Summary

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• This summary is based on the review of 28 systematic review(s)/meta-analysis(es). ^[1-28]
• Overall Survival (OS) and Progression-Free Survival (PFS): Daratumumab significantly improved OS in both newly diagnosed multiple myeloma (NDMM) with a hazard ratio (HR) of 0.64 (95% CI (confidence interval), 0.53-0.76) and relapsed/refractory multiple myeloma (RRMM) with an HR of 0.737 (95% CI, 0.657-0.827). Progression-free survival also showed improvement, with NDMM achieving an HR of 0.48 (95% CI, 0.39-0.58) and RRMM an HR of 0.552 (95% CI, 0.461-0.659).
• Response Rates: Daratumumab-containing regimens demonstrated higher overall response rates (Objective Response Rate, ORR) with a risk ratio (RR) of 1.21 (95% CI, 1.15-1.28), including notable increases in complete response (CR) and stringent complete response (sCR) rates.
• Quality of Life: Treatment with daratumumab resulted in slight improvements in quality of life, measured on the EORTC (European Organization for Research and Treatment of Cancer) QLQ-C30 global health status scale (GHS), although specific scores were not provided.
• Comparative Efficacy: Network meta-analyses ranked daratumumab-based regimens, such as DRd and DVMP, higher in efficacy for PFS and OS compared to traditional therapies like lenalidomide/bortezomib/dexamethasone (RVD).
• Adverse Events (AEs): Daratumumab treatment was associated with a higher frequency of serious adverse events (RR 1.18, 95% CI, 1.02-1.37), including elevated rates of hematologic AEs such as thrombocytopenia and neutropenia. Non-hematologic adverse events commonly observed included diarrhea, pyrexia, back pain, arthralgia, fatigue, insomnia, and hypertension.
• Infection Risk: Patients receiving daratumumab had a higher cumulative incidence of both any-grade and severe infections, especially upper respiratory tract infections and pneumonia. However, no increased risk of varicella-zoster virus reactivation was reported.
• Discontinuation Rates: Lower discontinuation rates due to adverse events were observed in daratumumab-based regimens compared to RVD/RVD-lite in transplant-ineligible NDMM patients (16% vs. 7%).
• Daratumumab demonstrated consistent benefits across various multiple myeloma subtypes, including newly diagnosed (NDMM), relapsed/refractory (RRMM), and high-risk patients with specific cytogenetic abnormalities (e.g., t(4;14), t(14;16), del(17p)). Efficacy was comparable between patients with renal insufficiency and those with normal renal function, and it also showed promise in patients with therapy-refractory autoimmune diseases, achieving remission or improvement in 81% of cases.