Drug updated on 12/11/2024
Dosage Form | Injection (intravenous; 100 mg/5 mL, 400 mg/20 mL) |
Drug Class | CD38-directed cytolytic antibodies |
Ongoing and Completed Studies | ClinicalTrials.gov |
Indication
- Indicated in combination with lenalidomide and dexamethasone for the treatment of adults newly diagnosed adult patients with multiple myeloma who are ineligible for autologous stem cell transplant and in adult patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
- Indicated in combination with bortezomib, melphalan and prednisone for the treatment of adult patients newly diagnosed with multiple myeloma who are ineligible for autologous stem cell transplant
- Indicated in combination with bortezomib, thalidomide and dexamethasone for the treatment of adult patients newly diagnosed with multiple myeloma who are ineligible for autologous stem cell transplant
- Indicated in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy
- Indicated in combination with carfilzomib and dexamethasone in adult patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
- Indicated in combination with pomalidomide and dexamethasone in adult patients with multiple myeloma who have received at least two prior lines of therapy including lenalidomide and a proteasome inhibitor
- Indicated as a monotherapy for adult patients with multiple myeloma who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.
Latest News
Summary
- 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% confidence interval (CI), 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 European Organization for Research and Treatment of Cancer (EORTC) 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 NDMM, 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.
Product Monograph / Prescribing Information
Document Title | Year | Source |
---|---|---|
Darzalex (daratumumab) Prescribing Information. | 2024 | Janssen Biotech, Inc., Titusville, NJ |
Systematic Reviews / Meta-Analyses
Clinical Practice Guidelines
Document Title | Year | Source |
---|---|---|
Multiple myeloma, version 2.2024, NCCN clinical practice guidelines in oncology | 2023 | Journal of the NCCN |
Clinical practice guideline multiple myeloma | 2022 | Myeloma Australia |
Practical considerations for the daratumumab management in Portuguese routine clinical practice: recommendations from an expert panel of hematologists | 2021 | Frontiers in Oncology |
Multiple myeloma: EHA-ESMO clinical practice guidelines for diagnosis, treatment and follow-up | 2021 | Annals of Oncology |
Treatment of multiple myeloma: ASCO and CCO joint clinical practice guideline | 2019 | Journal of Clinical Oncology |