Journal Article

Efficacy and safety of anti-CD38 monoclonal antibodies-based therapy versus standard therapy in newly diagnosed multiple myeloma patients: a systematic review and meta-analysis

Ullah, Mehran, Osama, Muhammad, Afridi, Abdullah, Rehman, Wajeeh Ur, Khan, Safeena, Ullah, Ubaid, Khan, Muhammad Haris, Hussain, Amna, Tahir, Ammara

2025

Overview

Background: Anti-CD38 monoclonal antibodies (mAbs) have significantly changed the multiple myeloma treatment landscape. This meta-analysis compared the efficacy and safety of anti-CD38 mAb-based therapy versus standard therapy in newly diagnosed multiple myeloma (NDMM) patients. Methods: We performed a comprehensive literature search on PubMed, the Cochrane Database, and ClinicalTrials.gov. The primary outcomes were progression-free survival (PFS) and minimal residual disease (MRD) status. Dichotomous outcomes were pooled using risk ratio (RR) along with the 95% confidence interval (CI) in RevMan 5.4. Subgroup analysis and meta-regression analysis were performed. The RoB 2.0 tool was used to assess the risk of bias. Results: Our meta-analysis included 11 randomized controlled trials. There were 5270 patients; 3040 TEs and 2230 TIEs. Anti-CD38 mAbs significantly improved MRD negativity (RR 1.94, 95% CI: 1.59–2.37; p < 0.00001) and PFS (RR 0.51, 95% CI: 0.45–0.58; p < 0.00001). Subgroup analyses revealed better outcomes for both the TE (MRD: RR 1.52, 95% CI: 1.37–1.68; PFS: RR 0.43, 95% CI: 0.34–0.54) and TIE (MRD: RR 3.49, 95% CI: 2.65–4.61; PFS: RR 0.55, 95% CI: 0.47–0.64) populations. Meta-regression revealed that Eastern Cooperative Oncology Group (ECOG) score 0 significantly influenced MRD status (β = −0.015, p < 0.05), whereas ECOG scores 1 and 2 lacked statistical significance. Subgroup analysis revealed that PFS was significantly different between standard (RR 0.47) and high (RR 0.81) cytogenetic risk groups. Conclusion: In NDMM patients, anti-CD38 mAb-based therapy significantly improved MRD status, and PFS compared with standard therapy alone, in both TE and TIE patients, suggesting a favorable benefit–risk profile. Plain language summary How effective and safe are new anti-CD38 antibody treatments compared to standard therapy for patients with newly diagnosed multiple myeloma? A review and analysis Why was this study conducted? Anti-CD38 monoclonal antibodies (mAbs) have improved the course of treatment for multiple myeloma (MM), a type of blood cancer. These medications may provide better results since they target particular MM cells. In patients recently diagnosed with multiple myeloma (NDMM), this study compared the safety and efficacy of these novel treatments with standard therapy. What did the researchers do? Data from 11 clinical trials with 5,270 NDMM patients were examined by the researchers. They examined two primary outcomes: minimal residual disease (MRD), which looks at the remaining cancer in the body after treatment, and progression-free survival (PFS), which measures how long patients live without the disease getting worse. Patients were separated into two categories: those who qualified for a stem cell transplant (TE) and those who did not (TIE). What did the researchers find? The results showed that anti-CD38 mAbs significantly improved patient outcomes. More patients achieved MRD negativity (lower cancer levels) and had longer PFS compared to those on standard therapy. For TE patients, anti-CD38 mAbs improved MRD by 52% and PFS by 57%. TIE patients saw even greater benefits, with a 249% increase in MRD negativity and a 45% improvement in PFS. What do these results mean? This study demonstrates that, regardless of a patient’s eligibility for a stem cell transplant, anti-CD38 monoclonal antibodies are useful in the treatment of recently diagnosed multiple myeloma. These results imply that this treatment may slow the course of the disease and lower cancer levels in a large number of patients, demonstrating a positive benefit–risk profile for potential future therapeutic strategies.

• Publisher: SAGE Publications,Sage Publications Ltd,SAGE Publishing
• Subject: Cancer therapies / Medical research / Meta-Analysis / Monoclonal antibodies / Multiple myeloma / Patients / Stem cell transplantation