Belantamab-Mafodotin (1) – Blenrep®

• Clinical trials
  • The DREAMM-2 trial is an ongoing, multicentre study 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 (PI) and an immunomodulatory drug (IMiD), and in whom treatment with an anti-CD38 antibody has failed.
  • The benefit assessment relates solely to a single treatment cohort (N = 97) from the DREAMM-2 study, in which belantamab-mafodotin was administered at the FI-compliant dose of 2.5 mg/kg body weight; appropriate controls are lacking.

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

• Hint for a non-quantifiable additional benefit, as the scientific data do not permit quantification.
• The certainty of the evidence is assessed as a hint because only a single-arm, uncontrolled clinical study is available and a comparative assessment is not possible.
• mortality
  • Overall survival is defined as the time from randomisation to death from any cause.
  • At the data cut-off for the 13-month update on 31 January 2020, 48 (49 %) of the 97 study patients treated with belantamab mafordotin had died. The median survival was 13.7 months.
  • As no comparable data are available, no conclusion can be drawn from these results regarding the extent of the additional benefit.
• morbidity
  • The EORTC QLQ-C30 and QLQ-MY20 were administered in the DREAMM-2 trial every 6 weeks during the treatment period and at the end of treatment.
  • The response rates (data cut-off date: 20 September 2019) for the ITT population fell from 77% at baseline to below 70% for all post-baseline visits.
  • Due to the low response rates, the results of the EORTC questionnaires are not used for the benefit assessment.
  • Consequently, no conclusions regarding the extent of the additional benefit in terms of morbidity can be drawn from the results of the DREAMM-2 study.
• quality of life
  • To assess quality of life, the DREAMM-2 study utilised the functional scales and the global scale for general health status/quality of life from the EORTC QLQ-C30, as well as the functional scales from the QLQ-MY20 and the NEI VFQ-25 questionnaire.
  • As with the patient-reported morbidity endpoints, the response rates for the EORTC questionnaires were so low that no valid results could be derived from them.
  • The NEI VFQ-25 was used in the DREAMM-2 study to assess the impact of potential corneal events on function and health-related quality of life. Due to the descriptive nature of the results, the very short follow-up period of 3 weeks and the lack of a control group, no valid conclusions can be drawn regarding the effects of belantamab-mafodotin on quality of life.
  • Consequently, no conclusions regarding the extent of the additional benefit for quality of life can be drawn from the results of the DREAMM-2 study.
• Side effects
  • The results on side effects relate to the 95 patients in the full safety set population. This population comprises all patients who received at least one dose of the study medication.
  • Total adverse events (AEs)
  • Almost every patient experienced an adverse event (93 patients (98 %)).
  • Serious adverse events (SAEs)
  • At least one serious adverse event (SAE) occurred in 40 of the 95 patients (42 %). The most common events were pneumonia and pyrexia, each occurring in 7 % of patients.
  • Severe adverse events (CTCAE grade ≥ 3)
  • At least one severe AE with a CTCAE grade of ≥ 3 occurred in 80 out of 95 patients (84 %). The most common AEs with a severity grade of ≥ 3 were keratopathies; haematological AEs (including Preferred Terms: anaemia, thrombocytopenia, reduced platelet count, neutropenia, reduced neutrophil count, reduced lymphocyte count) and pneumonia.
  • Therapy discontinuation due to adverse events
  • 9% of patients discontinued treatment due to adverse events.
  • AE of particular interest
  • In the DREAMM-2 study, AEs including infusion-related reactions, thrombocytopenia, neutropenia and corneal events were defined as AEs of particular interest. Infusion-related events occurred in 21% of patients. Thrombocytopenia was observed in 38% of patients. 15% of patients suffered from neutropenia. Corneal events were assessed using both the CTCAE and a classification scale developed by GSK. According to the GSK scale, 72% of treated patients exhibited corneal events, with almost half of these patients also showing symptoms of blurred vision and dry eyes. Almost 50% of all patients had corneal events graded as Grade 3 or 4 on the GSK scale. According to the CTCAE classification, keratopathy was documented in 71% of patients. 31% of these patients had severe keratopathy. Blurred vision and dry eyes, as defined by the CTCAE, were observed in 25% and 15% of treated patients respectively, although the proportion of patients with severe events was minor. No serious corneal events, as defined by the CTCAE, occurred.
  • As the results of the DREAMM-2 study on side effects are based on uncontrolled data, no comparative conclusions can be drawn.
• Overall assessment
  • For the benefit assessment of belantamab-mafodotin in 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-CD38antibody, and who have shown disease progression during their most recent treatment, results are available from the uncontrolled clinical study DREAMM-2 regarding overall survival and side effects.
  • Furthermore, data on morbidity and quality of life are available. However, these have such low response rates that no valid conclusions can be drawn from them. The data are classified as not assessable.
  • Notwithstanding this, a comparative assessment of the study results is not possible due to the single-arm design of the DREAMM-2 study.
  • The results submitted during the commenting procedure regarding indirect comparisons, both between belantamab-mafodotin and selinexor + dexamethasone and between belantamab-mafodotin and ‘conventional care’ via the bridging comparator selinexor + dexamethasone cannot be used to derive any additional benefit, as it remains unclear to what extent the patient populations included in the studies are comparable, and it cannot be ruled out that relevant adjustment and matching factors have not been taken into account, leading to bias in the results.
  • Consequently, it is not possible to carry out a quantitative assessment of the extent of the effect or to quantify the additional benefit on the basis of the data provided.

Courtesy translation only, please refer to the German original.