Abstract
BackgroundMany clinical trials have assessed the effect and safety of monoclonal antibodies (MAbs) in combination with proteasome inhibitors or immunomodulators plus dexamethasone/prednisone for the treatment of multiple myeloma (MM). The treatment outcomes of comparing different MAbs in combination with the above-mentioned agents remained unclear. We performed the meta-analysis to indirectly compare the effect and safety of MAbs targeting CD38, SLAMF7, and PD-1/PD-L1 in combination with bortezomib/immunomodulators plus dexamethasone/prednisone for patients with MM.MethodsWe searched thoroughly in the databases for randomised controlled trials (RCTs) in which at least one of the three MAbs were included. We included eleven eligible RCTs with 5367 patients in the meta-analysis. Statistical analysis was carried out using StataMP14 and Indirect Treatment Comparisons software.ResultsWe calculated hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and relative risk (RR) for overall response rate, complete response (CR) or better, very good partial response (VGPR) or better, VGPR, partial response, stable disease, and grade 3 or higher adverse events among the three groups. The HRs for PFS of the CD38 group vs SLAMF7 group, CD38 group vs PD-1/PD-L1 group, and SLAMF7 group vs PD-1/PD-L1 group were 0.662 (95%CI 0.543–0.806), 0.317 (95%CI 0.221–0.454), and 0.479 (95%CI 0.328–0.699), respectively. The HR for OS of the CD38 group vs SLAMF7 group was 0.812 (95%CI 0.584–1.127). The RR for CR or better in the CD38 group vs SLAMF7 group was 2.253 (95%CI 1.284–3.955). The RR for neutropenia of the CD38 group vs SLAMF7 group was 1.818 (95%CI 1.41–2.344).ConclusionsTreatment with the CD38 group had longer PFS and better treatment response than that with the SLAMF7 or PD-1/PD-L1 group. In addition, the SLAMF7 group prolonged PFS compared with the PD-1/PD-L1 group and was associated with a lower incidence of grade 3 or higher neutropenia than the CD38 and PD-1/PD-L1 group. In conclusion, MAbs targeting CD38 are the best, followed by those targeting SLAMF7; MAbs targeting PD-1/PD-L1 are the worst when in combination with bortezomib/immunomodulators plus dexamethasone/prednisone for the treatment of MM.
Highlights
Many clinical trials have assessed the effect and safety of monoclonal antibodies (MAbs) in combination with proteasome inhibitors or immunomodulators plus dexamethasone/prednisone for the treatment of multiple myeloma (MM)
The SLAMF7 group prolonged progression-free survival (PFS) compared with the PD-1/programmed cell death ligand 1 (PD-L1) group and was associated with a lower incidence of grade 3 or higher neutropenia than the cluster of differentiation 38 (CD38) and PD-1/PD-L1 group
The cluster of differentiation 38 (CD38) protein is a enzyme with multiple functions including degrading nicotinamide adenine dinucleotide (NAD) and regulating cellular NAD homeostasis; it has been discovered that CD38 was a cell surface marker of hematological malignancies such as MM [2]
Summary
Many clinical trials have assessed the effect and safety of monoclonal antibodies (MAbs) in combination with proteasome inhibitors or immunomodulators plus dexamethasone/prednisone for the treatment of multiple myeloma (MM). We performed the meta-analysis to indirectly compare the effect and safety of MAbs targeting CD38, SLAMF7, and PD-1/PD-L1 in combination with bortezomib/immunomodulators plus dexamethasone/ prednisone for patients with MM. Multiple Myeloma (MM) is a malignant plasma cell disease, which is the second most common malignancy in the hematological system. It accounted for 1% of all reported tumours and 13% of hematological cancers. The MAbs targeting the surface SLAMF7 glycoprotein of MM cells such as elotuzumab improved the prognosis of MM patients when administered in combination with proteasome inhibitors or
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