Transplant Ineligible Multiple Myeloma: Updates to the MAIA Study - Episode 3
Updated results from the MAIA trial, which tested the addition of daratumumab to lenalidomide-dexamethasone therapy in patients with transplant-ineligible newly diagnosed multiple myeloma.
Peter Voorhees, MD: The MAIA trial was a randomized phase 3 trial that looked at lenalidomide and dexamethasone with or without the CD38 monoclonal antibody daratumumab in newly diagnosed patients with transplant-ineligible multiple myeloma. Patients were assigned 1:1 to the 2 arms, and patients were treated until disease progression or the emergence of unacceptable adverse effects. The primary end point of the study was progression-free survival [PFS]. Other key secondary end points include depth of response, including MRD [minimal residual disease] negativity, overall survival, progression-free survival, as well as safety.
As far as baseline characteristics, the 2 arms of the trial were well matched. It’s important to note that close to 45% of the patients in the trial were 75 years of age and older, so this is representative of an older patient population. Interestingly, 30% of patients in both arms had ISS [International Staging System] stage III disease. High ISS stage is well represented in this trial. As far as high-risk cytogenetics are concerned, that was seen in about 15% of patients in both arms of the trial. The addition of daratumumab to the lenalidomide-dexamethasone backbone improved overall response rate. With long follow-up, overall response rate in the triplet arm was 93% in contrast with 82% for those on the doublet arm; that was statistically significant. When you look at CR [complete response] rates, that was 51% in the triplet arm vs 30% for those in the lenalidomide-dexamethasone arm, so that’s very clear improvement in complete response or better. When you look at MRD negativity at 10-5 level of sensitivity, there were much higher rates in the triplet arm vs the doublet arm. When you look at sustained MRD negativity over 12 months, there were much higher rates in the triplet arm vs the doublet arm.
Dr Thierry Facon of the University of Lille [in France] updated the MAIA results at the European Hematology Association Congress [EHA] earlier this year. Remarkably, with long follow-up, the progression-free survival for daratumumab, lenalidomide, and dexamethasone at 60 months, or 5 years, was 52.5%. We still haven’t hit median progression-free survival 5 years out. That’s in contrast with a 5-year progression-free survival rate of 28.7% for those assigned to lenalidomide-dexamethasone. The median progression-free survival was 34.4 months, so that’s a dramatic improvement in progression-free survival with the addition of daratumumab. The hazard ratio for PFS was 0.53, so you’re looking at a 47% reduction in the risk of progression or death with the addition of daratumumab to the lenalidomide-dexamethasone backbone. Importantly, overall survival was also updated at EHA. Looking at the 60-month overall survival rate, it was 66.3% in the triplet arm in contrast with 53.1% in the doublet arm, and that was highly statistically significant. The hazard ratio was 0.68, so you’re looking at a 32% reduction in the risk of death of any cause with the addition of daratumumab to the lenalidomide-dexamethasone backbone. What we’re seeing is that the addition of that CD38 antibody improves overall response and depth of response, which translates into progression-free survival and, with long enough follow-up in many instances, overall survival.
Transcript edited for clarity.