维奈托克(Venetoclax)联合诱导化疗治疗新诊断的急性髓性白血病患者
背景
维奈托克Venclyxto(Venetoclax) 联合强化化疗已被证明是安全的,在新诊断的急性髓系白血病患者中具有良好的活性。本研究的目的是比较维奈托克(Venetoclax)加强化化疗与单独强化化疗的活性。
方法
这是2010年3月29日至2021年6月15日在美国德克萨斯州德克萨斯大学MD安德森癌症中心患者的前瞻性临床试验(NCT03214562,NCT02115295和NCT01289457)的事后倾向评分匹配分析。符合条件的患者年龄在18岁以上,新诊断为急性髓性白血病或高风险骨髓增生异常综合征,并在嘌呤类似物与蒽环类药物和阿糖胞苷联合维奈托克(Venetoclax)加强化化疗或单独强化化疗的试验中进行治疗。维奈托克(Venetoclax)加强化化疗组的患者与强化化疗组的患者相匹配。使用骨髓穿刺和活检以及八色多参数流式细胞术评估形态学反应和可测量的残留病(MRD)。主要目标是MRD阴性复合完全缓解率和异基因造血干细胞移植(HSCT)的累积发生率。所有在两个治疗周期(诱导和再诱导)内有反应的患者均被纳入分析。次要目标包括评估无事件生存期和总生存期。
研究结果
倾向匹配队列包括279名患者(中位年龄49岁[IQR 39-57];131名[47%]为男性,148名[53%]为女性);维奈托克(Venetoclax)加强化化疗队列85人,强化化疗队列194人。中位随访30个月后(95%CI 26-36),维奈托克(Venetoclax)加强化化疗组74名患者中有64名(86%)MRD阴性复合完全缓解率为86[61%]强化化疗组140名患者(奇数比3.2[95%CI 1.5-6.7];p=0.0028)。维奈托克(Venetoclax)联合强化化疗组患者异基因造血干细胞移植总累积发生率高于强化化疗组(79%[95%CI 67-88] vs 57%[49-65];风险比[HR]1.52[95%CI 1.11-2.08];p=0.012)。维奈托克(Venetoclax)加强化化疗可改善无事件生存期(中位数未达到[NR;95%CI NR-NR] vs 14.3个月[10.7-33.5];HR 0.57[95%CI 0(中位数NR[95%CI 24-NR] vs 32个月[19-NR];HR 0.63[95%CI 0.35-1.1],p=0.13)。
解释
维奈托克(Venetoclax)联合强化诱导化疗可诱导深度 MRD 阴性缓解,允许在首次缓解时过渡到同种异体HSCT,并改善无事件生存期。这些结果强调了维奈托克(Venetoclax)在欧洲白血病网络风险组强化诱导化疗中增加的益处,并作为未来验证性前瞻性临床试验入选的基准。
背景
维奈托克Venclyxto(Venetoclax) 联合强化化疗已被证明是安全的,在新诊断的急性髓系白血病患者中具有良好的活性。本研究的目的是比较维奈托克(Venetoclax)加强化化疗与单独强化化疗的活性。
方法
这是2010年3月29日至2021年6月15日在美国德克萨斯州德克萨斯大学MD安德森癌症中心患者的前瞻性临床试验(NCT03214562,NCT02115295和NCT01289457)的事后倾向评分匹配分析。符合条件的患者年龄在18岁以上,新诊断为急性髓性白血病或高风险骨髓增生异常综合征,并在嘌呤类似物与蒽环类药物和阿糖胞苷联合维奈托克(Venetoclax)加强化化疗或单独强化化疗的试验中进行治疗。维奈托克(Venetoclax)加强化化疗组的患者与强化化疗组的患者相匹配。使用骨髓穿刺和活检以及八色多参数流式细胞术评估形态学反应和可测量的残留病(MRD)。主要目标是MRD阴性复合完全缓解率和异基因造血干细胞移植(HSCT)的累积发生率。所有在两个治疗周期(诱导和再诱导)内有反应的患者均被纳入分析。次要目标包括评估无事件生存期和总生存期。
研究结果
倾向匹配队列包括279名患者(中位年龄49岁[IQR 39-57];131名[47%]为男性,148名[53%]为女性);维奈托克(Venetoclax)加强化化疗队列85人,强化化疗队列194人。中位随访30个月后(95%CI 26-36),维奈托克(Venetoclax)加强化化疗组74名患者中有64名(86%)MRD阴性复合完全缓解率为86[61%]强化化疗组140名患者(奇数比3.2[95%CI 1.5-6.7];p=0.0028)。维奈托克(Venetoclax)联合强化化疗组患者异基因造血干细胞移植总累积发生率高于强化化疗组(79%[95%CI 67-88] vs 57%[49-65];风险比[HR]1.52[95%CI 1.11-2.08];p=0.012)。维奈托克(Venetoclax)加强化化疗可改善无事件生存期(中位数未达到[NR;95%CI NR-NR] vs 14.3个月[10.7-33.5];HR 0.57[95%CI 0(中位数NR[95%CI 24-NR] vs 32个月[19-NR];HR 0.63[95%CI 0.35-1.1],p=0.13)。
解释
维奈托克(Venetoclax)联合强化诱导化疗可诱导深度 MRD 阴性缓解,允许在首次缓解时过渡到同种异体HSCT,并改善无事件生存期。这些结果强调了维奈托克(Venetoclax)在欧洲白血病网络风险组强化诱导化疗中增加的益处,并作为未来验证性前瞻性临床试验入选的基准。
【又一款CAR-T疗法获批二线治疗】6月24日,百时美施贵宝(BMS)宣布FDA批准CD19 CAR-T疗法Breyanzi (lisocabtagene maraleucel)新适应症,用于二线治疗成人大B细胞淋巴瘤(LBCL)患者,包括弥漫性大B细胞淋巴瘤(DLBCL)、高级别B细胞淋巴瘤、原发性纵隔大B细胞淋巴瘤、滤泡性淋巴瘤3B级。具体而言,上述相关患者经一线化学免疫治疗无效或在12个月内复发,由于年龄和并发症不适合接受造血干细胞移植(HSCT)。更多详情请戳:https://t.cn/A6a5Yk8a
Engraftment syndrome vs hyper acute GVHD:
ES occurrs at the time of WBC recovery, within 4 days of ANC >500: it is a neutrophils induced pro-inflammatory cytokine release syndrome with capillary leakage, non infectious fever, skin rash, pulmonary edema, hypoxia, renal insufficiency, elevations of t bili, diarrhea and transient encephalopathy. Treatment is early recognition and steroids. It happens in auto or allo-HSCT.
while as risk of super acute GVHD is associated with Engraftment syndrome, and it is hard to differentiate this 2 overlapping disease, acute GVHD occurs within 2-3 weeks of HSCT, with skin GI and liver injuries from GVHD, rather than cytokine release symptoms. The donor is usually non-identical (allo-transplant rather than auto transplant. ). Pls note this pt was auto transplant for treatment of multiple myeloma and first fever was day 4, and cytokine release syndrome on day 10, the time frame is consistent with engraftment of neutrophils. It is therefore a case of ES rather than acute GVHD. This pt need steroids/prednisone as first treatment. Left unrecognized, it can be lethal.
ES occurrs at the time of WBC recovery, within 4 days of ANC >500: it is a neutrophils induced pro-inflammatory cytokine release syndrome with capillary leakage, non infectious fever, skin rash, pulmonary edema, hypoxia, renal insufficiency, elevations of t bili, diarrhea and transient encephalopathy. Treatment is early recognition and steroids. It happens in auto or allo-HSCT.
while as risk of super acute GVHD is associated with Engraftment syndrome, and it is hard to differentiate this 2 overlapping disease, acute GVHD occurs within 2-3 weeks of HSCT, with skin GI and liver injuries from GVHD, rather than cytokine release symptoms. The donor is usually non-identical (allo-transplant rather than auto transplant. ). Pls note this pt was auto transplant for treatment of multiple myeloma and first fever was day 4, and cytokine release syndrome on day 10, the time frame is consistent with engraftment of neutrophils. It is therefore a case of ES rather than acute GVHD. This pt need steroids/prednisone as first treatment. Left unrecognized, it can be lethal.
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