Drug products: Daratumumab, Darzalex, DARZALEX
ATC code: L01FC01
No differences between men and women have been described for daratumumab in treatment of multiple myeloma.
Multiple myeloma is more common in men (incidence in the US: 7.7/100 000 men and 4.9/100 000 women, respectively) and two-fold more common in blacks than in whites in the US . A retrospective data analysis,patients with multiple myelomas who underwent autologous stem cell transplantation (ASCT) (110 men, 81 women) found no differences between men and women in baseline characteristics or five-year overall survival rate .A population-based study in Medicare beneficiaries (1089 men, 1330 women) in the US found male sex to be a risk factor for death together with older age, more co-morbidities, anemia, and hypercalcemia . This is in concordance with an analysis of the EUROCARE database which includes European adults (15-99 years of age, in all 35 086) diagnosed with multiple myeloma between 1995 and 1999. Women were found to have a higher survival rate compared to men, particularly in age groups over the age of 55 years . In this study, age at diagnosis was the main determinant of women’s good outcome. In elderly women, however, the advantage was negligible, suggesting sex hormone patterns to have a role in the prognosis .
Pharmacokinetics and dosing
Patient’s sex has been shown to have no clinically meaningful effect on pharmacokinetics of daratumumab (in monotherapy or as combination therapy) provided a body weight-based regimen was used [5-7].
In a randomized controlled trial in patients with newly diagnosed multiple myeloma (327 men, 379 women) a beneficial effect of adding daratumumab to bortezomib, melphalan, and prednisone was found in both men and women .An exploratory analysis of data from two randomized studies in patients with relapsed/refractory multiple myeloma (GEN501 and NMY2002, in all 82 men, 69 women) found no difference between men and women in overall response rate .
An exploratory analysis of data from two randomized studies in patients with relapsed/refractory multiple myeloma (GEN501 and NMY2002, in all 82 men, 69 women) found no difference between men and women in overall grade 3 or higher (serious) adverse events or infection of any grade .
Reproductive health issues
As daratumumab is transferred across the placenta and may theoretically cause myeloid- or lymphoid-cell depletion it is recommended that women of reproductive potential should use effective contraception during treatment and for 3 months after cessation of daratumumab treatment [2, 9]. Regarding teratogenic aspects please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2019-02-03
- Dimopoulos MA, Terpos E, Niesvizky R, Palumbo A. Clinical characteristics of patients with relapsed multiple myeloma. Cancer Treat Rev. 2015;41(10):827-35. PubMed
- Posch D, Rabitsch W, Wohlfarth P, Leiner M, Porpaczy E, Drach J et al. Gender-Specific Aspects in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation: A Single-Center Experience. Oncology. 2017;93(5):295-301. PubMed
- Yusuf AA, Natwick T, Werther W, Felici D, Mahue M, Bridges KR et al. A retrospective analysis to examine factors associated with mortality in Medicare beneficiaries newly diagnosed with multiple myeloma. Curr Med Res Opin. 2016;32(12):1989-1996. PubMed
- Micheli A, Ciampichini R, Oberaigner W, Ciccolallo L, de Vries E, Izarzugaza I et al. The advantage of women in cancer survival: an analysis of EUROCARE-4 data. Eur J Cancer. 2009;45(6):1017-27. PubMed
- DARZALEX (daratumumab) DailyMed,. DailyMed [www]. US National Library of Medicine. [updated 2019-10-05, cited 2019-02-03]. länk
- Darzalex (daratumumab). Summary of Product Characteristics. European Medicines Agency (EMA) [updated 2019-01-14, cited 2019-02-03].
- Yan X, Clemens PL, Puchalski T, Lonial S, Lokhorst H, Voorhees PM et al. Influence of Disease and Patient Characteristics on Daratumumab Exposure and Clinical Outcomes in Relapsed or Refractory Multiple Myeloma. Clin Pharmacokinet. 2018;57(4):529-538. PubMed
- Mateos MV, Dimopoulos MA, Cavo M, Suzuki K, Jakubowiak A, Knop S et al. Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma. N Engl J Med. 2018;378(6):518-528. PubMed
- Cejalvo MJ, Ribas P, de la Rubia J. The safety of daratumumab for the treatment of multiple myeloma. Expert Opin Drug Saf. 2017;16(6):753-760. PubMed
- Concise (INSIKT). Kalmar: eHälsomyndigheten. 2018 [cited 2019-03-14.] länk
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson