Thank you Dr Hagenbeek. Good morning. I would like to give you some data regarding this phase III study comparing VTd versus VTd plus daratumumab in the setting of autologous stem cell transplantation front line treatment of young patients. This study is an academic study sponsored by the French Cooperative Group, IFM, together with the Dutch Cooperative Group, HOVON. As you know, stem cell transplantation in Europe and in many countries around the globe is standard of care as part of front line treatment for young patients. VTd, the combination of bortezomib, thalidomide and dexamethasone, prior to and also after stem cell transplantation is also a triplet that is widely used, standard of care in Europe. But right now we don’t know what is the impact of daratumumab, a monoclonal antibody targeting CD38, in the setting of stem cell transplantation. So this study is the first one looking at the impact of daratumumab for young patients treated aggressively with autologous stem cell transplantation.
So this is the study design, a very simple design. VTd before and after stem cell transplantation plus or minus daratumumab in patients less than 66 years of age with symptomatic multiple myeloma. The study has two parts. Part 1 is to look with the primary endpoint of stringent CR and the response rate after consolidation. Then the second part is a maintenance phase with daratumumab versus no daratumumab maintenance. Here during the meeting we are showing the results, the final results, of the first part of the study.
So in terms of response we are showing that daratumumab is highly increasing the response rate. The stringent CR rate is highly improved but also the MRD negativity rate and we have a very strict definition of stringent CR. You see that the addition of daratumumab is also increasing the complete response rate. This quality of response, this depth of response, translates into a better progression free survival. You see here the 18 month PFS – 93% in the daratumumab arm of the study. Those results are the best ever reported in the setting of stem cell transplantation.
Of note, we have enrolled more than 1,000 patients into the study in less than two years in 111 sites. So you can see that the huge involvement in the Netherlands, in Belgium and in France to try to answer this very important question.
The hazard ratio is less than 0.5 and we have here a very important benefit for the patients. The median follow-up is 18 months so the overall survival data are immature but nevertheless we are already seeing a trend for a better overall survival in the daratumumab arm of the study and the two year overall survival is 97% in the daratumumab arm. For patients with symptomatic myeloma those results are really unprecedented results in my opinion.
So, in conclusion, we are showing that the addition of daratumumab on top of VTd in the setting of stem cell transplantation is increasing the response rate, the MRD negativity rate, translating into a progression free survival benefit.
In terms of toxicity no additional toxicity when using daratumumab in the setting of stem cell transplantation. For the stem cell harvest we looked also carefully at haematopoietic reconstitution after stem cell transplantation and there was really no issue with the use of daratumumab. So this study is a pivotal study for the approval of daratumumab, not only in the US but also in Europe and in many other countries in the setting of stem cell transplantation. So currently we are waiting for the responses of EMA, of FDA, but VTd-dara is already approved and used based on our study in Brazil, for example. While I don’t have the paper published in The New England Journal of Medicine unfortunately but it was published on the day of the presentation at ASCO in The Lancet, that’s not so bad in fact. Thank you for your kind attention.
Prof Anton Hagenbeek
Thank you very much for this great study that you’ve just presented. Questions to the speaker? Do you consider this now to be the standard of care from now when we go home or is it still too early to promote that?
Prof Philippe Moreau
No, I think that if approved and if reimbursed, because in Europe we have many issues regarding the cost and the reimbursement of drugs and combinations, for sure we will consider dara-VTd as standard of care. VTd is standard of care in many, many countries in Europe and given those results I think that yes, definitely.
Prof Anton Hagenbeek