Gemtuzumab Ozogamicin Versus Best Supportive Care in Older Patients With Newly Diagnosed Acute Myeloid Leukemia Unsuitable for Intensive Chemotherapy: Results of the Randomized Phase III EORTC-GIMEMA AML-19 Trial
Gemtuzumab Ozogamicin Versus Best Supportive Care in Older Patients With Newly Diagnosed Acute Myeloid Leukemia Unsuitable for Intensive Chemotherapy: Results of the Randomized Phase III EORTC-GIMEMA AML-19 Trial
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DOI：
10.1200/jco.2015.64.0060
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发表时间：
2016-03-20
影响因子：
45.3
通讯作者：
Baron, Frederic
中科院分区：
文献类型：
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作者：
Amadori, Sergio;Suciu, Stefan;Baron, Frederic
目的比较单药吉妥珠单抗（GO）与最佳支持治疗（BSC）（包括羟基脲）作为不适合强化化疗的老年急性髓性白血病患者的一线治疗。1）接受GO（第1天6 mg/m2，第8天3 mg/m2）或BSC单次诱导疗程。GO诱导后没有进展的患者可以接受最多8个月的2 mg/m2免疫缀合物输注。随机化按年龄、WHO体能评分、CD 33表达状态和中心分层。主要终点为意向治疗分析的总生存期（OS）。结果共237例患者被随机分配（118例GO和119例BSC）。GO组的中位OS为4.9个月（95% CI，4.2至6.8个月），BSC组为3.6个月（95% CI，2.6至4.2个月）（风险比，0.69; 95% CI，0.53至0.90; P = 0.005）; GO组的1年OS率为24.3%，BSC组为9.7%。GO的OS获益在大多数亚组中一致，在CD 33高表达状态患者、细胞遗传学风险特征良好/中等的患者和女性中尤其明显。总体而言，111例GO受者中有30例（27%）出现完全缓解（CR [完全缓解] + CRi [外周血计数不完全恢复的CR]）。严重不良事件（AE）的发生率在两组相似，并没有额外的死亡率与GO。结论一线单药治疗低剂量GO，与BSC相比，显着改善OS在老年急性髓系白血病患者谁是不符合强化化疗。未发现非预期AE，毒性可管理。
Purpose To compare single-agent gemtuzumab ozogamicin (GO) with best supportive care (BSC) including hydroxyurea as first-line therapy in older patients with acute myeloid leukemia unsuitable for intensive chemotherapy.Patients and Methods In this trial, patients at least 61 years old were centrally randomized (1: 1) to receive either a single induction course of GO (6 mg/m(2) on day 1 and 3 mg/m(2) on day 8) or BSC. Patients who did not progress after GO induction could receive up to eight monthly infusions of the immunoconjugate at 2 mg/m(2). Randomization was stratified by age, WHO performance score, CD33 expression status, and center. The primary end point was overall survival (OS) by intention-to-treat analysis.Results A total of 237 patients were randomly assigned (118 to GO and 119 to BSC). The median OS was 4.9 months (95% CI, 4.2 to 6.8 months) in the GO group and 3.6 months (95% CI, 2.6 to 4.2 months) in the BSC group (hazard ratio, 0.69; 95% CI, 0.53 to 0.90; P =.005); the 1-year OS rate was 24.3% with GO and 9.7% with BSC. The OS benefit with GO was consistent across most subgroups, and was especially apparent in patients with high CD33 expression status, in those with favorable/intermediate cytogenetic risk profile, and in women. Overall, complete remission (CR [complete remission] + CRi [CR with incomplete recovery of peripheral blood counts]) occurred in 30 of 111 (27%) GO recipients. The rates of serious adverse events (AEs) were similar in the two groups, and no excess mortality from AEs was observed with GO.Conclusion First-line monotherapy with low-dose GO, as compared with BSC, significantly improved OS in older patients with acute myeloid leukemia who were ineligible for intensive chemotherapy. No unexpected AEs were identified and toxicity was manageable.