Malignant Hematology Department, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Kimmel Cancer Center/Johns Hopkins University, Baltimore, MD, USA.
Cancer Med. 2021 Jan;10(2):447-453. doi: 10.1002/cam4.3608. Epub 2020 Dec 22.
The utility of the International Working Group (IWG) 2006 response criteria for myelodysplastic syndromes (MDS) as a surrogate endpoint for outcomes is unclear. We assessed the validity of the IWG 2006 response criteria in a large cohort of higher-risk MDS patients (pts) treated at centers from the MDS Clinical Research Consortium. The best overall response rate (ORR) by IWG 2006 criteria to first-line therapy among 597 evaluable pts was 38% and include complete response (CR) 16%, marrow CR (mCR) 2%, partial response (PR) 10%, hematological improvement (HI) 10%, stable disease (SD) 33%, and progressive disease (PD) 24%. CR was associated with a better overall survival (OS) compared to all other response groups (P < 0.001). Among 470 pts treated with hypomethylating agent (HMA) as first-line therapy, the overall Response Rate, defined as HI or better was 39%. The median OS from time of best response was 21 mo, 8 mo, 14 mo, 12 mo, 13 mo, and 8 mo for CR, mCR, PR, HI, SD, and PD, respectively (P < 0.001). We validated those results in a separate cohort of 539 higher-risk MDS pts treated at Moffitt Cancer Center who received first-line HMA therapy, particularly addressing the value of mCR and mCR+HI. mCR alone without HI, SD, and PD outcomes were inferior to CR, PR, mCR+HI, and HI. In conclusion, CR by IWG 2006 response criteria can be used as a surrogate endpoint for OS in higher-risk MDS pts. Any response associated with restoration of effective hematopoiesis is associated with better outcome.
国际工作组（IWG）2006 年骨髓增生异常综合征（MDS）反应标准作为结局替代终点的效用尚不清楚。我们评估了该标准在 MDS 临床研究联盟中心治疗的高危 MDS 患者（pts）大型队列中的有效性。597 例可评估 pts 中，按 IWG 2006 标准一线治疗的最佳总体缓解率（ORR）为 38%，包括完全缓解（CR）16%、骨髓完全缓解（mCR）2%、部分缓解（PR）10%、血液学改善（HI）10%、疾病稳定（SD）33%和疾病进展（PD）24%。与所有其他反应组相比，CR 与更好的总生存（OS）相关（P<0.001）。在 470 例接受低甲基化药物（HMA）作为一线治疗的 pts 中，定义为 HI 或更好的总体反应率为 39%。从最佳反应时间开始的中位 OS 分别为 21 个月、8 个月、14 个月、12 个月、13 个月和 8 个月，用于 CR、mCR、PR、HI、SD 和 PD（P<0.001）。我们在 Moffitt 癌症中心接受一线 HMA 治疗的另外 539 例高危 MDS pts 队列中验证了这些结果，特别是解决了 mCR 和 mCR+HI 的价值。没有 HI、SD 和 PD 结果的 mCR 单独，不如 CR、PR、mCR+HI 和 HI。总之，按 IWG 2006 反应标准的 CR 可用作高危 MDS pts OS 的替代终点。任何与有效造血恢复相关的反应都与更好的结果相关。
