The background is quite simple – a few years ago we established lenalidomide and low dose dexamethasone as a standard of care for newly diagnosed transplant ineligible patients with myeloma. This was achieved in the context of the study called FIRST which was part of the ASH 2013 plenary session in fact. So lenalidomide and low dose dexamethasone is a true standard of care approved and established in many, many countries.
Then we tried to build on lenalidomide and dexamethasone and one of the most attractive drugs a few years ago was daratumumab. We decided to do a large phase III study having lenalidomide dexamethasone versus daratumumab lenalidomide dexamethasone in elderly and newly diagnosed patients with myeloma. So in fact that’s very simple in terms of design, that’s very straightforward, I would say.
The study was very attractive so the study enrolled a little bit more than 700 patients in 14 countries – US, Canada, many European countries, Israel and Australia. The study enrolled patients between 2015 and 2017 and at this meeting we report the first analysis of the study which is called the MAIA study.
The primary endpoint is PFS, as usual, as you know this is the usual primary endpoint in myeloma and myeloma studies. The study met its primary endpoint of PFS. The control arm did very well, the control arm had a median PFS of approximately 32 months which was somewhat longer as compared to what we had in the FIRST study in the past, we had only, I would say, 26 months. But the study met its primary endpoint, the hazard ratio is 0.56 so the median PFS has not been reached for daratumumab lenalidomide and dexamethasone and is expected to be at least 50 months, I would say. So this is a great achievement in terms of PFS.
Of course the survival is not mature. If you look at response, complete response rate, VGPR, overall response, we achieved great results as well. 93% of patients achieved response so almost everybody got response. 48% of patients achieved complete response and 79% of patients achieved at least a very good partial response. At the present time we have 24% of patients MRD negative at 10-5 but in fact we had a very rigorous assessment of MRD so we assessed MRD only in patients in CR. So what we have is an under-estimation of MRD negativity, I would say, and this will increase over time so we may expect getting 30% or more MRD negative patients at the end.
Looking at safety the study looks good. In fact, the safety profile is very, very concordant with what we had noted in the past in other daratumumab studies, especially in combination with either lenalidomide or bortezomib. So, as you know, we have daratumumab lenalidomide dexamethasone in the relapsed setting and we have daratumumab in combination with bortezomib melphalan and prednisone in the front line setting. Basically when you look at safety it is totally as expected. We got a little bit more neutropenia with DRD, very few thrombocytopenias. Looking at non-hematologic adverse events nothing very different except maybe the fact that we had a little bit more pneumonia in the daratumumab arm. This was also observed last year when the daratumumab VMP study was reported. It’s not concerning, it’s a small increase but we may have to work on this. If you look at infusion reactions, that’s approximately 40% of patients but only 3% of patients at grade 3 or more so that’s very minimal and, again, this is as expected, I would say.
This is a lenalidomide study so, as you know, in the past we got some issues with second primary malignancies in some lenalidomide studies so we looked at SPM. When looking at invasive SPM in general, having solid tumours and hematologic SPM, it’s only 3-4% of patients so it’s very reassuring. The median follow-up is not huge but there is no signal. If you look at hematologic SPM that’s 0.5% of patients in each arm so that’s very minimal so there is no SPM discussion at this median follow-up.
So the study looks great and this will, for sure, establish this daratumumab lenalidomide dexamethasone regimen as a new standard of care for the elderly patients with newly diagnosed myeloma.