Abstract：
OBJECTIVE: To characterize the impact of prior exposure and refractoriness to lenalidomide or proteasome inhibitors (PIs) on the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory multiple myeloma (RRMM).
METHODS: INSURE is a pooled analysis of adult RRMM patients who had received IRd in ≥2 line of therapy from three studies: INSIGHT MM, UVEA-IXA, and REMIX.
RESULTS: Overall, 391/100/68 were lenalidomide-naïve/-exposed/-refractory and 37/411/110 were PI-naïve/-exposed/-refractory. Median duration of therapy (DOT) was 15.3/15.6/4.7 months and median progression-free survival (PFS) was 21.6/25.8/5.6 months in lenalidomide-naïve/exposed/refractory patients. Median DOT and PFS in PI-naïve/exposed/refractory patients were 20.4/15.2/6.9 months and not reached/19.8/11.4 months, respectively. The proportion of lenalidomide-naïve/exposed/refractory patients in INSIGHT and UVEA-IXA who discontinued a study drug due to adverse events (AEs) was ixazomib, 31.6/28.2/28.0% and 18.6/6.7/10.5%; lenalidomide, 21.9/28.2/16.0% and 16.1/6.7/10.5%; dexamethasone, 18.4/20.5/16.0% and 10.6/0/10.5%, respectively. The proportion of PI-naïve/exposed/refractory patients in INSIGHT and UVEA-IXA who discontinued a study drug due to AEs was: ixazomib, 44.4/28.8/27.8% and 22.2/16.7/15.7%; lenalidomide, 33.3/22.0/19.4% and 16.7/15.9/11.8%; dexamethasone, 33.3/17.4/16.7% and 16.7/9.5/7.8%, respectively. REMIX AE discontinuation rates were unavailable.
CONCLUSIONS: IRd appeared to be effective in RRMM patients in routine clinical practice regardless of prior lenalidomide or PI exposure, with better outcomes seen in lenalidomide- and/or PI-nonrefractory versus refractory patients.
METHODS: INSURE is a pooled analysis of adult RRMM patients who had received IRd in ≥2 line of therapy from three studies: INSIGHT MM, UVEA-IXA, and REMIX.
RESULTS: Overall, 391/100/68 were lenalidomide-naïve/-exposed/-refractory and 37/411/110 were PI-naïve/-exposed/-refractory. Median duration of therapy (DOT) was 15.3/15.6/4.7 months and median progression-free survival (PFS) was 21.6/25.8/5.6 months in lenalidomide-naïve/exposed/refractory patients. Median DOT and PFS in PI-naïve/exposed/refractory patients were 20.4/15.2/6.9 months and not reached/19.8/11.4 months, respectively. The proportion of lenalidomide-naïve/exposed/refractory patients in INSIGHT and UVEA-IXA who discontinued a study drug due to adverse events (AEs) was ixazomib, 31.6/28.2/28.0% and 18.6/6.7/10.5%; lenalidomide, 21.9/28.2/16.0% and 16.1/6.7/10.5%; dexamethasone, 18.4/20.5/16.0% and 10.6/0/10.5%, respectively. The proportion of PI-naïve/exposed/refractory patients in INSIGHT and UVEA-IXA who discontinued a study drug due to AEs was: ixazomib, 44.4/28.8/27.8% and 22.2/16.7/15.7%; lenalidomide, 33.3/22.0/19.4% and 16.7/15.9/11.8%; dexamethasone, 33.3/17.4/16.7% and 16.7/9.5/7.8%, respectively. REMIX AE discontinuation rates were unavailable.
CONCLUSIONS: IRd appeared to be effective in RRMM patients in routine clinical practice regardless of prior lenalidomide or PI exposure, with better outcomes seen in lenalidomide- and/or PI-nonrefractory versus refractory patients.
摘要：
目的：研究来那度胺或蛋白酶体抑制剂（PIs）的既往暴露和难治性对Ixazomib-来那度胺-地塞米松（IRd）治疗复发/难治性多发性骨髓瘤（RRMM）的有效性和安全性的影响。
方法：INSURE是对接受IRd≥2行治疗的成人RRMM患者的汇总分析，来自三项研究：INSIGHTMM，UVEA-IXA,和REMIX。
结果：总体而言，391/100/68是来那度胺-初始/-暴露/-难治性和37/411/110是PI-初始/-暴露/-难治性。来那度胺未治疗/暴露/难治性患者的中位治疗持续时间（DOT）为15.3/15.6/4.7个月，中位无进展生存期（PFS）为21.6/25.8/5.6个月。PI初治/暴露/难治性患者的DOT和PFS中位数为20.4/15.2/6.9个月，未达到/19.8/11.4个月，分别。INSIGHT和UVEA-IXA中来那度胺未治疗/暴露/难治性患者因不良事件（AE）而停用研究药物的比例为伊沙佐米，31.6/28.2/28.0%和18.6/6.7/10.5%；来那度胺，21.9/28.2/16.0%和16.1/6.7/10.5%；地塞米松，18.4/20.5/16.0%和10.6/0/10.5%，分别。在INSIGHT和UVEA-IXA中，因不良事件而停用研究药物的患者比例为：艾沙佐米，44.4/28.8/27.8%和22.2/16.7/15.7%；来那度胺，33.3/22.0/19.4%和16.7/15.9/11.8%；地塞米松，33.3%/17.4/16.7%和16.7/9.5/7.8%，分别。REMIXAE停药率不可用。
结论：IRd在常规临床实践中似乎对RRMM患者有效，无论先前的来那度胺或PI暴露，与难治性患者相比，来那度胺和/或PI非难治性患者的结局更好。
方法：INSURE是对接受IRd≥2行治疗的成人RRMM患者的汇总分析，来自三项研究：INSIGHTMM，UVEA-IXA,和REMIX。
结果：总体而言，391/100/68是来那度胺-初始/-暴露/-难治性和37/411/110是PI-初始/-暴露/-难治性。来那度胺未治疗/暴露/难治性患者的中位治疗持续时间（DOT）为15.3/15.6/4.7个月，中位无进展生存期（PFS）为21.6/25.8/5.6个月。PI初治/暴露/难治性患者的DOT和PFS中位数为20.4/15.2/6.9个月，未达到/19.8/11.4个月，分别。INSIGHT和UVEA-IXA中来那度胺未治疗/暴露/难治性患者因不良事件（AE）而停用研究药物的比例为伊沙佐米，31.6/28.2/28.0%和18.6/6.7/10.5%；来那度胺，21.9/28.2/16.0%和16.1/6.7/10.5%；地塞米松，18.4/20.5/16.0%和10.6/0/10.5%，分别。在INSIGHT和UVEA-IXA中，因不良事件而停用研究药物的患者比例为：艾沙佐米，44.4/28.8/27.8%和22.2/16.7/15.7%；来那度胺，33.3/22.0/19.4%和16.7/15.9/11.8%；地塞米松，33.3%/17.4/16.7%和16.7/9.5/7.8%，分别。REMIXAE停药率不可用。
结论：IRd在常规临床实践中似乎对RRMM患者有效，无论先前的来那度胺或PI暴露，与难治性患者相比，来那度胺和/或PI非难治性患者的结局更好。
