美国Atrium Health公司Saad Z Usmani小组比较了卡非佐米+地塞米松+达雷木单抗与卡非佐米+地塞米松治疗复发或难治性多发性骨髓瘤的效果。2020年7月18日，该研究发表在《柳叶刀》杂志上。

来那度胺和硼替佐米常用于一线治疗复发或难治性多发性骨髓瘤患者。在一项临床1期研究中，卡非佐米联合达雷木单抗治疗复发或难治性多发性骨髓瘤疗效显著，安全耐受。在这项研究中，研究组旨在比较卡非佐米+地塞米松+达雷木单抗与卡非佐米+地塞米松治疗复发或难治性多发性骨髓瘤患者的疗效和安全性。主要终点为无进展生存期。

在这项随机、多中心、开放标签的临床3期研究中，2017年6月13日至2018年6月25日，研究组从北美、欧洲、澳大利亚和亚洲的102个地区招募了466例复发或难治性多发性骨髓瘤患者，将其按2：1随机分组，分别接受卡非佐米+地塞米松+达雷木单抗（KdD）或卡非佐米+地塞米松（Kd）治疗。

中位随访约17个月后，KdD组未达到中位无进展生存期，而Kd组则为15.8个月，风险比为0.63。KdD组的中位治疗持续时间为70.1周，显著长于Kd组（40.3周）。KdD组中有82％的患者发生了3级及以上不良事件，Kd组中有74%。KdD组中有22%的患者因不良事件而终止治疗，Kd组有25%，两组相差不大。

总之，对于复发或难治性多发性骨髓瘤患者，采用KdD方案治疗，与Kd方案相比，可显著延长无进展生存期，患者可临床获益。

附：英文原文

Title: Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study

Author: Meletios Dimopoulos, Hang Quach, Maria-Victoria Mateos, Ola Landgren, Xavier Leleu, David Siegel, Katja Weisel, Hui Yang, Zandra Klippel, Anita Zahlten-Kumeli, Saad Z Usmani

Issue&Volume: 2020/07/18

Abstract: Background

Lenalidomide and bortezomib frontline exposure has raised a growing need for novel treatments for patients with relapsed or refractory multiple myeloma. Carfilzomib in combination with daratumumab has shown substantial efficacy with tolerable safety in relapsed or refractory multiple myeloma in a phase 1 study. In this study, we aimed to compare the efficacy and safety of carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma.

Methods

In this randomised, multicentre, open-label, phase 3 study, 466 patients recruited from 102 sites across North America, Europe, Australia, and Asia with relapsed or refractory multiple myeloma were randomly assigned 2:1 to carfilzomib, dexamethasone, and daratumumab (KdD) or carfilzomib and dexamethasone (Kd). All patients received twice per week carfilzomib at 56 mg/m 2 (20 mg/m 2; days 1 and 2 during cycle 1). Daratumumab (8 mg/kg) was administered intravenously on days 1 and 2 of cycle 1 and at 16 mg/kg weekly for the remaining doses of the first two cycles, then every 2 weeks for four cycles (cycles 3–6), and every 4 weeks thereafter. Patients received 40 mg dexamethasone weekly (20 mg for patients ≥75 years old starting on the second week). The primary endpoint was progression-free survival assessed by intention to treat. Adverse events were assessed in the safety population. This trial ( NCT03158688) is registered with ClinicalTrials.gov, and is active but not recruiting.

Findings

Between June 13, 2017, and June 25, 2018, 466 patients of 569 assessed for eligibility were enrolled. After median follow-up of approximately 17 months, median progression-free survival was not reached in the KdD group versus 15·8 months in the Kd group (hazard ratio 0·63; 95% CI 0·46–0·85; p=0·0027). Median treatment duration was longer in the KdD versus the Kd group (70·1 vs 40·3 weeks). Grade 3 or higher adverse events were reported in 253 (82%) patients in the KdD group and 113 (74%) patients in the Kd group. The frequency of adverse events leading to treatment discontinuation was similar in both groups (KdD, 69 [22%]; Kd, 38 [25%]).

Interpretation

KdD significantly prolonged progression-free survival versus Kd in patients with relapsed or refractory multiple myeloma and was associated with a favourable benefit–risk profile.

DOI: 10.1016/S0140-6736(20)30734-0

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30734-0/fulltext