Good morning everybody. It’s my pleasure to be presenting this first analysis of the study called MAIA. MAIA is lenalidomide/dexamethasone versus daratumumab in combination with lenalidomide/dexamethasone in newly diagnosed elderly patients with myeloma. So this is the rationale of the study. We know that lenalidomide and dexamethasone has been established as a standard of care for the elderly patients a few years ago. The study was called the FIRST study and was presented at ASH plenary in 2013. In the FIRST study the median PFS for lenalidomide and dexamethasone was 26 months; after the FIRST study VRd was investigated and is considered to be another standard of care based on several studies including one US study done in the elderly. In this FOX study the median PFS for patients over the age of 65 is 34 months. Daratumumab in combination with lenalidomide and dexamethasone has also been used and approved in the relapsed setting. The study was called the POLLUX study and the median PFS for DRd in the relapsed setting is quite impressive at 44.5 months.
Finally, as I said before, this phase III MAIA study, which is a very large phase III international study evaluated DRd versus Rd for patients who are transplant ineligible. We report here the first pre-specified analysis of the study. This is the study design. The study enrolled 737 patients, so eligibility criteria are the usual in this disease – transplant ineligible patients; ECOG zero to two; creatinine clearance over 30. The control arm, as said before, is lenalidomide and dexamethasone as it has been approved. Daratumumab in the DRd arm is delivered at the dose of 16mg/kg weekly for the first two cycles, every two weeks between cycles 3 and 6 and then every four weeks. Both regimens are delivered until progressive myeloma and the primary endpoint is progression free survival with all other usual secondary endpoints.
This is the study population. The median age is 73 years. Importantly, and as you can appreciate, 44% of patients have an age over 75. So this is likely something extremely important; in the vast majority of registration studies in myeloma we have approximately one-third of patients with an age over 75 so we have in this study 10% more. Otherwise ECOG two was 17% of patients, ISS3 was about 30% of patients and 14% of patients had high risk cytogenetics. DRd and Rd treatment arms were well balanced regarding characteristics.
This is the primary endpoint of PFS. The median follow-up is 28 months. The study met its primary endpoint – the median PFS for the control arm is 31.5 months which is significantly longer as we noted in the FIRST study in the past. The hazard ratio is 0.56 and, as you can appreciate the 30 months PFS is 71% for DRd versus 56% for the Rd control arm. This is the response rate and also shown here is MRD negativity. We got significantly higher response rates, including CR rate, VGPR rate and MRD negative rate with DRd. In the DRd arm 93% of patients achieved at least partial response; 48% of patients achieved complete response and 79% of patients achieved at least a very good partial response. 24% of patient achieved MRD negativity in a very conservative way to assess MRD negativity and there was a great difference between Rd and DRd for MRD achievement.
Safety was very manageable. Basically we have to say that the safety profile is very consistent with findings coming from other studies having daratumumab combined with standards of care such as the POLLUX study and the ALCYONE study which was the combination of daratumumab with VMP. Looking at hematologic adverse events we got a little bit more neutropenia, grade 3/4 – 35% in the control arm versus 50%. Looking at non-hematologic toxicities there is only one finding which is different – we got a little bit more pneumonia; the incidence of grade 3/4 pneumonia was 8% in the control arm versus 14% in the DRd arm. The rate of infusion reactions was as expected at 41% but very few patients had grade 3/4 infusion reactions. Incidence of SPM was very low – 3% and 4% in DRd and Rd respectively – and very, very few patients had a hematologic SPM, so 0.5% in each arm. Finally treatment emergent adverse events with outcome of death was 7% for DRd and 6% for Rd.
These are the conclusions: DRd significantly reduced the risk of progression or death by 44% in patients with transplant ineligible, newly diagnosed myeloma. DRd induced significantly deeper responses, including a threefold higher incidence of MRD negativity. No new safety signals were observed using DRd in newly diagnosed myeloma. So we believe that this study has established DRd as a new standard of care for patients who are ineligible for autologous stem cell transplantation. Thank you.