埃罗妥珠单抗联合泊马度胺和地塞米松治疗多发性骨髓瘤。

Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma.

机构信息

From the National and Kapodistrian University of Athens, Athens (M.A.D.); Karol Marcinkowski University of Medical Sciences, Poznań (D.D.), and Silesian Medical University, Katowice (S.G.) - both in Poland; University Hospital, Nantes (P.M.), and Centre Hospitalier Universitaire de Poitiers-La Milétrie, Poitiers (X.L.) - both in France; National Hospital Organization Disaster Medical Center (N.T.) and the Japanese Red Cross Medical Center (K.S.), Tokyo, and Ibaraki Prefectural Central Hospital, Kasama (M.H.) - all in Japan; Hôpital Maisonneuve-Rosemont, University of Montreal, Montreal (R.L.); Heidelberg University Hospital, Heidelberg, Germany (M.S.R.); Dana-Farber Cancer Institute, Boston (P.G.R.); Bristol-Myers Squibb, Princeton, NJ (M.P.M., Y.-M.J., S.G.S., M.R., B.R.); and Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada, Instituto de Investigación Sanitaria de Navarra (IDISNA), Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Pamplona, Spain (J.S.-M.).

出版信息

N Engl J Med. 2018 Nov 8;379(19):1811-1822. doi: 10.1056/NEJMoa1805762.

DOI:10.1056/NEJMoa1805762

PMID:30403938

Abstract

BACKGROUND

The immunostimulatory monoclonal antibody elotuzumab plus lenalidomide and dexamethasone has been shown to be effective in patients with relapsed or refractory multiple myeloma. The immunomodulatory agent pomalidomide plus dexamethasone has been shown to be effective in patients with multiple myeloma that is refractory to lenalidomide and a proteasome inhibitor.

METHODS

Patients with multiple myeloma that was refractory or relapsed and refractory to lenalidomide and a proteasome inhibitor were randomly assigned to receive elotuzumab plus pomalidomide and dexamethasone (elotuzumab group) or pomalidomide and dexamethasone alone (control group). The primary end point was investigator-assessed progression-free survival.

RESULTS

A total of 117 patients were randomly assigned to the elotuzumab group (60 patients) or the control group (57 patients). After a minimum follow-up period of 9.1 months, the median progression-free survival was 10.3 months in the elotuzumab group and 4.7 months in the control group. The hazard ratio for disease progression or death in the elotuzumab group as compared with the control group was 0.54 (95% confidence interval [CI], 0.34 to 0.86; P=0.008). The overall response rate was 53% in the elotuzumab group as compared with 26% in the control group (odds ratio, 3.25; 95% CI, 1.49 to 7.11). The most common grade 3 or 4 adverse events were neutropenia (13% in the elotuzumab group vs. 27% in the control group), anemia (10% vs. 20%), and hyperglycemia (8% vs. 7%). A total of 65% of the patients in each group had infections. Infusion reactions occurred in 3 patients (5%) in the elotuzumab group.

CONCLUSIONS

Among patients with multiple myeloma in whom treatment with lenalidomide and a proteasome inhibitor had failed, the risk of progression or death was significantly lower among those who received elotuzumab plus pomalidomide and dexamethasone than among those who received pomalidomide plus dexamethasone alone. (Funded by Bristol-Myers Squibb and AbbVie Biotherapeutics; ELOQUENT-3 ClinicalTrials.gov number, NCT02654132 .).

摘要

背景

免疫刺激单克隆抗体依鲁替尼联合来那度胺和地塞米松已被证明对复发性或难治性多发性骨髓瘤患者有效。免疫调节剂泊马度胺联合地塞米松已被证明对来那度胺和蛋白酶体抑制剂难治性多发性骨髓瘤患者有效。

方法

对来那度胺和蛋白酶体抑制剂难治或复发的多发性骨髓瘤患者进行随机分组，分别接受依鲁替尼联合泊马度胺和地塞米松（依鲁替尼组）或泊马度胺和地塞米松单药治疗（对照组）。主要终点为研究者评估的无进展生存期。

结果

共 117 例患者随机分配至依鲁替尼组（60 例）或对照组（57 例）。在 9.1 个月的最小随访期后，依鲁替尼组中位无进展生存期为 10.3 个月，对照组为 4.7 个月。依鲁替尼组疾病进展或死亡的风险比为 0.54（95%置信区间，0.34 至 0.86；P=0.008）。依鲁替尼组的总缓解率为 53%，对照组为 26%（优势比，3.25；95%置信区间，1.49 至 7.11）。最常见的 3 级或 4 级不良事件为中性粒细胞减少症（依鲁替尼组 13%，对照组 27%）、贫血（10%比 20%）和高血糖症（8%比 7%）。两组各有 65%的患者发生感染。依鲁替尼组有 3 例（5%）患者发生输注反应。

结论

在来那度胺和蛋白酶体抑制剂治疗失败的多发性骨髓瘤患者中，与接受泊马度胺联合地塞米松单药治疗的患者相比，接受依鲁替尼联合泊马度胺和地塞米松治疗的患者进展或死亡的风险显著降低。（由 Bristol-Myers Squibb 和 AbbVie Biotherapeutics 资助；ELOQUENT-3ClinicalTrials.gov 编号，NCT02654132）。