Carfilzomib (4) – Kyprolis®

• Clinical trials
  • CANDOR is a multicentre, open-label, randomised controlled trial comparing carfilzomib in combination with daratumumab and dexamethasone with carfilzomib in combination with dexamethasone.

Adults with multiple myeloma who have received at least one prior course of treatment

• An additional benefit is not proven for carfilzomib in combination with daratumumab and dexamethasone for the treatment of adults with multiple myeloma who have received at least one prior course of treatment.
• mortality
  • For the endpoint of overall survival, there is no statistically significant difference between carfilzomib in combination with daratumumab and dexamethasone and carfilzomib in combination with dexamethasone.
  • No additional benefit is identified for the endpoint of overall survival.
• Morbidity – Progression-free survival (PFS)
  • PFS is statistically significantly prolonged with carfilzomib in combination with daratumumab and dexamethasone compared with carfilzomib in combination with dexamethasone.
  • The results for the progression-free survival endpoint are not taken into account in this assessment.
• Morbidity – Symptoms
  • Based on these analyses, no statistically significant difference between the study arms was observed for any of the endpoints. With regard to symptoms, therefore, there are neither positive nor negative effects of carfilzomib in combination with daratumumab and dexamethasone.
• Morbidity – Health status (EQ-5D Visual Analogue Scale)
  • For the response criteria of ≥ 10 and ≥ 15 points, respectively, an effect in favour of carfilzomib in combination with daratumumab and dexamethasone is observed.
  • In this regard, uncertainties regarding the result for the response criterion of ≥ 10 points must be taken into account, given the wide limits of the 95% confidence interval for the effect estimator.
• Conclusion regarding symptoms and health status
  • Taking the results as a whole and against this background, no relevant difference is observed for symptoms or health status overall.
• quality of life
  • For the endpoint ‘social functioning’, there is a statistically significant effect in favour of carfilzomib in combination with daratumumab and dexamethasone.
  • Taking the results as a whole and against this background, no relevant difference was found for health-related quality of life overall.
• Side effects – Adverse events (AEs)
  • No statistically significant difference was observed between the study arms for serious adverse events.
  • No statistically significant difference was observed between the study arms for severe adverse events with a CTCAE grade of ≥ 3.
• Side effects – discontinuation due to AEs
  • Based on these analyses, no statistically significant difference was observed between the study arms for the endpoint ‘withdrawal due to AEs’ (with regard to withdrawal from at least one component).
• Side effects – Specific AEs
  • Carfilzomib in combination with daratumumab and dexamethasone showed a statistically significant disadvantage compared with carfilzomib in combination with dexamethasone with regard to the specific AE diarrhoea (PT) and the specific severe AE (CTCAE grade ≥ 3) thrombocytopenia (PT).
  • For the specific severe AEs (CTCAE grade ≥ 3) ‘renal and urinary tract disorders’ (SOC), there is a statistically significant advantage for carfilzomib in combination with daratumumab and dexamethasone.
  • The interpretability of the available data on the cardiotoxicity occurring with carfilzomib in combination with daratumumab and dexamethasone is limited.
• Overall assessment
  • Overall, the G-BA concludes that additional benefit from carfilzomib in combination with daratumumab and dexamethasone is not proven compared with carfilzomib in combination with dexamethasone.

Courtesy translation only, please refer to the German original.