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2016年6月3-7日，一年一度的美国临床肿瘤学会（American Society of Clinical Oncology，ASCO）年会将在芝加哥举办。一项摘要号为7507的新研究表明，将硼替佐米增加至苯达莫斯汀/利妥昔单抗（BR）方案中，明显提高了未经治的高危滤泡淋巴瘤患者的完全缓解率（CR）。

Andrew M. Evens医学博士说，虽然高肿瘤负荷滤泡淋巴瘤的治疗已经得到了发展，但发展仍然较慢。通常而言，大多数患者会复发，并难以治愈。

大会上，Evens博士报道了评估标准方案联合新药治疗未经治的高危滤泡淋巴瘤的2期试验结果。

该试验纳入236名未经治的高危I/II级或IIIa级滤泡淋巴瘤患者。患者随机接受6疗程BR，随后接受利妥昔单抗维持治疗2年；或6疗程BR+硼替佐米，随后利妥昔单抗维持治疗2年，来那度胺维持治疗1年。主要终点是完全缓解率（CR）。

对222名患者进行了CR分析，其中包括接受BR+硼替佐米治疗的85名患者和接受BR治疗的137名患者。研究人员对两个治疗进行了平衡，中位年龄约60岁。大多数患者的ECOG体能状态评分为0或1分；1/4的患者存在结外侵犯，约2/3的患者存在骨髓侵犯。约86%的患者完成了6个计划的诱导疗程。

BR+硼替佐米组和BR组的总响应率均为91%，而CR率分别为74%和58%，前治疗组明显高于后治疗组。

诱导治疗期间，2名患者死亡，其中1名死于阿片类药物过量，另1名死于进行性病变。在所有患者中，因疾病进展和治疗毒性中止治疗的比例不到10%。

一般情况下，患者对这些治疗方案均可耐受。最常见的3/4级毒性在两治疗组中大致相同，主要包括中性粒细胞减少症、血小板减少症、乏力、发热性中性粒细胞减少症和腹泻等。BR+硼替佐米组的3级感觉神经病变率更高（12% vs 1%）。Evens博士注意到，这大多发生于接受硼替佐米静脉给药的患者，而接受皮下给药的患者较少见。

Evens博士说，硼替佐米增加至BR中一线治疗高肿瘤负荷滤泡淋巴瘤看似安全可行。这项初步报告表明，BR+硼替佐米所带来的CR率明显高于BR。然而，存在的一个大问题是CR与生存究竟有何关系？我们将期待相关数据加以分析CR与预后之间潜在的联系。

另外，仍需进一步随访探讨来那度胺增加至利妥昔单抗维持治疗中对患者预后的影响。

更精细的相关研究正在筹划之中。Evens博士说，研究者已经收集了大多数患者的组织块、骨髓、PET正电子扫描以及3000多个外周血样本，将分析个体的单核苷酸多态性、最小残留病变以及潜在的测序等。

摘要原文：

Effect of bortezomib on complete remission (CR) rate when added to bendamustine-rituximab (BR) in previously untreated high-risk (HR) follicular lymphoma (FL): A randomized phase II trial of the ECOG-ACRIN Cancer Research Group (E2408).Abstract No:7507

Background: Treatment strategies to improve outcomes in HR FL are needed. E2408 tested whether bortezomib (V) improves the CR rate when added to standard BR induction in untreated HR FL and whether lenalidomide (len) improves remission duration when added to maintenance rituximab (MR).

Methods: Eligible pts had untreated HR grade I/II or IIIa FL. HR was defined as high tumor burden by GELF and/or FLIPI 3-5. Pts were randomized to 1 of 3 arms in a 1:2:2 ratio: A) BR x 6 followed by MR x 2 years (yrs) vs B) BVR x 6 (V 1.3 mg/m2 IV/SQ days 1, 4, 8, 11) then MR x 2 yrs vs C) BR x 6 then MR x 2 yrs + len 20 mg/day x 1 yr. Pts enrolled 1/11-5/15. Response was assessed by 2007 IWG criteria using PET/CT. This analysis reports on the first primary objective of CR rate with induction therapy (Tx) with arms A) + C) combined for induction comparison (90% power at 1-sided α of 0.15).

Results: Among 250 randomized HR FL pts, 28 were excluded for not starting Tx (n = 5), ineligibility (n = 8) or central pathology review (n = 15). Analyses are based on 222 pts (BVR n = 85 vs BR n = 137); the arms were well balanced. Among all pts, GELF was high 92%; FLIPI 3-5 55%; ECOG PS 0 = 55%, 1 = 42% and 2 = 3%; marrow involvement 55%; and stages II 7%, III 27% and IV 66%. 86% of all pts received 6 induction cycles without differences between arms. The overall response for BVR was 91% vs 90% for BR, while CR rates were 74% vs 58%, respectively (2-sided P= 0.016). Respective ‘off treatment’ reasons for BVR vs BR were progressive disease in 4% and 7% and toxicity in 6% and 4%. The most common grade 3-4 toxicities (n = 241) for BVR vs BR were neutropenia (35%/30%), sensory neuropathy (SN) (12%/1%), thrombocytopenia (10%/5%), fatigue (6%/7%), febrile neutropenia (3%/5%) and diarrhea (5%/1%); 91% of grade 3 SN occurred with IV bortezomib (grade 3 SN incidence: 14% IV vs 4% SQ, OR = 3.7, P= 0.2). During induction Tx, there were 3 deaths (2 due to disease), all on arm C.

Conclusions: This initial reportof E2408 for untreated HR FL shows that the CR rate for BVR induction Tx was significantly superior compared with BR. Continued follow up is needed to assess survival and if len added to MR improves outcomes. Clinical trial information: NCT01685008

会议专题》》》2016年ASCO年会专题报道