来源：肿瘤资讯
老年APL患者的常规治疗为ATRA-蒽环类化疗（CT）疗法，近日ASH大会上法国比利时瑞士APL组报道（APL 2006试验）联合三氧化二砷（ATO）方案可以减少患者CT使用量，提高CR率，同时复发率没有任何增加（和可能的减少）。
【研究背景】
老年ALP患者的常规治疗为ATRA-蒽环类化疗（CT）的疗法，和年轻患者类似，治疗复发较少，但死亡率高（CR率为87.3％，10年CIR为9.3％，CR死亡率为21.7％，在我们以前的APL试验中年龄≥65岁的患者10年OS为58％; Blood 2010 ,115:1690）。
最近的结果显示，在标准风险APL组中，ATRA + ATO组合（无CT）与传统的ATRA+CT方案效果至少是类似的，而骨髓抑制较少（Lo Coco，NEJM 2014; Burnett，Lancet Oncol 2015），这为老年患者带来一个非常有吸引力的新的方法。然而，当我们开始APL 2006试验时，不用CT治疗APL可行性没有被证明。此外，在大多数国家，ATO也没有广泛用于APL一线治疗，ATO的应用还很有限。APL 2006研究的目的是将ATO与ATRA联合，用于70岁以上标准风险APL（基线WBC <10G / L）的患者中以期减少化疗（CT）的使用。
【研究方法】
在2006~2015年间，新诊的APL患者（pts）> 70岁，WBC <10G / L，接受ATRA 诱导治疗，45mg / m 2 / d直到完全缓解（CR），在第3、5、7天应用伊达比星（Ida）45mg / m 2 / d，Ida 9mg / m 2 / dx 3与ATO 0.1mg / kg / d的第一次结合过程在治疗的25天，ATO（相同时间表）与ATRA的第二次结合过程在15天后。随后2年期间间歇应用ATRA维持治疗，连续6 MP + MTX+15天ATO/3个月在维持治疗的第一年。
在2010年9月，纳入55例患者后，因为CR的死亡率仍然很高（10/51 CR pts）而未见复发，在第一个巩固周期，巩固CT减少到一天的Ida。
研究的主要终点：是从CR开始后的无事件生存（EFS）。该研究的结果戴上到2016年1月1日。
【研究结果】
该研究共包括123位患者，中位年龄为73.6岁（范围为70~88.4），男性占56％。 其中113名（92％）患者达到CR，4名（3％）为耐药性白血病，6名（5％）出现脓毒症早期死亡（n = 3）和多器官衰竭（n = 3）。
在113例的CR患者中，3例复发（5年累积复发发生率为2.9％），两组间无显著性差异（p = 0.10，Gray检测）。 14例（12％）患者死亡（n=4，p = 0.045，Fisher检测），这些患者的死亡原因为脓毒症（n = 2），出血（n = 1）和前列腺癌（n = 1）。患者的5年OS为80％（95％CI，73-88％），5年EFS为80％（95％CI，73-88％），按期无差异（p = 0.71和p = 0.80分别通过对数秩检验）。第一次巩固治疗后，该疗法中ANC> 1 G / L和血小板> 50G / I的平均时间为5.6天和4.0天（p <0.0001和p <0.0001）,巩固过程与骨髓抑制不相关。
【研究总结】
在具有标准风险APL的这些老年患者群体（> 70岁）中，加用ATO与我们以前的ATRA-CT方案相比：可以使CT使用量减少，并提高CR率，且复发率没有任何增加（和可能的减少）。当巩固CT减少到一天的Ida时，才能在CR方案中观察到死亡率有所降低。这进一步证明了ATO在那些必须避免骨髓抑制的患者群体中的价值。
原文
898 Arsenic Trioxide (ATO) and ATRA with Limited Chemotherapy (CT) in Newly Diagnosed Standard Risk APL in the Elderly. a Report By the French Belgian Swiss APL Group (APL 2006 trial)
Lionel Ades, MD, PhD1, Xavier Thomas, MD, PhD2, Agnès Guerci, MD, PhD3*, Arnaud Pigneux, MD4,5*, Norbert Vey6,7, Emmanuel Raffoux, MD8*, Sylvie Castaigne, MD, PhD9, Olivier Spertini10, Dominique Bron, MD, PhD11, Jean Pierre Marolleau, MD, PhD12, Gandhi Damaj, MD13, Dominique Bordessoule, MD, PhD14, Julie Lejeune15*, Sylvie Chevret16* and Pierre Fenaux, MD, PhD17
Background.
Treatment of APL in the elderly with conventional ATRA-anthracycline based CT regimens is associated, like in younger patients, with very few relapses, but high death rates (CR rate of 87.3%, 10-year CIR of 9.3%, 21.7% deaths in CR, and a 10-year OS of 58% in patients aged> 65 years in our previous APL trials ;Blood 2010 115:1690). Recent results have shown that, in standard risk APL, ATRA+ATO combinations (without CT) are at least as effective as classical ATRA + CT regimens while being less myelosuppressive (Lo Coco, NEJM 2014; Burnett, Lancet Oncol, 2015) thus constituting a very appealing approach for elderly patients. However, when our APL 2006 trial started, the feasibility of treatment of APL without CT was unknown. Furthermore, access to ATO still remains limited for frontline treatment of APL in most countries. We present results of APL 2006 trial, where we combined ATO to ATRA and reduced CT in patients aged older than 70 with standard risk APL (baseline WBC <10G/L).
Methods. Between 2006 and 2015, newly diagnosed APL patients (pts)>70 years with WBC <10 G/L received induction treatment with ATRA 45mg/m2/d until CR and Idarubicin (Ida) 9 mg/m2/d on days 3, 5 and 7, a first consolidation course with Ida 9 mg/m2/dx3 combined with ATO 0.1 mg/kg/d during 25 days, a second consolidation course with ATO (same schedule)and ATRA during 15 days, followed by maintenance during 2 years with intermittent ATRA continuous 6 MP + MTX, plus 15 days ATO cycles every 3 months during the first maintenance year. In Sept 2010, after inclusion of 55 patients, because mortality in CR was still high (10/51 CR pts) while no relapse was observed, consolidation CT was reduced to one day of Ida during the first consolidation cycle. The primary endpoint was event-free survival (EFS) from CR achievement. We present here results at the reference date of Jan, 1, 2016. Results. Median age of the 123 pts included (after excluding one diagnosis error) was 73.6 years (range 70-88.4), with 56 % males. 113 (92%) pts achieved CR, 4 (3%) had resistant leukemia, and 6 (5%) had early death from sepsis (n=3), and multiorgan failure (n=3). Of the 113 CR pts, 3 relapsed (5-year cumulative incidence of relapse of 2.9%), with no significant difference across periods (p= 0.10, Gray’s test). 14 (12%) patients died in CR, including 4/62 (4%) accrued after vs 10/51 (20%) before the amendment (p= 0.045, Fisher’s test). Causes of death in CR were sepsis (n=4 before and 2 after amendment), bleeding (n=5 before and 1 after), general deterioration (n=1 before) and prostate cancer (n=1 after). 5-year OS was 80% (95%CI, 73-88%) and 5-year EFS was 80% (95%CI, 73-88%), with no difference according to period (p=0.71 and p=0.80 by the log-rank test, respectively). Mean time to ANC>1 G/L and platelets> 50G/l after the first consolidation course was 16.2 and 11.9 days in the original vs 5.6 and 4.0 days in the amended protocol (p<0.0001 and p<0.0001), while the second consolidation course was not associated with myelosuppression.
Conclusion. In this very old patient population (>70 years) with standard risk APL, addition of ATO, that allowed reduction of the amount of CT administered, was associated with high CR rates, without any increase (and a possible reduction) in the relapse rate compared to our previous experience with ATRA–CT regimens. However, reduction of mortality in CR with this regimen was only seen when consolidation CT was reduced to one single day of Ida. This is further evidence of the role of ATO in a patient population in whom myelosuppression must be avoided.
Disclosures: Ades: Celgene, Takeda, Novartis, Astex: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Thomas: Pfizer: Consultancy. Pigneux: Agios: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria. Fenaux: Celgene, Novartis, Teva: Honoraria; Celgene, Janssen, Novartis, Astex, Teva: Research Funding.
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