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三联疗法最初用于治疗骨髓瘤，并且多种联合方案已被全世界广泛应用。一种新型联合包含了最近被批准的口服药物ixazomib，可作为一种骨髓瘤治疗选择。据研究人员说，该联合提供了很高的响应率，毒性可控，并且相关费用较合理。
Meletios A. Dimopoulos博士说，大多数应用广泛的三药联合包含了蛋白酶体抑制剂
在美国，硼替佐米/
最近，首个口服蛋白酶体抑制剂ixazomib已被批准可与来那度胺和地塞米松（IRd）联合应用。该三药联合是首个被批准用于
现在，另外一个三药联合方案——ixazomib、环磷酰胺和地塞米松（ICd）——已表现出可观的临床活性。
研究人员比较了该方案和其它方案用于临床中的费用。结果显示，ICd需花费约$1000/月，需就医一次；IRd需花费约$2000/月，需就医一次；VRd 约$2000/月，平均就医4次；CyBorD 约$1000/月，就医4次。
Dimopoulos教授说，ICd是首个全口服药物联合，可在家治疗，安全易耐受，费用合理，持续治疗可行，提高了响应质量。
ICd联合方案的新结果
2016 ASCO大会上，Martha Lacy医学博士报道了1/2期试验ICd联合方案的新结果。该研究分析了48名新诊断骨髓瘤患者，中位年龄64岁。
治疗方案：第1、8、15天，ixazomib 4 mg；第1、8、15、22天，地塞米松 40 mg；第1、8、15、22天，环磷酰胺 300或400 mg/m²。28天为1疗程。12疗程后，患者将继续接受ixazomib单药治疗。4疗程后允许干细胞采集。在12个月时，患者停用了环磷酰啊和地塞米松的治疗，继续接受ixazomib治疗，直至疾病进展。
Lacy博士注意到，中位响应持续时间为18.4个月，患者响应深度一直在提高。总体响应率为77%，12个月时总生存率为100%，12个月时无进展生存率为91%。整体上，77%的患者发生了3级以上毒性反应，并且71%的患者发生了3+级血液学毒性。仅2%的患者需降低ixazomib剂量。另外，研究中无患者死亡。毒性如骨髓抑制可以控制，并且与先前报道的ixazomib毒性相似。神经学毒性轻微，似乎并没有累积性。
易耐受，费用合理
Dimopoulos博士注意到，他的小组一直在研究ICd联合方案。去年的美国血液学年会（ASH）公布了2期试验结果。受试人群为年老患者（中位年龄，70岁），目的是明确新诊断移植合格患者的环磷酰胺剂量。结果显示，该方案表现出惊人的早期响应率。
接受300 mg/m²和400 mg/m²环磷酰胺的患者的完全响应率+部分响应率分别为28%和21%，总体响应率分别为78%和65%，完全响应率分别为10%和9%。
Dimopoulos博士说，延长治疗提高了响应治疗；较低剂量的环磷酰胺更易耐受，并且疗效相似。
2016 ASCO大会上报道的该项最新研究同时纳入了年老及年轻患者。另外他指出，接受ixazomib治疗后再进行移植的患者能够进行干细胞采集。
摘要原文
Background: Ixazomib (Ixa) is an oral proteasome inhibitor, approved for treatment of relapsed myeloma (MM) in combination with lenalidomide and dexamethasone (Dex). The combination of bortezomib with cyclophosphamide (Ctx) and Dex is an effective regimen for initial therapy of MM. The combination of Ixa, Ctx and Dex could provide an effective, all oral regimen for initial therapy of MM.
Methods: NDMM patients (pts) with measurable disease, adequate organ function, and an ECOG PS >=2 were enrolled. The primary objective of the phase 1 was to determine the MTD of Ctx that can be combined with Ixa and Dex. Pts received Ixa 4 mg on days 1, 8, 15, dex 40 mg days 1, 8, 15, 22 and cyclophosphamide 300 or 400 mg/m2 days 1, 8, 15, 22; cycles were 28 days. Patients could continue on ixa alone after 12 cycles. The phase 2 portion was designed to determine the complete plus very good partial response rate (>=VGPR) of ixazomib to be used in combination with cyclophosphamide and dexamethasone in ND MM.
Results: Fifty-one pts were accrued, 10 to phase 1 and 41 patients to the phase 2 part of the trial, 3 pts were ineligible and were excluded. The median age was 64.5 (41-88); 52% were male. High or intermediate risk FISH was seen in 29% pts. Two patients have died, median (range) follow up for live pts was 8.7 months (2.8-28.3). Nineteen pts continue on treatment; of the 29 who have gone off treatment, majority did so for stem cell transplant, 4 had disease progression. RP2D was 400 mg/m2 of cyclophosphamide weekly, the highest dose tested. Best confirmed response included a partial response or better in 78%, including a VGPR rate of 33%; 2 patients had CR. Response rate at 4-cycle was 71%; the median time to a PR was 1.84 months. Dose modification were mostly in ctx and dex arms; 23 and 13% respectively. A grade 3 or higher adverse events (AE), considered possibly related was seen in 73%. Most common AE included cytopenias, fatigue and GI side effects.
Conclusions: The combination of Ixa, Ctx and Dex is well tolerated with high response rates. It offers the opportunity to utilize a completely oral regimen, which also is less expensive compared with the lenalidomide combinations. Future studies should assess its efficacy against other proteasome inhibitor combinations.
医脉通编译自：New Triplet Therapy in Multiple Myeloma.Medscape.2016
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