Daratumumab

(Darzalex®)

Darzalex®

Drug updated on 12/11/2024

Dosage FormInjection (intravenous; 100 mg/5 mL, 400 mg/20 mL)
Drug ClassCD38-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

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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% 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 TitleYearSource
Darzalex (daratumumab) Prescribing Information.2024Janssen Biotech, Inc., Titusville, NJ

Systematic Reviews / Meta-Analyses

Document TitleYearSource
Efficacy of daratumumab on multiple myeloma patients with renal insufficiency: a systematic review and meta-analysis2024Hematology (Amsterdam, Netherlands)
Impact of Anti-CD38 Monoclonal Antibody Therapy on CD34+ Hematopoietic Stem Cell Mobilization, Collection, and Engraftment in Multiple Myeloma Patients-A Systematic Review2024Pharmaceuticals (Basel, Switzerland)
Daratumumab and antineoplastic therapy versus antineoplastic therapy only for adults with newly diagnosed multiple myeloma ineligible for transplant2024The Cochrane Database of Systematic Reviews
Daratumumab-based immunotherapy vs. lenalidomide, bortezomib and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: a systemic review2024Frontiers in Oncology
Efficacy and safety of anti-CD38 monoclonal antibodies in patients with relapsed/refractory multiple myeloma: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials2023Frontiers in Oncology
Daratumumab for autoimmune diseases: a systematic review2023RMD Open
Comparative efficacy of novel-drugs combined therapeutic regimens on relapsed/refractory multiple myeloma: a network meta-analysis2023Hematology (Amsterdam, Netherlands)
Lenalidomide-based triplet regimens in first relapsed multiple myeloma patients: real-world evidence from a propensity score matched analysis2023Haematologica
Daratumumab-based therapies in transplant-ineligible patients with untreated multiple myeloma and hepatic dysfunction: A systematic review of subgroup analyses2023Journal of Oncology Pharmacy Practice
Cumulative Incidence and Relative Risk of Infection in Patients With Multiple Myeloma Treated With Anti-CD38 Monoclonal Antibody-Based Regimens: A Systematic Review and Meta-analysis2022Open Forum Infectious Diseases
Efficacy of maintenance treatment in patients with multiple myeloma: a systematic review and network meta-analysis2022Hematology (Amsterdam, Netherlands)
Network meta-analysis of randomized trials in multiple myeloma: Efficacy and safety in frontline therapy for patients not eligible for transplant2022Hematological Oncology
Treatment Regimens for Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma: A Systematic Literature Review and Network Meta-analysis2022Advances in Therapy
Early versus late response to daratumumab-based triplet therapies in patients with multiple myeloma: a pooled analysis of trials POLLUX, CASTOR and MAIA2022Leukemia & Lymphoma
A Systematic Review of Cost-Effectiveness Analyses of Novel Agents in the Treatment of Multiple Myeloma2021Cancers
Addition of daratumumab to multiple myeloma backbone regimens significantly improves clinical outcomes: a systematic review and meta-analysis of randomised controlled trials2021Scientific Reports
Efficacy and safety of daratumumab in the treatment of multiple myeloma: a systematic review and meta-analysis2021The Journal of International Medical Research
Daratumumab provides a survival benefit in relapsed and refractory Multiple Myeloma, independent of baseline clinical characteristics: A meta-analysis2021Pharmacology Research & Perspectives
A Systematic Review and Network Meta-analysis of Randomized Data on Efficacy of Novel Therapy Combinations in Patients with Lenalidomide-refractory Multiple Myeloma2021Clinical Lymphoma, Myeloma & Leukemia
Daratumumab-based induction therapy for multiple myeloma: A systematic review and meta-analysis2021Critical Reviews in Oncology/Hematology
The role of novel agents for consolidation after autologous transplantation in newly diagnosed multiple myeloma: a systematic review2021Annals of Hematology
Evaluation of Daratumumab for the Treatment of Multiple Myeloma in Patients With High-risk Cytogenetic Factors: A Systematic Review and Meta-analysis2020JAMA Oncology
Risk of thromboembolism in patients with multiple myeloma treated with daratumumab: a systemic review and meta-analysis2020International Journal of Hematology
Efficacy and safety of frontline regimens for older transplant-ineligible patients with multiple myeloma: A systematic review and meta-analysis2020Journal of Geriatric Oncology
Monoclonal antibodies in relapsed/refractory myeloma: updated evidence from clinical trials, real-life studies, and meta-analyses2020Expert Review of Hematology
Relative efficacy of treatment options in transplant-ineligible newly diagnosed multiple myeloma: results from a systematic literature review and network meta-analysis2020Leukemia & Lymphoma
Upfront treatment for newly diagnosed transplant-ineligible multiple myeloma patients: A systematic review and network meta-analysis of 14,533 patients over 29 randomized clinical trials2019Critical Reviews in Oncology/Hematology
Daratumumab added to standard of care in patients with newly diagnosed multiple myeloma: A network meta-analysis2019European Journal of Haematology

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