Phase 1/2 Trial of CLAG-M with Dose-Escalated Mitoxantrone in Combination with Fractionated-Dose Gemtuzumab Ozogamicin for Newly Diagnosed Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms.
Phase 1/2 Trial of CLAG-M with Dose-Escalated Mitoxantrone in Combination with Fractionated-Dose Gemtuzumab Ozogamicin for Newly Diagnosed Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms.
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DOI：
10.3390/cancers14122934
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发表时间：
2022-06-14
期刊：
影响因子：
5.2
通讯作者：
Walter RB
中科院分区：
文献类型：
--
作者：
Godwin CD;Rodríguez-Arbolí E;Othus M;Halpern AB;Appelbaum JS;Percival MM;Hendrie PC;Oehler VG;Keel SB;Abkowitz JL;Cooper JP;Cassaday RD;Estey EH;Walter RB
多项研究表明，getuzumab ozogamicin(GO)可改善一些成人急性髓系白血病(AML)强化化疗的疗效，但尚不清楚GO的最佳剂量方案。在这里，我们对66名新诊断的AML或其他高级别髓系肿瘤的成人患者进行了1/2期研究，发现GO(GO)的分次剂量方案可以安全地与克拉里滨、大剂量阿糖胞苷、G-CSF和剂量递增的米托蒽醌(CLAG-M)联合使用。用CLAG-M/GO_3治疗的60例患者中，52例(87%)获得完全缓解(CR)/完全缓解(CR)，血液学不完全恢复(CRI)，45/52(87%)未见血液学残留。6个月和12个月的无事件存活率分别为73%和58%；在有良好风险的患者中，这些估计分别为100%和95%。与单独使用CLAG-M治疗的186名医学匹配的成年人相比，CLAG-M/G03与患有有利风险疾病的患者的存活率更高有关。这些数据表明，在高危AML/高级别髓系肿瘤中，CLAG-M/GO_3比单独使用CLAG-M更安全和有效。Getuzumab ozogamicin(GO)与AML强化化疗一起使用时可改善疗效。一项荟萃分析表明，分次剂量的GO(GO_3)与7+3相结合的益处最大。为了测试GO_3是否可以安全地与高强度化疗一起使用，我们对新诊断的AML或其他高级别髓系肿瘤(NCT03531918)的成年人进行了1/2期研究，其中包括克拉里滨、大剂量阿糖胞苷、G-CSF和剂量递增的米托蒽醌(CLAG-M)(NCT03531918)。66例患者入选，中位年龄65岁(范围：19-80岁)。队列中分别有6名和12名患者在第一阶段接受1剂GO或3剂GO(GO_3)的治疗，每次3 mg/m2。由于没有达到最大耐受剂量，建议的第二阶段剂量(RP2D)被宣布为GO_3。在RP2D时，52/60(87%)患者获得完全缓解(CR)/CR并伴有不完全血液学恢复(CRI)，45/52(87%)患者未见流式细胞术可测残留病(MRD)。8周死亡率为0%。6个月和12个月的无事件生存率(EFS)分别为73%和58%；在有良好风险的患者中，这些估计分别为100%和95%。与单独使用CLAG-M治疗的186名医学上匹配的成年人相比，CLAG-M/GO_3与患有有利风险疾病的患者的存活率更高有关(EFS：P=0.007；OS：P=0.030)。这些数据表明，在有利风险的AML/高级别髓系肿瘤中，CLAG-M/GO_3是安全的，并且比单独使用CLAG-M具有更好的疗效。
Several studies have demonstrated that gemtuzumab ozogamicin (GO) improves outcomes with intensive chemotherapy in some adults with acute myeloid leukemia (AML), but it has remained unclear which dosing schedule of GO is best. Here, we conducted a phase 1/2 study in 66 adults with newly diagnosed AML or other high-grade myeloid neoplasm, and found that a fractionated dosing schedule of GO (GO3) can be safely combined with cladribine, high-dose cytarabine, G-CSF, and dose-escalated mitoxantrone (CLAG-M). Fifty-two out of sixty (87%) patients treated with CLAG-M/GO3 achieved a complete remission (CR)/CR with incomplete hematologic recovery (CRi), 45/52 (87%) without flow cytometric measurable residual disease. Six- and twelve-month event-free survival were 73% and 58%; among favorable-risk patients, these estimates were 100% and 95%. Compared to 186 medically matched adults treated with CLAG-M alone, CLAG-M/GO3 was associated with better survival in patients with favorable-risk disease. These data indicate that CLAG-M/GO3 is safe and more efficacious than CLAG-M alone in favorable-risk AML/high-grade myeloid neoplasm. Gemtuzumab ozogamicin (GO) improves outcomes when added to intensive AML chemotherapy. A meta-analysis suggested the greatest benefit when combining fractionated doses of GO (GO3) with 7 + 3. To test whether GO3 can be safely used with high intensity chemotherapy, we conducted a phase 1/2 study of cladribine, high-dose cytarabine, G-CSF, and dose-escalated mitoxantrone (CLAG-M) in adults with newly diagnosed AML or other high-grade myeloid neoplasm (NCT03531918). Sixty-six patients with a median age of 65 (range: 19–80) years were enrolled. Cohorts of six and twelve patients were treated in phase 1 with one dose of GO or three doses of GO (GO3) at 3 mg/m2 per dose. Since a maximum-tolerated dose was not reached, the recommended phase 2 dose (RP2D) was declared to be GO3. At RP2D, 52/60 (87%) patients achieved a complete remission (CR)/CR with incomplete hematologic recovery (CRi), 45/52 (87%) without flow cytometric measurable residual disease (MRD). Eight-week mortality was 0%. Six- and twelve-month event-free survival (EFS) were 73% and 58%; among favorable-risk patients, these estimates were 100% and 95%. Compared to 186 medically matched adults treated with CLAG-M alone, CLAG-M/GO3 was associated with better survival in patients with favorable-risk disease (EFS: p = 0.007; OS: p = 0.030). These data indicate that CLAG-M/GO3 is safe and leads to superior outcomes than CLAG-M alone in favorable-risk AML/high-grade myeloid neoplasm.
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急性髓样白血病患者中添加了gemtuzumab ozogamicin将其诱导化疗：从随机对照试验中对单个患者数据的荟萃分析。
DOI：
10.1016/s1470-2045(14)70281-5
发表时间：
2014-08
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Hills RK;Castaigne S;Appelbaum FR;Delaunay J;Petersdorf S;Othus M;Estey EH;Dombret H;Chevret S;Ifrah N;Cahn JY;Récher C;Chilton L;Moorman AV;Burnett AK
通讯作者：
Burnett AK
影响因子：
13.5
作者：
MCDONALD, GB;SHARMA, P;THOMAS, ED
通讯作者：
THOMAS, ED
影响因子：
45.3
作者：
Walter, Roland B.;Othus, Megan;Estey, Elihu H.
通讯作者：
Estey, Elihu H.
影响因子：
45.3
作者：
Burnett, Alan K.;Hills, Robert K.;Wheatley, Keith
通讯作者：
Wheatley, Keith
影响因子：
45.3
作者：
Schlenk, Richard F.;Paschka, Peter;Doehner, Hartmut
通讯作者：
Doehner, Hartmut