Objective: To compare the clinical efficacy, survival, and prognosis of autologous hematopoietic stem cell transplantation (ASCT) with new drug chemotherapy in the treatment of newly diagnosed multiple myeloma (NDMM) in the new drug era.
Methods: The clinical data of 149 patients with NDMM treated with new drug induction regimen in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2012 to December 2019 were retrospectively analyzed. Twenty-four patients who received ASCT were in ASCT group, and 125 patients who did not receive ASCT were in non-ASCT group. The median follow-up time was 43 (1-90) months. The propensity score matching (PSM) method was used to balance confounding factors, then depth of response, overall survival (OS), and progression-free survival (PFS) between the two groups were compared and subgroup analysis was performed.
Results: After matching, the covariates were balanced between the two groups. Fifty-one patients (15 cases in ASCT group and 36 cases in non-ASCT group) were included. ASCT patients had a better complete response (CR) rate than non-ASCT patients receiving maintenance therapy (93.3% vs 42.3%, P=0.004), while there were no statistical differences in deep response rate and overall response rate (ORR) between the two groups (93.3% vs 65.4%, P=0.103; 93.3% vs 96.2%, P=1.000). Before matching, the 3 and 5-year PFS rate and median PFS (mPFS) in ASCT group and non-ASCT group were [89.6% vs 66.5%, P=0.024; 69.8% vs 42.7%; non-response (NR) vs 51.0 months], and the 3 and 5-year OS rate and median OS (mOS) were (100% vs 70.6%, P=0.002; 92.3% vs 49.6%; NR vs 54.0 months). After matching, the 3 and 5-year PFS rate and mPFS in ASCT group and non-ASCT group were (83.6% vs 61.7%, P=0.182; 62.7% vs 45.7%; NR vs 51.0 months), the 3 and 5-year OS rate and mOS were (100% vs 65.6%, P=0.018; 88.9% vs 46.9%; NR vs 51.0 months). Subgroup analysis showed that patients with mSMART 3.0 high risk stratification, the 3-year PFS rate and mPFS in ASCT group and non-ASCT group were (83.3% vs 41.5%, P=0.091; NR vs 34.0 months), and the 3-year OS rate and mOS were (100% vs 41.5%, P=0.034; NR vs 34.0 months). Patients with mSMART 3.0 standard risk stratification, the 3-year PFS rate and OS rate in ASCT group and non-ASCT group were (83.3% vs 76.8%, P=0.672; 100% vs 87.2%, P=0.155). The 3-year PFS and OS rate in MM patients who achieved deep response within 3 months after transplantation compared with non-ASCT patients who achieved deep response after receiving maintenance therapy were (83.1% vs 56.7%, P=0.323; 100% vs 60.5%, P=0.042), and the 3-year PFS and OS rate in patients who achieved overall response in both groups were (83.1% vs 62.5%, P=0.433; 100% vs 68.1%, P=0.082). After matching, Cox multivariate regression analysis showed that mSMART 3.0 risk stratification and ASCT were independent prognostic factors for OS.
Conclusion: In the new drug era, ASCT can increase CR rate and prolong OS of NDMM patients. ASCT patients who are mSMART 3.0 high risk stratification or achieved deep response within 3 months after transplantation have better OS than non-ASCT patients receiving new drug chemotherapy. ASCT and mSMART 3.0 risk stratification are independent prognostic factors for OS in NDMM patients.
题目: 自体造血干细胞移植与新药化疗治疗新诊断多发性骨髓瘤的倾向性评分匹配研究.
目的: 比较新药时代自体造血干细胞移植（ASCT）和新药化疗治疗新诊断多发性骨髓瘤（NDMM）的临床疗效、生存期及预后分析.
方法: 回顾性分析2012年1月至2019年12月华中科技大学同济医学院附属协和医院采用新药方案诱导化疗的149例NDMM患者的临床资料，24例接受ASCT的患者为移植组，125例未接受ASCT的患者为非移植组，中位随访时间43（1-90）个月。采用倾向性评分匹配法均衡组间混杂因素后比较组间缓解深度、总生存时间（OS）、无进展生存时间（PFS），并进行亚组分析.
结果: 通过匹配组间的协变量达到均衡，51例患者进入研究，移植组15例，非移植组36例。匹配后，移植组完全缓解（CR）率较非移植组接受维持治疗的CR率高（93.3% vs 42.3%，P=0.004），而深度缓解率和总有效率差异均无统计学意义（93.3% vs 65.4%，P=0.103；93.3% vs 96.2%，P=1.000）。匹配前，移植组较非移植组3、5年的PFS率和中位无进展生存时间（mPFS）分别为（89.6% vs 66.5%，P=0.024；69.8% vs 42.7%；未达到 vs 51.0个月），3、5年OS率和中位OS（mOS）分别为（100% vs 70.6%，P=0.002；92.3% vs 49.6%；未达到 vs 54.0个月）；匹配后，移植组较非移植组3、5年PFS率和mPFS分别为（83.6% vs 61.7%，P=0.182；62.7% vs 45.7%；未达到 vs 51.0个月），3、5年OS率和mOS分别为（100% vs 65.6%，P=0.018；88.9% vs 46.9%；未达到 vs 51.0个月）。亚组分析显示，mSMART 3.0危险分层高危患者中，移植组较非移植组3年PFS率、mPFS为（83.3% vs 41.5%，P=0.091；未达到 vs 34.0个月），3年OS率、mOS分别为（100% vs 41.5%，P=0.034；未达到 vs 34.0个月）。mSMART 3.0危险分层标危患者中，移植组较非移植组3年PFS率和OS率分别为（83.3% vs 76.8%，P=0.672；100% vs 87.2%，P=0.155）。移植后3个月内疗效获深度缓解组较接受维持治疗的非移植患者达深度缓解组3年PFS和OS率为 （83.1% vs 56.7%，P=0.323；100% vs 60.5%，P=0.042），两组疗效达总有效缓解的3年PFS和OS率为（83.1% vs 62.5%，P=0.433；100% vs 68.1%，P=0.082）。匹配后COX多因素回归分析显示，mSMART 3.0危险分层标危、ASCT是改善NDMM患者OS的预后因素.
结论: 在新药时代，ASCT治疗较新药化疗提高了NDMM患者的CR率、延长了OS。接受自体移植的mSMART 3.0高危、疗效达深度缓解的患者相较接受新药化疗的非移植患者OS获益。mSMART 3.0危险分层、自体移植是NDMM患者OS的独立预后因素.
Keywords: autologous hematopoietic stem cell transplantation; multiple myeloma; new drug era; propensity matching analysis; survival time.