Belantamab mafodotin, pomalidomide and dexamethasone shows superior efficacy in RRMM compared to standard of care in 2nd line

Prof Meletios Dimopoulos - University of Athens, Athens, Greece

DREAMM-8 is a prospective randomised trial which included 300 patients who were randomised to receive either belantamab mafodotin, or belamaf, with pomalidomide and dexamethasone, or pomalidomide and dexamethasone with bortezomib. Patients were included if they had received at least one prior line of therapy and up to three prior lines of therapy. Patients were included if they had received lenalidomide, they were also eligible if they had received daratumumab and also they could have received bortezomib or carfilzomib but they should not be resistant or intolerant to proteasome inhibitors.

The dose of belantamab mafodotin at the beginning was 2.5mg/kg every four weeks but after the first course the dose was reduced to 1.9mg/kg. The administration of pomalidomide, bortezomib and dexamethasone was as usual. The primary endpoint of the study was progression free survival; secondary endpoints: complete response rate, MRD negativity, overall survival, progression free survival 2.

The main endpoint of the study was met with a significant improvement of the progression free survival and a hazard ratio of 0.52 meaning that the administration of belamaf with pomalidomide and dexamethasone was associated with a 50% chance to decrease the risk of death or progression. Furthermore, the complete response rate was three times higher in favour of the belamaf combination and the MRD negativity rate, again, was five times higher.

As far as toxicities were concerned, the main toxicity associated with the combination is the well-established ocular toxicity due to belamaf. About one third of the patients developed blurred vision and this was treated by holding the administration of belamaf and administering the drug every 8 weeks or every 12 weeks as needed until there was a recovery of the visual acuity to the baseline. The other toxicities were comparable between the two arms.

Furthermore, overall survival analysis indicates that there is a trend for improved survival in favour of the belamaf combination with a hazard ratio of 0.77.

Taking together all this data indicates that we may have a new standard of care – the combination of belantamab mafodotin with pomalidomide and dexamethasone, which is suited for patients who progress on lenalidomide. This is the majority of the patients with myeloma today receive lenalidomide maintenance and also for patients who have been exposed or resistant to anti-CD38 such as daratumumab.

Thank you.