Randomized multicenter phase 2 study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma
Randomized multicenter phase 2 study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma
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DOI：
10.1182/blood-2015-11-682518
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发表时间：
2016-05-26
期刊：
影响因子：
20.3
通讯作者：
Jagannath, Sundar
中科院分区：
文献类型：
--
作者：
Baz, Rachid C.;Martin, Thomas G., III;Jagannath, Sundar
来那度胺和低剂量地塞米松（PomDex）是来那度胺难治性骨髓瘤患者既往接受bbb20治疗的标准治疗。我们的目的是评估在标准PomDex基础上每周口服环磷酰胺的安全性和有效性。我们首先进行了剂量递增的1期研究，以确定环磷酰胺联合PomDex的推荐2期剂量（a组）。随后进行了一项随机、多中心2期研究，纳入了来那度胺难治性骨髓瘤患者。患者随机（1:1）接受泊马度胺4mg，在28天周期的第1至21天联合每周一次地塞米松（B组）或泊马度胺、地塞米松和环磷酰胺（PomCyDex） 400mg，在第1、8和15天口服（C组）。主要终点为总有效率（ORR）。80例患者入组（10例在1期，70例在2期随机化：36例在b组，34例在C组）。B组和C组的ORR分别为38.9%（95%可信区间[CI]， 23-54.8%）和64.7% (95% CI, 48.6-80.8%) （P = 0.035）。截至2015年6月，70名随机患者中有62名进展。B组和C组的中位无进展生存期（PFS）分别为4.4个月（95% CI, 2.3-5.7）和9.5个月（95% CI, 4.6-14） （P = 0.106）。在来那度胺难治性多发性骨髓瘤患者中，PomCyDex联合治疗的ORR和PFS优于PomDex。该试验在www.clinicaltrials.gov上注册为#NCT01432600。
Pomalidomide and low-dose dexamethasone (PomDex) is standard treatment of lenalidomide refractory myeloma patients who have received >2 prior therapies. We aimed to assess the safety and efficacy of the addition of oral weekly cyclophosphamide to standard PomDex. We first performed a dose escalation phase 1 study to determine the recommended phase 2 dose of cyclophosphamide in combination with PomDex (arm A). A randomized, multicenter phase 2 study followed, enrolling patients with lenalidomide refractory myeloma. Patients were randomized (1: 1) to receive pomalidomide 4 mg on days 1 to 21 of a 28-day cycle in combination with weekly dexamethasone (arm B) or pomalidomide, dexamethasone, and cyclophosphamide (PomCyDex) 400 mg orally on days 1, 8, and 15 (arm C). The primary end point was overall response rate (ORR). Eighty patients were enrolled (10 in phase 1 and 70 randomized in phase 2: 36 to armB and 34 to arm C). The ORR was 38.9% (95% confidence interval [CI], 23-54.8%) and 64.7% (95% CI, 48.6-80.8%) for arms B and C, respectively (P = .035). As of June 2015, 62 of the 70 randomized patients had progressed. The median progression-free survival (PFS) was 4.4 (95% CI, 2.3-5.7) and 9.5 months (95% CI, 4.6-14) for arms B and C, respectively (P = .106). Toxicity was predominantly hematologic in nature but was not statistically higher in arm C. The combination of PomCyDex results in a superior ORR and PFS compared with PomDex in patients with lenalidomide refractory multiple myeloma. The trial was registered at www.clinicaltrials.gov as #NCT01432600.