We have exciting new data in myeloma during this European Haematology Association congress in Amsterdam. We focused first on newly-diagnosed myeloma patients. We will have the opportunity to see new data coming from daratumumab, the monoclonal antibody targeting CD38, that will be added to a standard of care we use in newly-diagnosed myeloma patients transplant-eligible, VTd – bortezomib, thalidomide and dexamethasone. This combination is going to be evaluated in a phase III randomised study. The phase III randomised study basically will compare the VTd plus daratumumab as part of the induction, follow it by transplant and consolidation with VTd plus daratumumab, versus VTd transplant and VTd without daratumumab.
The results are positive at the primary endpoint, a stringent complete response, but I think that the take-home message is that the benefit in progression free survival with a hazard ratio of 0.43 indicating that maybe we are in front of a new standard of care for newly-diagnosed myeloma patients transplant eligible. In this setting, I think that the Italian Myeloma Group will present an update also of an interesting trial in which the second-generation proteasome inhibitor carfilzomib is being evaluated in combination with lenalidomide and dexamethasone, followed or not by autologous stem cell transplantation. This is the FORTE study and Francesca Gay will have compared KRD transplant/KRD versus KRD without autologous stem cell transplantation. She will give, I think, important messages because although the follow-up is short and we are not going to see any data about progression-free survival, I think that it’s interesting to see how maybe the transplant will have a significant role in patients with advanced stage of the disease or high-risk cytogenetic abnormalities, whilst maybe in the near future we can potentially put a question mark for the transplant in the up front setting in patients at standard risk in patients with ISS-1. I think that this is going to be also interesting.
Another option that I would like to highlight is the curative option for asymptomatic myeloma patients. In line with the combination that Francesca Gay will present, KRD, the Spanish Myeloma Group has evaluated KRD transplant, KRD consolidation and maintenance in a series of 90 high-risk smouldering myeloma patients. The results are encouraging with minimal residual disease negative rate after autologous stem cell transplantation over 50% with excellent data in terms of PFS and overall survival. The follow-up is short, and of course we have to wait to have a longer follow-up, but I would say that the strategy seems to be very encouraging, especially because we are dealing with asymptomatic myeloma patients.
In the relapsed setting I think that we are going to have also new combinations. Pomalidomide and dexamethasone is standard of care for relapsed and refractory myeloma patients in third line and beyond, and during this European congress Professor Richardson from the US will present the results of the Phase III ICARIA study – pom/dex versus pom/dex plus isatuximab, another CD38 monoclonal antibody. The primary endpoint is PFS and if we decided to add this monoclonal antibody to pomalidomide and dexamethasone the PFS is going to be significantly longer and the median PFS is of approximately one year. So, again, we are going to be maybe in front of a new standard of care for this population.
Finally, I would like also to mention the role of daratumumab, the CD38 monoclonal antibody, but used in a new formulation of subcutaneous administration. The COLUMBA study is a Phase III, non-inferiority randomised trial in which we will have the opportunity to demonstrate that daratumumab subQ is not inferior to daratumumab IV, but the main findings are that daratumumab subQ is administered at flat dose, 1800mg, and in just five minutes. In addition the safety profile in terms of reactions to the infusion is significantly lower in comparison with the daratumumab IV and I think that one important finding is that patients reported more satisfaction when they received daratumumab subQ versus daratumumab IV. So I think that this presentation is relevant for the physicians, it’s relevant for the hospitals, but especially is relevant for the patient care.
And finally, let me just comment while new drugs, new cell modes, iberdomide is a new immunomodulatory drug that will be evaluated in relapsed and refractory myeloma patients, late advanced stage of the disease, but again, promising efficacy and safety results.