Bortezomib and dexamethasone demonstrate efficacy benefit in key subgroups vs daratumumab, bortezomib, and dexamethasone in RRMM
Dr Maria-Victoria Mateos - University Hospital Salamanca, Salamanca, Spain
I will present the results of the DREAMM-7 clinical trial. It is a phase III randomised trial conducted in relapsed refractory myeloma patients after at least one prior line of therapy in which belantamab mafodotin in combination with bortezomib and dexamethasone has been compared with daratumumab in combination with bortezomib and dexamethasone.
To contextualise this study, the vast majority of newly diagnosed myeloma patients are being treated right now with proteasome inhibitors, immunomodulatory drugs and anti-CD38 monoclonal antibodies. This means that at first relapse this population is going to be triple class exposed and we need a novel mechanism of action. Belantamab mafodotin is a BCMA antibody combined with monomethyl auristatin F so this is a new compound and has been combined with bortezomib and dexamethasone in this study.
494 relapsed/refractory myeloma patients were included and the schedule of treatment included eight induction cycles with bela/Vd or dara/Vd in each arm followed by maintenance therapy with either belantamab mafodotin or daratumumab as continuous therapy. Baseline characteristics of the patients were well balanced and the primary endpoint was progression free survival.
The trial met its primary endpoint: bela/Vd resulted in a median progression free survival of 36.6 months whilst dara/Vd resulted in a median PFS of 13.4 months. This means that the prolongation of the PFS for bela/Vd over dara/Vd was 23 months and the hazard ratio was 0.4. The superiority was sustained across different pre-specified subgroups of patients including those with a disease refractory to lenalidomide or patients with high risk cytogenetic abnormalities. The response rate was also superior for bela/Vd as well as complete remission rate or better – it was double for bela/Vd, 37%, versus 14% for dara/Vd. Also the minimal residual disease negativity rate was significantly superior.
Overall survival showed a clear and strong trend to be also superior for bela/Vd versus dara/Vd. In terms of safety profile, I would say that it is consistent with the known safety profile for each compound. Occular events are maybe the most relevant Belamaf related toxicity but I have to say that throughout the evaluation of the best corrected visual acuity, 34% of the patients experienced a worsening on their visual acuity to what we can call blurred vision, and only 2% of the patients to a clear worsening of the visual acuity to what we can call impaired vision. This ocular toxicity was manageable with dose modification and dose delays and resolved in basically all patients. Only 9% of the patients had to discontinue because of ocular events.
Quality of life was comparable between both arms and I would say that, to conclude, based on these robust efficacy data with an acceptable safety profile, it makes sense to consider that belantamab in combination with Vd can be a potential new standard of care for relapsed refractory myeloma after at least one prior line of therapy.
Thank you very much.
