Mateos Maria-Victoria, Goldschmidt Hartmut, San-Miguel Jesus, Mikhael Joseph, DeCosta Lucy, Zhou Lifen, Obreja Mihaela, Blaedel Julie, Szabo Zsolt, Leleu Xavier
University Hospital Salamanca, Salamanca, Spain.
Heidelberg Medical University and National Center for Tumor Diseases, Heidelberg, Germany.
Hematol Oncol. 2018 Apr;36(2):463-470. doi: 10.1002/hon.2499. Epub 2018 Feb 15.
We performed analyses of the randomized phase 3 ASPIRE and ENDEAVOR trials to investigate the efficacy of carfilzomib among subgroups of relapsed or refractory multiple myeloma patients who had early or late disease relapse following initiation of the immediately prior therapy. In ASPIRE and ENDEAVOR, patients had received 1 to 3 prior lines of therapy. Patients in ASPIRE received carfilzomib, lenalidomide, and dexamethasone (KRd) or lenalidomide and dexamethasone (Rd), and patients in ENDEAVOR received carfilzomib and dexamethasone (Kd) or bortezomib and dexamethasone (Vd). Patients with relapse ≤1 year after initiating the most recent prior line of therapy were categorized as early relapsers, and patients with relapse after >1 year were categorized as late relapsers. The median progression-free survival (PFS) in ASPIRE for early relapsers was 21.4 months for KRd vs 10.7 months for Rd (hazard ratio [HR]: 0.714; 95% confidence interval [CI]: 0.508-1.004; P = 0.0257), and for late relapsers was 29.7 months for KRd vs 18.2 months for Rd (HR: 0.675; 95% CI: 0.533-0.854; P = 0.0005). The overall response rate (ORR) for early relapsers was 83.2% for KRd vs 54.8% for Rd, and for late relapsers was 89.0% for KRd vs 69.7% for Rd. The median PFS in ENDEAVOR (Kd vs Vd) for early relapsers was 13.9 months vs 5.7 months (HR: 0.598; 95% CI: 0.423-0.846; P = 0.0017), and for late relapsers was 22.2 months vs 10.2 months (HR: 0.486; 95% CI: 0.382-0.620; P < 0.0001). The ORR (Kd vs Vd) for early relapsers was 63.4% vs 49.1% and for late relapsers was 81.8% vs 66.8%. In conclusion, patients with relapsed or refractory multiple myeloma who received carfilzomib-containing regimens had improved PFS and ORR compared with control groups, regardless of whether they had an early or late relapse following the most recent prior therapy.
我们对随机3期ASPIRE和ENDEAVOR试验进行了分析，以研究卡非佐米在复发或难治性多发性骨髓瘤患者亚组中的疗效，这些患者在开始上一线治疗后出现早期或晚期疾病复发。在ASPIRE和ENDEAVOR试验中，患者此前接受过1至3线治疗。ASPIRE试验中的患者接受卡非佐米、来那度胺和地塞米松（KRd）或来那度胺和地塞米松（Rd）治疗，ENDEAVOR试验中的患者接受卡非佐米和地塞米松（Kd）或硼替佐米和地塞米松（Vd）治疗。在开始最近一线治疗后≤1年复发的患者被归类为早期复发者，在>1年之后复发的患者被归类为晚期复发者。在ASPIRE试验中，早期复发者接受KRd治疗的中位无进展生存期（PFS）为21.4个月，接受Rd治疗的为10.7个月（风险比[HR]：0.714；95%置信区间[CI]：0.508 - 1.004；P = 0.0257），晚期复发者接受KRd治疗的为29.7个月，接受Rd治疗的为18.2个月（HR：0.675；95% CI：0.533 - 0.854；P = 0.0005）。早期复发者的总体缓解率（ORR），KRd组为83.2%，Rd组为54.8%；晚期复发者中，KRd组为89.0%，Rd组为69.7%。在ENDEAVOR试验中（Kd与Vd对比），早期复发者的中位PFS，Kd组为13.9个月，Vd组为5.7个月（HR：0.598；95% CI：0.423 - 0.846；P = 0.0017），晚期复发者中，Kd组为22.2个月，Vd组为10.2个月（HR：0.486；95% CI：0.382 - 0.620；P < 0.0001）。早期复发者的ORR（Kd与Vd对比）为63.4%对49.1%，晚期复发者为81.8%对66.8%。总之，复发或难治性多发性骨髓瘤患者接受含卡非佐米方案治疗后，与对照组相比，无进展生存期和总体缓解率均有所改善，无论他们在最近一线治疗后是早期还是晚期复发。
