Page 105 - 中国全科医学2022-21

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2.Department of Cardiovascular Surgery，Qinghai University Affiliated Hospital，Xining 810000，China
*
Corresponding author：GENG Hui，Chief physician，Professor；E-mail：810097342@qq.com
【Abstract】 Background Multiple myeloma is a malignant disease in which plasma cells abnormally proliferate in
the bone marrow. Most patients may experience relapse/refractory and drug resistance with an unsatisfactory prognosis. CD38
monoclonal antibodies have been reported to achieve durable remission in patients with relapsed and refractory multiple myeloma
（RRMM）. Although phase Ⅱ and Ⅲ clinical trials of CD38 monoclonal antibodies for MM have been initiated，a meta-analysis
of these trials is lacking. Objective To systematically assess the efficacy and safety of CD38 monoclonal antibodies in RRMM，
providing a theoretical basis for clinical treatment of this disease. Methods Databases including SinoMed，CQVIP，CNKI，
Wanfang Data，Web of Science，PubMed，EMBase，and Cochrane Library were searched for randomized controlled trials（RCTs）
of CD38 monoclonal antibodies treating RRMM published from inception to November 2021. The experimental group：the CD38
monoclonal antibody and the compatible drug were applied；the control group：only the compatible drug or CD38 monoclonal
antibody （no other drug compatibility） was used. Treatment efficacy was assessed using overall response rate（ORR），
progression-free survival（PFS），≥ very good partial response（≥ VGPR），partial response（PR），≥ complete remission
（ ≥ CR），and minimal residual disease（MRD）. Treatment safety was assessed using non-hematological adverse events，
≥ grade 3 non-hematological adverse events，and hematological adverse events. The Cochrane Collaboration's tool for assessing
risk of bias was used for quality assessment. A Meta-analysis was performed using Review Manager 5.3 and Stata 15.0. Results
Eight RCTs were finally included，with a total of 2 821 patients（including 1 529 in the experimental group and 1 292 in the
control group）. Meta-analysis showed that：in terms of efficacy，the experimental group had higher ORR，longer mean PFS，
higher prevalence of ≥ VGPR，MRD and ≥ CR than the control group〔RR=1.28，95%CI（1.15，1.43），P<0.000 01；
HR=0.49，95%CI（0.39，0.62），P<0.000 01；RR=1.86，95%CI（1.53，2.27），P<0.000 01；RR=5.28，95%CI（2.80，
9.96），P<0.001；RR=2.57，95%CI（1.89，3.50），P<0.001〕. The experimental group also had lower prevalence of PR
〔RR=0.67，95%CI（0.53，0.86），P=0.002〕. In terms of safety，among the non-hematological adverse events occurred，
the incidences of upper respiratory tract infection，pneumonia，bronchitis，diarrhea，and back pain in the experimental group
were higher than those in the control group〔RR=1.55，95%CI（1.36，1.77），P<0.001；RR=1.34，95%CI（1.13，1.59），
P<0.001；RR=1.64，95%CI（1.07，2.51），P=0.02；RR=1.49，95%CI（1.33，1.68），P<0.001；RR=1.29，95%CI
（1.07，1.57），P=0.009〕. Among the non-hematological adverse events of ≥ grade 3，the incidences of upper respiratory
tract infection，pneumonia，diarrhea，and fatigue in the experimental group were higher〔RR=1.99，95%CI（1.15，3.43），
P=0.01；RR=1.30，95%CI（1.05，1.62），P=0.02；RR=2.44，95%CI（1.58，3.76），P<0.001；RR=1.75，95%CI（1.19，
2.56），P=0.004〕. Among the hematological adverse events，the incidence of thrombocytopenia in the experimental group
was also higher〔RR=1.10，95%CI（1.01，1.20），P=0.02〕. Conclusion CD38 monoclonal antibodies may achieve good
overall efficacy in RRMM，in particular，the PFS was significantly prolonged，although risks of treatment-emergent pulmonary
infection，diarrhea，and thrombocytopenia may increase，the risks are controllable. To sum up，it is feasible to apply CD38
monoclonal antibodies for RRMM patient population，but be prepared to deal with high-risk complications.
【Key words】 Multiple myeloma；Hematologic neoplasms；Antineoplastic agents，immunological；Treatment
outcome；Safety；Drug-related side effects and adverse reactions；Meta analysis

多发性骨髓瘤（multiple myeloma，MM）是一种克隆性浆 择。在正常生理条件下，CD38 在免疫细胞上的表达水平特别
细胞异常增殖的恶性疾病。相关流行病学资料显示，MM 约 低 ［3］ ，但在 MM 患者的浆细胞表面 CD38 受体表达水平明显
占全世界所有癌症的 1%，占所有血液肿瘤的 10%~15% ［1］ ， 升高 ［4-5］ 。CD38 可以作为黏附受体，引导浆细胞进入骨髓
在很多国家其是血液系统第 2 位恶性肿瘤，多发生于老年 腔 ［6］ ，这是治疗 RRMM 的一个具有吸引力的靶点。本研究
人 ［2］ 。虽然 MM 患者经过治疗可缓解疾病进展、延长生存 所纳入的CD38单克隆抗体包括达雷妥尤单抗（Daratumumab）、
期，但目前仍然是无法治愈的，绝大多数患者可能会面临复 伊沙妥昔单抗（Isatuximab）两种。目前关于 CD38 单克隆抗
发及耐药的问题，预后不容乐观。MM 的治疗方案由最初的 体治疗 MM 患者的研究较多见。但关于 CD38 单克隆抗体在
马法兰、糖皮质激素、蒽环类等化疗药物转换为新的免疫调 RRMM 患者中应用的研究较少，故本研究通过 Meta 分析系统
节剂（如沙利度胺、来那度胺）、蛋白酶体抑制剂〔如硼替 评价 CD38 单克隆抗体治疗 RRMM 的疗效和安全性，以期为
佐米（Bortezomib）、卡菲佐米（Carfilzomib）〕、细胞免疫 临床治疗 RRMM 患者提供更多的理论依据。
治疗方法（CAR-T）和自体造血干细胞移植（ASCT）。随着 1 资料与方法
多种单克隆抗体药物的出现，复发 / 难治性 MM（relapsedand 1.1 文献检索策略 计算机检索中国生物医学文献服务系统
refractory multiple myeloma，RRMM）患者的治疗有了新的选 （SinoMed）、 维 普 网（CQVIP）、 中 国 知 网（CNKI）、 万