Belantamab-Mafodotin (2) – Blenrep®

• Clinical trials
  • For the benefit assessment of the active ingredient belantamab-mafodotin, the pharmaceutical manufacturer cites the ongoing, randomised, open-label, multicentre Phase IIIDREAMM-3 trial – which is still ongoing – comparing belantamab-mafodotin with pomalidomide in combination with dexamethasone, as well as the pivotal, uncontrolled Phase II DREAMM-2 trial.
  • The DREAMM-3 study is an open-label, randomised, multicentre Phase III study comparing belantamab-mafodotin with pomalidomide in combination with dexamethasone.
  • The DREAMM-2 trial is a multicentre Phase II trial designed to evaluate the efficacy and safety of two doses of belantamab-mafodotin in patients with multiple myeloma who have previously received three or more lines of treatment, are refractory to a proteasome inhibitor and an immunomodulator, and in whom treatment with an anti-CD38 antibody has failed.

Adults with multiple myeloma who have already received at least four lines of treatment and whose disease is refractory to at least one proteasome inhibitor, one immunomodulator and one monoclonal anti-CD38 antibody, and who showed disease progression during their most recent treatment

• The G-BA classifies the extent of the additional benefit of belantamab-Mafodotin, from a purely legal perspective pursuant to Section 35a(1), sentence 11, first clause, of the German Social Code, Book V (SGB V), as non-quantifiable, based on the criteria set out in Section 5(7) of the AM-NutzenV, taking into account the severity of the disease and the therapeutic objective in treating the disease.
• An additional benefit exists in accordance with Section 35a(1), sentence 11, first clause, of SGB V, but is non-quantifiable because the scientific evidence does not permit this.
• On balance, the G-BA determines, from a purely legal perspective in accordance with Section 35a(1), sentence 11, first clause, of SGB V, that there is a non-quantifiable additional benefit for belantamab-mafodotin.
• mortality
  • Overall survival is defined in the DREAMM-2 and DREAMM-3 studies as the time from randomisation to death from any cause.
  • There is no statistically significant difference in overall survival between the study arms as of the primary data cut-off for the DREAMM-3 study on 12 September 2022.
  • In the evaluable patient population of the DREAMM-3 trial, 16 patients (55%) died in the belantamab-mafodotin arm and 4 patients (27%) in the pomalidomide/dexamethasone arm.
  • The median survival time in the intervention arm is 9.5 months (95% CI: [5.1; n.a.]), whilst it has not yet been reached in the control arm.
  • When evaluating the overall survival results from the DREAMM-3 trial, the minor precision of the estimate (wide confidence interval) and the low event rate due to the still short follow-up period at this primary data cut-off must be taken into account.
  • Furthermore, despite a stratified analysis of overall survival by ISS stage and line of treatment in the DREAMM-3 trial, uncertainties remain regarding the homogeneity of the treatment groups due to the small 5L+ patient population.
• Morbidity – Progression-free survival (PFS)
  • Progression-free survival is the primary endpoint of the DREAMM-3 study.
  • In the DREAMM-2 and DREAMM-3 studies, PFS is defined as the time from randomisation to the earliest date of documented disease progression or death from any cause, whichever occurs first.
  • There is no statistically significant difference in PFS between the study arms in the 5L+ patient population of the DREAMM-3 study.
  • The morbidity component ‘disease progression’ is assessed according to IMWG criteria and is therefore not symptom-based, but rather determined using laboratory parameters, imaging and haematological procedures.
• Morbidity – Symptoms (EORTC QLQ-C30 / EORTC QLQ-MY20/IL52)
  • Disease symptoms were assessed in the DREAMM-2 and DREAMM-3 studies using the symptom scales of the cancer-specific questionnaire EORTC QLQ-C30 and the myeloma-specific supplementary module EORTC QLQ-MY20.
  • Only the relevant analyses of the symptom scales of the EORTC QLQ-C30 and the EORTC QLQ-MY20 (only the ‘disease symptoms’ subscale) from the DREAMM-3 study at the Week 4 assessment point are included, as the respective response rates exceeded 70% at this assessment point.
  • The analyses for week 4 are descriptive and merely provide information on the respective proportion of participants who experienced a deterioration of ≥ 10 points by week 4.
  • Owing to the aforementioned uncertainties regarding the results on symptoms from the EORTC QLQ-C30 and EORTC QLQ-M20/IL52 questionnaires, which were used for the benefit assessment, these are deemed to be unevaluable.
• quality of life
  • Health-related quality of life was assessed in the DREAMM-2 and DREAMM-3 studies 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.
  • Only the relevant data for the functional scales and the global health status scale of the EORTC QLQ-C30 from the DREAMM-3 study at the Week 4 assessment point are included, as the respective response rates for these measures were above 70%.
  • Owing to the aforementioned uncertainties regarding the results of the EORTC QLQ-C30 questionnaire on health-related quality of life used for the benefit assessment, these are deemed to be unassessable.
• Side effects – Total adverse events (AEs)
  • Adverse events (AEs) occurred in almost all patients in both the belantamab mafordotin arms of the DREAMM-2 and DREAMM-3 studies and in the pomalidomide arm of the DREAMM-3 study.
• Overall assessment
  • This assessment constitutes a renewed benefit assessment following the limitation set out in the G-BA’s initial decision of 4 March 2021 regarding belantamab-mafodotin for the treatment of adult patients with multiple myeloma, who have already received at least four prior therapies and whose disease is refractory to at least one proteasome inhibitor, one immunomodulator and one monoclonal anti-CD38 antibody, and who have shown disease progression during their most recent therapy.
  • For the re-assessment of benefits, the final data from the single-arm Phase II DREAMM-2 trial, on which the marketing authorisation was based, and the data from the primary data cut-off of the open-label, randomised DREAMM-3 trial comparing belantamab mafordotin with pomalidomide and dexamethasone are now available.
  • Due to the single-arm study design, the data from the DREAMM-2 study do not allow for a comparative assessment.
  • In the patient population of the DREAMM-3 study relevant for the assessment, there is no statistically significant difference in overall survival between belantamab-mafodotin and pomalidomide/dexamethasone.
  • No evaluable data are available for assessing morbidity (disease symptoms, cancer symptoms, health status) and quality of life.
  • With regard to the results on side effects, the DREAMM-3 study did not reveal any differences between the treatment arms that are relevant for the benefit assessment. In detail, with regard to adverse events of particular interest, there is a disadvantage for Belantamab-Mafodotin compared with pomalidomide and dexamethasone in terms of corneal events.
  • Overall, the G-BA has determined, from a purely legal perspective pursuant to Section 35a(1), sentence 11, first clause of SGB V, that belantamab-mafodotin offers a non-quantifiable additional benefit.

Courtesy translation only, please refer to the German original.