Preparat: Kyprolis, KYPROLIS
ATC kod: L01XG02
Subgruppsanalys av en stor randomiserad klinisk studie har visat god effekt hos både kvinnor och män. En post-hoc analys av karfilzomibstudier fann att kvinnligt kön var en prediktor för bättre överlevnad. Eftersom djurstudier indikerar att karfilzomib är teratogent rekommenderas god antikonception för både män och kvinnor under behandlingen och under 3-6 månader efter.
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 .
Patient’s sex has not been reported to have any clinically meaningful effects on pharmacokinetics of carfilzomib .
In the pivotal study in patients with relapsed multiple myeloma (449 men, 345 women), predefined subgroup analysis showed that progression free survival was better in both men and women treated with carfilzomib in combination with lenalidomide and dexamethasone (26.3 months) compared to those treated with lenalidomide and dexamethasone alone (17.6 months) .In a post-hoc analysis of overall survival on carfilzomib treatment in three clinical studies (in all 268 men, 184 women), female sex was one factor predicting better survival .
Differences between men and women in cardiotoxicity has been analyzed in a small study (29 men, 21 women). Global longitudinal strain was decreased in patients treated with carfilzomib but no difference between men and women was found in multivariable regression analysis .
Concomitant use of oral contraceptives (OC) is not recommended due to the risk of thrombosis but also as the risk of lower effect of the OC can’t be ignored . Carfilzomib should be avoided during pregnancy as animal studies suggest teratogenic effects. Thus, it is recommended that women treated with carfilzomib (and/or their partner) use effective anticonception during and for six months after the treatment. For men, effective anticonception is recommended during and for three months after the treatment . Regarding teratogenic aspects please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
Läkemedel innehållande karfilzomib (ATC-kod L01XX45) används huvudsakligen på sjukhus och därför saknas könsspecifika användningsdata .
Faktagranskat av: Mia von Euler
Godkänt av: Karin Schenck-Gustafsson