Ixazomib (2) – Ninlaro®

• Clinical trials
  • This study is a randomised, controlled, double-blind, multicentre Phase III trial in which ixazomib in combination with lenalidomide and dexamethasone (ixazomib/LenDex) was compared with lenalidomide and dexamethasone (LenDex).

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

• Evidence of a non-quantifiable additional benefit, as the scientific data do not permit quantification
• A hint can be derived with regard to the certainty of the findings.
• Consequently, the extent of the additional benefit is classified as non-quantifiable, as the scientific evidence does not permit quantification.
• mortality
  • In the C16010 study, overall survival is defined as the time from randomisation to death from any cause.
  • For the endpoint of overall survival, there is no statistically significant difference between the treatment groups when considering the study’s overall population.
  • There is an effect modification by the characteristic ‘prior treatment with bortezomib’ for overall survival. Accordingly, for patients without prior bortezomib therapy, there is a statistically significant effect in favour of ixazomib / LenDex.
  • In contrast, for patients who had previously received bortezomib, no significant difference was observed between the treatment groups.
  • For these reasons, the observed effect modification by the characteristic ‘previous bortezomib therapy’ is not considered sufficient to derive separate conclusions regarding additional benefit in the overall assessment.
• Morbidity – Progression-free survival
  • Progression-free survival (PFS) was the primary endpoint of the C16010 study. PFS was defined as the time from randomisation to the first documented disease progression (as defined by the International Myeloma Working Group, IMWG) or the patient’s death, regardless of the cause of death – whichever occurred first.
  • There was no statistically significant difference between the treatment arms.
• Morbidity – Pain (BPI-SF)
  • Self-reported pain was assessed using the Brief Pain Inventory-Short Form (BPI-SF) and was recorded until the occurrence of disease progression, death or withdrawal from the study.
  • No statistically significant differences were observed between the treatment groups, either in the four items of the ‘Pain Intensity’ domain or in the score across the seven items of the ‘Pain Interference’ domain (9A–9G).
• Morbidity – Symptoms (EORTC QLQ-C30 / EORTC QLQ-MY20)
  • In the C16010 trial, disease symptoms were assessed using the cancer-specific EORTC QLQ-C30 questionnaire and the myeloma-specific supplementary module EORTC QLQ-MY20 until the onset of disease progression.
  • In the analysis of ‘time to first deterioration’ by ≥ 10 points, a statistically significant difference in favour of ixazomib/LenDex over Len/Dex was observed only for the ‘loss of appetite’ domain.
  • Based on this alone, no advantage can be inferred from the overall assessment of the results regarding symptoms.
  • There are therefore no relevant differences between the treatment arms with regard to symptoms.
• Morbidity – General health status (EQ-5D VAS)
  • In the C16010 study, health status is assessed using the EQ-5D visual analogue scale (VAS) from the onset of the disease until death or the end of the study.
  • No statistically significant difference between the treatment arms could be identified for this analysis.
• Health-related quality of life
  • Health-related quality of life was assessed in the C16010 study using the functional scales and the global health status scale of the cancer-specific EORTC QLQ-C30 and the myeloma-specific supplementary module EORTC QLQ-MY20, up to the onset of disease progression.
  • In the analyses of ‘time to first deterioration’ by ≥ 10 points, a statistically significant difference was observed for the ‘Global Health Status / Overall Quality of Life’ domain, a statistically significant disadvantage was observed compared with Len/Dex for ixazomib/LenDex, and for the ‘Future Prospects’ domain, a statistically significant advantage was observed compared with Len/Dex for ixazomib/LenDex.
  • When the results are considered as a whole, no relevant difference is observed in health-related quality of life overall.
• Side effects – Adverse events (AEs), total
  • In the C16010 study, almost all randomised patients experienced at least one adverse event.
• Side effects – Serious adverse events (SAEs), severe AEs (CTCAE grade ≥ 3), discontinuation due to AEs
  • For the endpoints serious adverse events (SAEs), severe AEs (CTCAE grade ≥ 3) and discontinuation due to AEs, there is no statistically significant difference between the treatment arms in any case.
  • With regard to severe AEs, a detailed analysis shows an advantage for ixazomib/LenDex over LenDex in the case of renal and urinary tract disorders (SOC), and a disadvantage in the case of skin and subcutaneous tissue disorders (SOC).
• Conclusion on side effects
  • An overall review of the results on side effects reveals no differences between the treatment arms that are relevant to the benefit assessment.
• Overall assessment / Conclusion
  • For the endpoint of overall survival, there is no statistically significant difference between the treatment groups.
  • For the endpoints in the morbidity category, an overall review of the results reveals no major differences between the treatment groups with regard to symptoms (assessed using the EORTC QLQ-C30 and EORTC QLQ-MY20), general health status (assessed using the EQ-5D VAS) and pain (BPI-SF), there are no major differences between treatment with ixazomib in combination with lenalidomide and dexamethasone and treatment with lenalidomide in combination with dexamethasone.
  • With regard to health-related quality of life (assessed using the EORTC QLQ-C30 and EORTC QLQ-MY20), the overall analysis of the results also reveals no major differences.
  • An overall review of the results on side effects reveals no differences between the treatment arms that are relevant to the benefit assessment.
  • Consequently, the extent of the additional benefit is classified as non-quantifiable, as the scientific evidence does not permit quantification.

Courtesy translation only, please refer to the German original.