%] of 43 patients), infection (8 [19%] and 14 [33%]), and gastrointestinal (5 [12%] vs 1 [2%] for azacitidine and ICT, respectively). There were two treatment-related deaths in the azacitidine group (one endocarditis and one candidiasis) and three in the ICT group (one heart failure, one COVID-19, and one cause unknown).
CONCLUSIONS: Although the pre-specified primary outcome of the trial was not met, the favourable safety profile suggests that azacitidine could add to the treatment options in these difficult to treat diseases especially in combination with other drugs. Trials with combination are in preparation in a platform trial.
BACKGROUND: Bristol-Myers Squibb.
UNASSIGNED: For the French translation of the abstract see Supplementary Materials section.
摘要：
背景：滤泡辅助性T细胞淋巴瘤（TFHL）在调节DNA甲基化的基因中存在频繁的改变。初步报告表明，5-阿扎胞苷治疗对复发或难治性TFHL患者具有临床作用。我们的目的是比较阿扎胞苷的口服形式与研究者选择的标准疗法(ICT；即，吉西他滨,苯达莫司汀,或罗米地辛）在复发或难治性TFHL患者中。
方法：18岁以上复发或难治性TFHL（血管免疫母细胞性T细胞淋巴瘤，滤泡性淋巴瘤,或具有表型的结节性T细胞淋巴瘤，ie,CD10，BCL6，CXCL13，PD1或ICOS中的两种或多种标志物呈阳性），基于2017年WHO血液肿瘤分类，在来自欧洲5个国家和日本的大学医院中招募了东部肿瘤协作组的表现状态得分为0-3分。患者被随机分配为1：1，在28天的周期内，每天一次（日本患者为200mg），持续14天的阿扎胞苷或吉西他滨治疗。苯达莫司汀,或者根据调查员的选择罗米德辛。根据先前治疗路线的数量以及先前或伴随的骨髓性恶性肿瘤的存在对随机分配进行分层。主要终点是研究者评估的无进展生存期，在意向治疗人群中呈现。本文是本次审判的最终分析,在ClinicalTrials.gov注册（欧洲NCT03593018和日本NCT03703375）。
结果：86例患者（中位年龄69岁[IQR62-76]，50名患者为男性，36名女性）在2018年11月9日至2021年2月22日之间注册；阿扎胞苷组42名，ICT组44名。中位随访时间为27·4个月（IQR20·2-32·9），阿扎胞苷组的中位无进展生存期为5·6个月(95%CI2·7-8·1),ICT组为2·8个月(1·9-4·8)(风险比为0·63(95%CI0·38-1·07);单侧p=0·042).阿扎胞苷组42例患者中有32例（76％）发生3-4级不良事件，ICT组43例患者中有42例（98％）发生。最严重的3级或更严重的不良事件是血液学（42例患者中有28例[67%]，43例患者中有40例[93%]）。感染（8[19%]和14[33%]），和胃肠道（阿扎胞苷和ICT为5[12%]vs1[2%]，分别)。阿扎胞苷组2例与治疗相关的死亡（1例心内膜炎和1例念珠菌病），ICT组3例（1例心力衰竭，一种COVID-19，一种原因不明）。
结论：虽然未达到试验的预定主要结果，良好的安全性表明，阿扎胞苷可以增加这些难以治疗疾病的治疗选择，特别是与其他药物联合使用。组合试验正在准备平台试验。
背景：百时美施贵宝。
■有关摘要的法语翻译，请参见补充材料部分。
方法：18岁以上复发或难治性TFHL（血管免疫母细胞性T细胞淋巴瘤，滤泡性淋巴瘤,或具有表型的结节性T细胞淋巴瘤，ie,CD10，BCL6，CXCL13，PD1或ICOS中的两种或多种标志物呈阳性），基于2017年WHO血液肿瘤分类，在来自欧洲5个国家和日本的大学医院中招募了东部肿瘤协作组的表现状态得分为0-3分。患者被随机分配为1：1，在28天的周期内，每天一次（日本患者为200mg），持续14天的阿扎胞苷或吉西他滨治疗。苯达莫司汀,或者根据调查员的选择罗米德辛。根据先前治疗路线的数量以及先前或伴随的骨髓性恶性肿瘤的存在对随机分配进行分层。主要终点是研究者评估的无进展生存期，在意向治疗人群中呈现。本文是本次审判的最终分析,在ClinicalTrials.gov注册（欧洲NCT03593018和日本NCT03703375）。
结果：86例患者（中位年龄69岁[IQR62-76]，50名患者为男性，36名女性）在2018年11月9日至2021年2月22日之间注册；阿扎胞苷组42名，ICT组44名。中位随访时间为27·4个月（IQR20·2-32·9），阿扎胞苷组的中位无进展生存期为5·6个月(95%CI2·7-8·1),ICT组为2·8个月(1·9-4·8)(风险比为0·63(95%CI0·38-1·07);单侧p=0·042).阿扎胞苷组42例患者中有32例（76％）发生3-4级不良事件，ICT组43例患者中有42例（98％）发生。最严重的3级或更严重的不良事件是血液学（42例患者中有28例[67%]，43例患者中有40例[93%]）。感染（8[19%]和14[33%]），和胃肠道（阿扎胞苷和ICT为5[12%]vs1[2%]，分别)。阿扎胞苷组2例与治疗相关的死亡（1例心内膜炎和1例念珠菌病），ICT组3例（1例心力衰竭，一种COVID-19，一种原因不明）。
结论：虽然未达到试验的预定主要结果，良好的安全性表明，阿扎胞苷可以增加这些难以治疗疾病的治疗选择，特别是与其他药物联合使用。组合试验正在准备平台试验。
背景：百时美施贵宝。
■有关摘要的法语翻译，请参见补充材料部分。
