Isatuximab-based Therapy for Newly Diagnosed Multiple Myeloma: a Systematic Review and Meta-analysis
Year: 2026
Type: article
Study designs: Systematic Review, Meta-Analysis
Abstract: Background Isatuximab, an anti-CD38 monoclonal antibody, has demonstrated promising efficacy in newly diagnosed multiple myeloma. However, evidence regarding its effects on treatment response, progression-free survival, stem-cell mobilization, and safety remains limited. This systematic review and meta-analysis evaluated the efficacy and safety of isatuximab-based therapy in patients with newly diagnosed multiple myeloma. Methods A PRISMA-compliant systematic review and meta-analysis was conducted. PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library were systematically searched from inception. Seven studies involving 2,626 patients with newly diagnosed multiple myeloma were included. Random-effects meta-analyses were performed to estimate pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) for efficacy and safety outcomes. Results Isatuximab-based therapy demonstrated consistent efficacy across multiple clinically meaningful outcomes in patients with newly diagnosed multiple myeloma. Compared with standard treatment, the addition of isatuximab significantly increased the likelihood of achieving MRD negativity following induction and consolidation (OR 1.99, 95% CI 1.52–2.60), indicating deeper treatment responses. Evidence from individual comparative studies further suggested improved rates of deeper MRD assessment at a sensitivity threshold of 10⁻⁶. These improvements in disease response translated into superior clinical outcomes, with a significant prolongation of progression-free survival (HR 0.70, 95% CI 0.52–0.95). Importantly, treatment intensification with isatuximab did not compromise stem-cell mobilization, as no significant difference was observed in stem-cell collection failure between treatment groups (OR 1.04, 95% CI 0.15–7.32). However, patients receiving isatuximab required plerixafor more frequently during mobilization (OR 1.70, 95% CI 1.08–2.67), suggesting that successful stem-cell collection was maintained with additional mobilization support when necessary. Regarding safety, isatuximab-based regimens were associated with a significantly higher incidence of grade ≥3 infections (OR 1.49, 95% CI 1.12–1.99). Grade ≥3 neutropenia was also more frequent in the comparative study reporting this outcome (OR 2.34, 95% CI 1.37–4.00). In contrast, no statistically significant differences were observed between treatment groups for grade ≥3 anemia (OR 1.34, 95% CI 0.30–6.10), thrombocytopenia (OR 0.82, 95% CI 0.34–1.96), serious adverse events (OR 1.12, 95% CI 0.65–1.95), or treatment discontinuation due to adverse events (OR 1.22, 95% CI 0.51–2.91). Sensitivity analyses demonstrated that the increased risk of grade ≥3 infections remained stable after sequential exclusion of individual studies, supporting the robustness of the pooled estimate. Overall, these findings indicate that the addition of isatuximab improves the depth of response and disease control while maintaining the feasibility of autologous stem-cell transplantation, with a manageable safety profile. Conclusion Isatuximab-based therapy improves the depth of response and prolongs progression-free survival in patients with newly diagnosed multiple myeloma while preserving successful stem-cell mobilization. Although associated with a higher incidence of grade ≥3 infections and neutropenia, the overall safety profile remains manageable, supporting isatuximab-based regimens as an effective frontline treatment option.
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223135175