Daratumumab

Additional information

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 [1]. 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 [2].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 [3]. 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 [4]. 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 [4].

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].

Effects

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 [8].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 [7].

Adverse effects

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 [7].

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).