Elotuzumab (3) – Empliciti®

• Clinical trials
  • ELOQUENT-3 is a multicentre, open-label, randomised, controlled Phase II trial comparing the triple combination of elotuzumab, pomalidomide and dexamethasone (E-Pd) is compared with the dual combination of pomalidomide and dexamethasone (Pd).

Adults with relapsed and refractory multiple myeloma who have received at least two prior lines of treatment, including lenalidomide and a proteasome inhibitor, and who have shown disease progression during their most recent treatment

• Consequently, the G-BA has determined that E-Pd offers considerable additional benefit compared with Pd.
• The certainty of the evidence for the established additional benefit is classified as ‘hint’.
• mortality
  • In the ELOQUENT-3 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 in favour of elotuzumab in combination with pomalidomide and dexamethasone was observed in the study’s overall population.
  • For the overall survival endpoint, treatment with E-Pd resulted in a prolongation of survival time compared with treatment with Pd in the overall population of the ELOQUENT-3 study, which is considered a significant improvement.
• Morbidity – Progression-free survival (PFS)
  • PFS was the primary endpoint of the ELOQUENT-3 study and was defined as the time from randomisation to tumour progression or death from any cause.
  • Whilst PFS data were available for the second data cut-off on 29 November 2018, which formed the basis for the G-BA’s initial assessment of E-Pd, data on PFS were available, no PFS data are available for the final analysis of overall survival based on the data cut-off of 22 February 2021.
• Morbidity – Health status (assessed using the EQ-5D VAS)
  • Health status was assessed using the visual analogue scale (VAS) of the EQ-5D questionnaire.
  • 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 elotuzumab in combination with pomalidomide and dexamethasone.
• Morbidity – Symptoms (assessed using the MDASI-MM questionnaire)
  • The MDASI-MM questionnaire was used in the ELOQUENT-3 trial to assess symptoms.
  • For the endpoints of symptom severity and impairment of daily life due to symptoms, no statistically significant difference was observed between the study arms in either case.
  • Accordingly, there are neither positive nor negative effects of elotuzumab in combination with pomalidomide and dexamethasone with regard to symptoms.
• quality of life
  • The endpoint of health-related quality of life was assessed in the ELOQUENT-3 study using the Symptom Interference Score from the MDASI-MM questionnaire.
  • However, this does not fully cover the dimension of health-related quality of life and was already assigned to the morbidity endpoint category during the initial assessment.
  • Consequently, no suitable data are available for the assessment of the quality of life endpoint category.
• 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 adverse events (CTCAE grade ≥ 3)
  • For severe adverse events with a CTCAE grade of ≥ 3, a statistically significant advantage was observed in favour of E-Pd compared with Pd when considering the overall study population.
  • An effect modification was observed based on the characteristic ‘number of prior lines of treatment’. For patients with 2 or 3 prior lines of treatment, a statistically significant advantage was observed in favour of E-Pd compared with Pd. For patients with 4 or more prior lines of treatment, no statistically significant difference was observed.
• Side effects – discontinuation due to adverse events (AE)
  • No statistically significant difference was observed between the study arms for the endpoint of discontinuation due to AEs.
• Side effects
  • Overall, E-Pd showed an advantage over Pd in terms of side effects relating to the endpoint of severe adverse events (CTCAE grade ≥ 3).
  • No statistically significant differences were observed between the study arms for the endpoints of serious AEs and discontinuation due to AEs.
  • When all endpoints are considered together, an advantage of E-Pd over Pd is observed in the side effects category.
• Overall assessment
  • For the endpoint of overall survival, the available results show a statistically significant prolongation of survival with treatment with E-Pd compared with treatment with Pd, which is assessed as a marked improvement.
  • No statistically significant difference was observed between the treatment arms for symptoms (assessed using the MDASI-MM) and health status (assessed using the EQ-5D VAS).
  • No suitable data on health-related quality of life are available from the ELOQUENT-3 study.
  • With regard to side effects, an advantage of E-Pd over Pd was observed for the endpoint of severe adverse events (CTCAE grade ≥ 3). No difference was observed for the endpoints of serious AEs or treatment discontinuation due to AEs. In the category of side effects, therefore, an overall advantage of E-Pd over Pd can be observed.
  • In its overall assessment, the G-BA concludes that E-Pd offers a considerable additional benefit compared with Pd in the treatment of patients with relapsed and refractory multiple myeloma who have already received at least two prior therapies, including lenalidomide and a proteasome inhibitor, and who have shown disease progression during their most recent treatment, E-Pd offers considerable additional benefit compared with Pd.

Courtesy translation only, please refer to the German original.