目的 ：评估达雷妥尤单抗（Daratumumab, Dara）为基础的疗法对一线治疗新诊断多发性骨髓瘤（NDMM）患者的疗效和预后影响。

方法 ：回顾性分析 2019年 6月至 2022年12 月于中国医学科学院血液病医院（血液学研究所）淋巴瘤科就诊的309例的NDMM患者，对照分析比较一线应用Dara为基础的疗法与标准三药诱导疗法分诱导治疗疗效、生存及微小残留病（MRD）阴性率的差异，探究Dara诱导治疗对NDMM患者疗效和预后的影响。

结果 ：（1）本研究共纳入309例NDMM患者，年龄58（51-65）岁, 男170（55.02%）例，女139例（44.98%）。78例（25.24%）患者接受Dara为基础的治疗，231例（74.76）患者接受标准三药诱导治疗，155例（50.16%）患者接受自体移植。诱导治疗4-6周期后总有效率（ORR）为96.40%（295/306），深度缓解［≥完全缓解（CR）］率为35.29%（108/306），非常好的部分缓解（VGPR）及以上为70.26%（205/306）。随访时间23.35 月(18.47, 30.50)，获得MRD阴性率175 例(56.63)，Dara治疗组中位无进展生存时间（PFS）未达到，标准治疗组中位无进展生存时间43.32个月；两组中位总生存时间（OS）均未达到。（2）一线接受自体造血干细胞移植（ASCT）治疗的NDMM患者中， Dara为基础治疗的患者53例，标准治疗组101例，Dara组诱导治疗CRR率、≥VGPR率显著优于标准对照组，P值分别为0.023（47.17%对28.71%）、＜0.01（84.91%对53.47%），ORR率无显著差异（96.23%对92.08%，P =0.517）；未接受ASCT治疗的Dara治疗组患者25例，标准治疗组130例，Dara组诱导治疗组CRR率、≥VGPR率显著优于标准对照组，P值分别为0.004（60.00%对30.00%）、0.031（92.00%对71.54%），ORR率无显著差异（96.23%对92.08%，P =0.517）。截止2023年8月，中位随访时间：38.3（3.4～100.4）月，两组间生存无统计学差异。所有Dara组mPFS、mOS均未达到；未行ASCT标准治疗组mPFS为45.0（41.38-NA）个月，mOS 未达到；标准治疗组mPFS为45.01（41.38-NA）个月，mOS 未达到。未接受移植组NDMM中Dara诱导治疗组MRD阴性率81.13%（43/53），标准方案诱导治疗组MRD阴性率42.57%（43/101）， P＜0.001；接受移植组NDMM中Dara诱导治疗组MRD阴性率84.00%（21/25），标准方案诱导治疗组MRD阴性率53.12%（68/130）， P=0.004。（3）将78例Dara治疗组患者与231例标准治疗组患者进行1:1倾向性评分匹配（PSM）诱导治疗后，未接受ASCT治疗患者中，Dara治疗组ORR率、CRR率、≥VGPR率显著优于标准对照组，P值分别为0.023（96.00%对92.00%）、0.003（48.00%对20.00%）、＜0.001（84.00%对52.00%）；接受ASCT治疗的患者ORR率均为100%，Dara组诱导治疗组CRR率、≥VGPR率显著优于标准对照组，P值分别为0.023（60.00%对28.00%）、0.002（92.00%对52.00%）。PSM匹配后，未接受移植组NDMM中Dara诱导治疗组MRD阴性率82.00%（41/50），标准方案诱导治疗组MRD阴性率48.00%（24/50）， P＜0.001；接受移植组NDMM中Dara诱导治疗组MRD阴性率56.00%（14/25），标准方案诱导治疗组MRD阴性率40.00%（10/25）， P=0.258。

结论 ：一线接受Dara为基础诱导治疗的NDMM患者具有显著的疗效和生存获益。

Objective: To evaluate the efficacy and prognostic impact of daratumumab (Dara)-based therapy in first-line treatment of patients with newly diagnosed multiple myeloma (NDMM).

Methods: A retrospective analysis was performed on 309 NDMM patients treated in the Lymphoma Department of the Hematology Hospital (Institute of Hematology), Chinese Academy of Medical Sciences from June 2019 to December 2022, and a comparative analysis was performed to compare the first-line application of Dara-based therapy with standard The three-drug induction therapy was divided into differences in induction therapy efficacy, survival and minimal residual disease (MRD) negative rate, and the impact of Dara induction therapy on the efficacy and prognosis of NDMM patients was explored.

Results: (1) This study included a total of 309 NDMM patients, aged 58 (51-65) years old, 170 (55.02%) males and 139 females (44.98%). 78 patients (25.24%) received Dara-based therapy, 231 patients (74.76) received standard three-drug induction therapy, and 155 patients (50.16%) received autologous transplantation. After 4-6 cycles of induction therapy, the overall response rate (ORR) was 96.40% (295/306), the deep remission [≥ complete remission (CR)] rate was 35.29% (108/306), and the very good partial response (VGPR) and above is 70.26% (205/306). The follow-up time was 23.35 months (18.47, 30.50), and the MRD negative rate was obtained in 175 cases (56.63). The median progression-free survival time (PFS) of the Dara treatment group was not reached, and the median progression-free survival time (PFS) of the standard treatment group was 43.32 months; both groups Median overall survival (OS) was not reached. (2) Among the NDMM patients who received autologous hematopoietic stem cell transplantation (ASCT) in the first line, 53 patients received Dara as the basic treatment and 101 patients were in the standard treatment group. The induction treatment CRR rate and ≥VGPR rate in the Dara group were significantly better than those in the standard control group. The P values were 0.023 (47.17% vs. 28.71%) and <0.01 (84.91% vs. 53.47%) respectively, and there was no significant difference in the ORR rate (96.23% vs. 92.08%, P =0.517); patients in the Dara treatment group who did not receive ASCT treatment 25 For example, there were 130 patients in the standard treatment group. The CRR rate and ≥VGPR rate of the induction treatment group in the Dara group were significantly better than those in the standard control group. The P values were 0.004 (60.00% vs. 30.00%) and 0.031 (92.00% vs. 71.54%) respectively. The ORR rate There was no significant difference (96.23% vs. 92.08%, P =0.517). As of August 2023, the median follow-up time was: 38.3 (3.4-100.4) months, and there was no statistical difference in survival between the two groups. The mPFS and mOS of all Dara groups were not reached; the mPFS of the standard treatment group without ASCT was 45.0 (41.38-NA) months, and the mOS was not reached; the mPFS of the standard treatment group was 45.01 (41.38-NA) months, and the mOS was not reached. Among the NDMM who did not receive transplantation, the MRD negative rate in the Dara induction therapy group was 81.13% (43/53), and the MRD negative rate in the standard protocol induction therapy group was 42.57% (43/101), P<0.001; among the NDMM in the transplantation group, the Dara induction therapy group The MRD negative rate was 84.00% (21/25), and the MRD negative rate in the standard induction therapy group was 53.12% (68/130), P=0.004. (3) After 1:1 propensity score matching (PSM) induction treatment of 78 patients in the Dara treatment group and 231 patients in the standard treatment group, among the patients who did not receive ASCT treatment, the ORR rate, CRR rate, and ≥VGPR of the Dara treatment group were The rate was significantly better than that of the standard control group, with P values of 0.023 (96.00% vs. 92.00%), 0.003 (48.00% vs. 20.00%), and <0.001 (84.00% vs. 52.00%) respectively; the ORR rates of patients receiving ASCT were all 100 %, the CRR rate and ≥VGPR rate of the induction therapy group in the Dara group were significantly better than those in the standard control group, with P values of 0.023 (60.00% vs. 28.00%) and 0.002 (92.00% vs. 52.00%) respectively. After PSM matching, the MRD negative rate in the Dara induction therapy group among NDMM who did not receive transplantation was 82.00% (41/50), and the MRD negative rate in the standard protocol induction therapy group was 48.00% (24/50), P<0.001; among the NDMM in the transplantation group The MRD negative rate in the Dara induction therapy group was 56.00% (14/25), and the MRD negative rate in the standard protocol induction therapy group was 40.00% (10/25), P=0.258.

Conclusion: First-line NDMM patients receiving Dara-based induction therapy have significant efficacy and survival benefits.