Elotuzumab (2) – Empliciti®

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

Adult 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 progression during their most recent therapy

• Overall, the G-BA concludes that, for E-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 progression during their most recent treatment, there is a considerable additional benefit compared with Pd.
• On balance, there is a hint of considerable additional benefit for E-Pd compared with Pd in the treatment of patients with relapsed and refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor, and who have shown progression on their most recent treatment.
• Taking the uncertainties described into account, there is an overall hint of an additional benefit of E-Pd.
• mortality
  • For the endpoint of overall survival, there is a statistically significant difference in favour of E-Pd compared with Pd (hazard ratio (HR): 0.54 [95% confidence interval (CI): 0.30; 0.96]; p-value = 0.034).
  • The median survival time had not yet been reached in the group of patients receiving E-Pd at the second data cut-off on 29 November 2018.
  • This is interpreted as a considerable prolongation of overall survival with elotuzumab in combination with pomalidomide and dexamethasone.
  • With regard to overall survival, the ELOQUENT-3 trial demonstrates an advantage of E-Pd over Pd, whose extent is classified as considerable.
• Morbidity – Progression-free survival (PFS)
  • PFS was the primary endpoint of the ELOQUENT-3 trial and was defined as the time from randomisation to tumour progression or death from any cause.
  • A statistically significant difference in favour of elotuzumab was observed for PFS (hazard ratio (HR): 0.499 [95% confidence interval (CI): 0.325; 0.765]; p-value = 0.0011).
  • Patients in the E-Pd group had a median progression-free survival benefit of 5.55 months compared with patients in the Pd group.
  • The PFS endpoint is a composite endpoint comprising endpoints from the categories of mortality and morbidity.
  • Taking the above aspects into account, there are differing views within the G-BA regarding the clinical relevance of the PFS endpoint.
• quality of life
  • The health-related quality of life endpoint 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.
  • Consequently, no suitable data are available for the assessment of the quality of life endpoint category.
• Side effects – Total adverse events (AEs)
  • Adverse events occurred at least once in almost all patients, regardless of the treatment arm.
  • The results for the endpoint ‘adverse events’ (AEs) are presented only as supplementary information, as the operationalisation of side effects also includes events that are not relevant to patients.
• Overall assessment / Conclusion
  • For the assessment of the additional benefit compared with E-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 progression during their most recent treatment, the ELOQUENT-3 trial provides results on mortality (overall survival), morbidity and side effects.
  • With regard to overall survival, the ELOQUENT-3 trial demonstrates an advantage of E-Pd over Pd, whose extent is classified as considerable.
  • In the morbidity category, there was no statistically significant difference between the treatment arms for the endpoints of health status and symptoms.
  • No suitable data on health-related quality of life are available from the ELOQUENT-3 study.
  • In the overall analysis of the results on side effects, statistically significant differences were observed in severe AEs (CTCAE Grade 3 to 4) for patients who had received 2 or 3 prior lines of treatment, and, more specifically, for the specific adverse events neutropenia and anaemia.
  • In the overall assessment of all endpoints, a minor advantage of E-Pd over Pd is observed in the side effects category.
  • In its overall assessment, the G-BA concludes that for E-Pd in the treatment of patients with relapsed and refractory multiple myeloma who have already received at least two prior lines of therapy, 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.
• Overall assessment / Conclusion
  • For the assessment of the additional benefit of E-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 progression on their most recent treatment, results from the ELOQUENT-3 trial are available on mortality (overall survival), morbidity and side effects.
  • With regard to overall survival, the ELOQUENT-3 trial demonstrates an advantage of E-Pd over Pd, whose extent is classified as considerable.
  • In the morbidity category, there was no statistically significant difference between the treatment arms for the endpoints of health status and symptoms.
  • No suitable data on health-related quality of life are available from the ELOQUENT-3 study.
  • In the overall analysis of the results on side effects, statistically significant differences were observed in severe AEs (CTCAE Grade 3 to 4) for patients who had received 2 or 3 prior lines of treatment, and, more specifically, for the specific adverse events neutropenia and anaemia.
  • In the overall assessment of all endpoints, a minor advantage of E-Pd over Pd is observed in the side effects category.
  • In its overall assessment, the G-BA concludes that for E-Pd in the treatment of patients with relapsed and refractory multiple myeloma who have already received at least two prior lines of therapy, including lenalidomide and a proteasome inhibitor, and who have shown disease progression during their most recent treatment, there is a considerable additional benefit compared with Pd.

Courtesy translation only, please refer to the German original.