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 Ⅱand Ⅲclinical 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.
