Isatuximab (2) – Sarclisa®

• Clinical trials
  • The benefit assessment of the active ingredient isatuximab is based on the ongoing, pivotal IKEMA trial. This is an open-label, randomised, controlled, multicentre Phase III trial in which the triple combination of isatuximab, carfilzomib and dexamethasone (Isa-Kd) is compared with the dual combination of carfilzomib and dexamethasone (Kd).

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

• An additional benefit is not proven for the treatment of multiple myeloma in adults who have received at least one prior course of treatment.
• mortality
  • overall survival
  • No statistically significant difference was observed between the treatment arms for the endpoint of overall mortality. The median survival time has not yet been reached in either study arm.
  • No additional benefit for Isa-Kd is therefore identified for the endpoint of overall survival.
• morbidity
  • Progression-free survival
  • Progression-free survival (PFS) is the primary endpoint of the IKEMA study. PFS was defined as the time from randomisation to the date of the first documented disease progression or the date of death from any cause, whichever occurred first.
  • There is a statistically significant advantage for isatuximab in combination with carfilzomib and dexamethasone (Isa-Kd) compared with carfilzomib in combination with dexamethasone (Kd).
  • Taking the above aspects into account, there are differing views within the G-BA regarding the clinical relevance of the PFS endpoint to patients. The overall conclusion regarding additional benefit remains unaffected by this, as even if the present PFS result were taken into account in the overall assessment, the overall conclusion regarding the extent of the additional benefit would remain unchanged.
  • Symptoms
  • With regard to the progressive worsening of disease symptoms, no statistically significant differences were observed between the treatment arms.
  • health status
  • No statistically significant difference was observed between the treatment arms for any of the response criteria.
  • Overall, in the morbidity endpoint category, there are no differences between Isa-Kd and Kd that are relevant to the benefit assessment.
• quality of life
  • No statistically significant difference was observed between the treatment arms for any of the response criteria.
  • There are therefore no advantages or disadvantages of Isa-Kd compared with Kd in the quality of life endpoint category.
• Side effects
  • In accordance with the IKEMA study protocol, laboratory values were only reported as an adverse event (AE) if they led to discontinuation of treatment, resulted in a dose modification, or constituted a serious adverse event (SAE) or an adverse event of special interest (AESI). This potentially results in incomplete recording, particularly of severe AEs.
  • Serious SAEs (SAEs) and severe AEs (CTCAE grade ≥ 3)
  • There were no statistically significant differences between the treatment arms for the endpoints SAE and severe AEs (CTCAE grade ≥ 3).
  • Therapy discontinuations due to AEs
  • Based on the analysis of the time to discontinuation of at least one active ingredient, there is no statistically significant difference between the treatment arms.
  • Specific AEs
  • For the AEs ‘Infusion-related reactions’ (PT) and ‘Skin and subcutaneous tissue disorders’ (SOC), statistically significant differences were observed between the treatment arms, with a disadvantage for Isa-Kd compared with Kd. For the severe AE (CTCAE grade ≥ 3) thrombocytopenia (PT), however, there is a statistically significant advantage in favour of Isa-Kd compared with Kd.
  • Overall, the results on side effects show no differences between the treatment arms that are relevant for the benefit assessment. In detail, for the specific adverse events, infusion-related reactions (PT) and disorders of the skin and subcutaneous tissue (SOC) show disadvantages, whilst for thrombocytopenia (PT) there is an advantage for Isa-Kd compared with Kd.
• Overall assessment
  • There is no statistically significant difference between the treatment arms in terms of overall survival.
  • In the endpoint categories of morbidity and health-related quality of life (assessed using the EORTC QLQ-C30, EORTC QLQ-MY20 and EQ-5D VAS), there are also no statistically significant differences between Isa-Kd and Kd.
  • An overall review of the results on side effects reveals no differences between the treatment arms that are relevant to the benefit assessment. In detail, however, there are disadvantages for Isa-Kd compared with Kd in terms of the specific adverse events ‘infusion-related reactions’ (PT) and ‘skin and subcutaneous tissue disorders’ (SOC), as well as an advantage for Isa-Kd over Kd in terms of ‘thrombocytopenia’ (PT).
  • In its overall assessment, the G-BA concludes that, for the treatment of adults with multiple myeloma who have received at least one prior course of therapy, additional benefit is not proven for isatuximab in combination with carfilzomib and dexamethasone compared with carfilzomib and dexamethasone.

Courtesy translation only, please refer to the German original.