Isatuximab (3) – Sarclisa®

• Clinical trials
  • In the ongoing IMROZ trial, isatuximab in combination with bortezomib + lenalidomide + dexamethasone (Isa-VRd regimen) is being compared with bortezomib + lenalidomide + dexamethasone (VRd regimen).

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

• Hint of a minor additional benefit
• Taking into account the uncertainties mentioned, there is, on the whole, a hint that supports the observed additional benefit.
• mortality
  • In the IMROZ 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 arms.
• Morbidity – Progression-free survival (PFS)
  • In the IMROZ study, progression-free survival is defined as the time from randomisation to the date of the first documented disease progression (as assessed by the Independent Review Committee [IRC]) or the date of death from any cause, whichever occurs first.
  • For the PFS endpoint, there is a statistically significant advantage for isatuximab + bortezomib + lenalidomide + dexamethasone.
  • Taking the above aspects into account, there are differing views within the G-BA regarding the clinical relevance of the PFS endpoint for patients.
• Morbidity – EORTC-QLQ C30
  • In the IMROZ study, disease symptoms were assessed using the cancer-specific EORTC-QLQ C30 questionnaire.
  • For the symptom of dyspnoea, the study shows a statistically significant advantage in favour of isatuximab + bortezomib + lenalidomide + dexamethasone.
  • Furthermore, a statistically significant advantage in favour of isatuximab + bortezomib + lenalidomide + dexamethasone was observed for the symptoms of nausea, vomiting and loss of appetite.
  • For the remaining symptoms – fatigue, pain, insomnia, constipation and diarrhoea – no statistically significant difference was observed between the treatment arms in any case.
• Morbidity – EORCT QLQ-MY20
  • For the endpoints of disease symptoms and side effects, assessed using the EORCT QLQ-MY20, there was no statistically significant difference between the treatment arms in either case.
• Morbidity – Health status according to EQ-5D VAS
  • In this study, health status is assessed using the visual analogue scale (VAS) of the EQ-5D.
  • No statistically significant difference in health status was observed between the treatment arms.
• Quality of life – EORTC-QLQ C30
  • Health-related quality of life is assessed in the IMROZ study using the functional scales of the EORTC-QLQ C30 and the supplementary module EORTC QLQ-MY20 (future prospects, body image).
  • For role functioning, there is a statistically significant advantage in favour of isatuximab + bortezomib + lenalidomide + dexamethasone.
  • For the remaining functional scales assessed using the EORTC-QLQ C30 (overall health status, physical functioning, emotional functioning, cognitive functioning, social functioning), there is no statistically significant difference between the treatment arms in any case.
• Quality of life – EORTC QLQ-MY20
  • For outlook on the future, assessed using the EORTC QLQ-MY20, there is a statistically significant advantage in favour of isatuximab + bortezomib + lenalidomide + dexamethasone.
  • There was no statistically significant difference between the treatment arms in terms of body image.
• Side effects – Serious adverse events (SAEs) and severe adverse events (AEs)
  • For the endpoints SUEs and severe AEs, there were no statistically significant differences between the treatment arms in the study.
• Side effects – Discontinuation due to adverse events
  • With regard to the analyses submitted by the pharmaceutical manufacturer during the commenting procedure, which resolve the uncertainties in the analyses presented in the dossier, there is no statistically significant difference between the treatment arms.
• Conclusion on side effects
  • Overall, there are no statistically significant differences between the treatment arms in the endpoint category of side effects for SAE, severe AE, and discontinuations due to AE.
  • In detail, isatuximab + bortezomib + lenalidomide + dexamethasone shows advantages for certain specific adverse events (metabolic and nutritional disorders, and disorders of the respiratory tract, thoracic cavity and mediastinum).
  • Given that no statistically significant differences were observed in the overall rates of AEs, SUE and severe AEs, these advantages are considered insufficient to lead to a conclusion other than that there is no relevant difference for the ‘side effects’ endpoint category as a whole.
• Overall assessment
  • Data are available from the IMROZ study to assess the additional benefit of isatuximab in combination with bortezomib, lenalidomide and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are not suitable for autologous stem cell transplantation, the IMROZ study provides results on mortality, morbidity, quality of life and side effects compared with the combination therapy of bortezomib, lenalidomide and dexamethasone.
  • No significant difference in overall survival was observed between the study arms.
  • With regard to symptoms, assessed using the EORTC QLQ-C30 and EORTC QLQ-MY20, an overall benefit was observed for isatuximab plus bortezomib plus lenalidomide plus dexamethasone, based on improvements, particularly in the endpoints of dyspnoea, nausea and vomiting, an overall advantage was observed for isatuximab + bortezomib + lenalidomide + dexamethasone.
  • In terms of health-related quality of life, assessed using the EORTC QLQ-C30 and EORTC QLQ-MY20, improvements were observed in role functioning and future outlook, which is why an overall advantage can be observed for isatuximab + bortezomib + lenalidomide + dexamethasone.
  • With regard to the endpoint category of side effects, there were no statistically significant differences between the treatment arms in the overall rates of severe side effects (SAEs), severe unanticipated events (SUEs) or treatment discontinuations due to side effects.
  • Overall, the G-BA concludes that isatuximab in combination with bortezomib, lenalidomide and dexamethasone provide a minor additional benefit for the treatment of adult patients with newly diagnosed multiple myeloma who are not suitable for autologous stem cell transplantation.

Courtesy translation only, please refer to the German original.