Daratumumab (9) – Darzalex®

• Clinical trials
  • The MAIA trial compares daratumumab in combination with lenalidomide and dexamethasone against the dual combination of lenalidomide and dexamethasone.

Adults with newly diagnosed multiple myeloma who are not suitable for an autologous stem cell transplant

• There is a hint of considerable additional benefit for daratumumab in combination with lenalidomide and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are not suitable for autologous stem cell transplantation.
• On balance, the G-BA concludes that daratumumab in combination with lenalidomide and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are not suitable for autologous stem cell transplantation offers a considerable additional benefit compared with lenalidomide in combination with dexamethasone.
• The uncertainties mentioned mean that, overall, a hint is derived.
• mortality
  • In the MAIA study, overall survival is defined as the time from randomisation to death, regardless of the underlying cause of death.
  • For the endpoint of overall survival, a statistically significant difference was observed in favour of daratumumab in combination with lenalidomide and dexamethasone.
  • This prolongation of survival time with treatment using daratumumab in combination with lenalidomide and dexamethasone, compared with treatment using lenalidomide in combination with dexamethasone, is regarded as a significant improvement.
• Morbidity – Progression-free survival
  • Progression-free survival (PFS) is the primary endpoint of the MAIA study. It is defined as the time from randomisation to the occurrence of disease progression according to IMWG criteria or death.
  • With daratumumab in combination with lenalidomide and dexamethasone, PFS was statistically significantly prolonged compared with lenalidomide in combination with dexamethasone.
  • The PFS endpoint is a composite endpoint comprising endpoints from the ‘mortality’ and ‘morbidity’ categories.
• Morbidity – Symptoms
  • In the MAIA study, disease symptoms were assessed using the symptom scales of the cancer-specific EORTC QLQ-C30 questionnaire.
  • Statistically significant advantages of daratumumab in combination with lenalidomide and dexamethasone were observed for the endpoints ‘pain’ and ‘dyspnoea’.
  • For all other endpoints, no statistically significant difference was observed between the study arms.
  • Overall, therefore, there is an advantage of daratumumab in combination with lenalidomide and dexamethasone in terms of symptoms.
• Morbidity – Health status (EQ-5D Visual Analogue Scale)
  • General health status is assessed in the MAIA study using the EQ-5D visual analogue scale (VAS).
  • No statistically significant difference was observed between the study arms for any of the three response thresholds.
  • With regard to health status, therefore, there are neither positive nor negative effects of daratumumab in combination with lenalidomide and dexamethasone.
• Health-related quality of life
  • Health-related quality of life is assessed in the MAIA study using the functional scales of the cancer-specific EORTC QLQ-C30 questionnaire.
  • Statistically significant advantages of daratumumab in combination with lenalidomide and dexamethasone were observed for the endpoints ‘physical functioning’ and ‘social functioning’.
  • For all other endpoints, no statistically significant difference was observed between the study arms.
  • Overall, therefore, there is an advantage of daratumumab in combination with lenalidomide and dexamethasone in terms of health-related quality of life.
• Side effects – Adverse events (AE)
  • All endpoints in the AE category are monitored for up to 30 days after the last dose of the study medication, until the withdrawal of informed consent, or until the start of subsequent myeloma treatment, whichever occurs first.
• Side effects – Serious adverse events (SAEs)
  • No statistically significant difference was observed between the study arms with regard to serious adverse events.
• Side effects – Severe AEs (CTCAE grade ≥ 3)
  • For severe adverse events with a CTCAE grade of ≥ 3, there is a significant disadvantage compared to daratumumab in combination with lenalidomide and dexamethasone.
• Side effects – Discontinuation due to AEs
  • No statistically significant difference was observed between the study arms for the endpoint of discontinuation due to AEs.
• Overall assessment
  • For the endpoint of overall survival, the available results show a statistically significant prolongation of survival with treatment using daratumumab in combination with lenalidomide and dexamethasone compared with treatment using lenalidomide in combination with dexamethasone, which is assessed as a marked improvement.
  • With regard to symptoms (assessed using the EORTC QLQ-C30), advantages were observed for treatment with daratumumab in combination with lenalidomide and dexamethasone for the endpoints of pain and dyspnoea.
  • With regard to health status (assessed using the EQ-5D VAS), there was no statistically significant difference between the study arms.
  • With regard to health-related quality of life (assessed using the EORTC QLQ-C30), there were advantages for daratumumab in combination with lenalidomide and dexamethasone in terms of the endpoints of physical functioning and social functioning.
  • With regard to adverse events, the daratumumab triple combination has a disadvantage in terms of the incidence of severe adverse events (CTCAE grade ≥ 3).
  • Overall, a significant improvement in terms of prolonged survival, as well as advantages in symptoms and quality of life, is offset by a disadvantage in the incidence of severe adverse events (CTCAE grade ≥ 3).
  • This disadvantage is considered moderate.

Courtesy translation only, please refer to the German original.