“We found that this induction induced exceptionally high response and minimal residual disease (MRD) negativity rates,” said first author Aurore Perrot, MD, PhD, an associate professor of hematology at the University of Toulouse in France, in presenting the findings at the annual meeting of the International Myeloma Society (IMS).
“These rates are the highest reported to date regarding MRD negativity,” she said.
The results from a first interim analysis offer encouraging groundwork in the trial that is investigating the tailoring of subsequent therapeutic choices in patients with newly diagnosed MM based on MRD status after six cycles of induction therapy.
In the standard treatment regimen of induction therapy followed by up-front autologous stem cell transplant (ASCT), the use of ever-improving quadruplet regimens is bolstering prognoses, while the role of up-front ASCT continues to be debated, Perrot explained. She noted that no prospective trials have compared up-front transplant vs no transplant following a quadruplet regimen.
In reporting on the initial findings from the induction phase of the phase 3 IFM 2020-02 MIDAS study, Perrot described results among 791 transplant-eligible patients with newly diagnosed MM and a median age of 59 who were enrolled at 72 centers between December 2021 and July 2023.
The patients were treated with six cycles of 28 days of the Isa-KRd regimen, consisting of isatuximab 10 mg/kg (weekly for 4 weeks then biweekly), carfilzomib 20 mg/m2 on day 1 cycle 1, then 56 mg/m2 (days 1, 8, and 15), lenalidomide 25 mg/d (from day 1 to day 21), and dexamethasone at 40 mg/wk.
Overall, MM was classified as International Staging System (ISS) III in 120 patients (15%) and revised-ISS III in 76 (10%) patients.
Of 757 patients undergoing cytogenetics, 8% were considered high risk on the basis of a linear predictor score > 1, while the t(11;14) translocation, a chromosomal abnormality, was present in 26% of patients.
Extramedullary disease was present in five patients, while 53 (7%) had circulating plasma cells.
All 791 patients initiated Isa-KRd induction, and most (766, 97%) had at least one peripheral stem cell mobilization course, with 761 having at least one apheresis. The median number of CD34+ cells collected was 7.106/kg.
The peripheral stem cells collected allowed for potential tandem transplants in 719 patients. In total, 757 patients completed six cycles of Isa-KRd, with an overall response rate of 95%.
In the intent-to-treat (ITT) population, a very good partial response or better was achieved in 92% of patients following induction, with a rate of 99% in the per-protocol [PP] population.
Of 751 patients in the post-induction ITT population, the MRD negativity rates were 63% at the threshold of 10−5 and 47% at the threshold of 10−6, with corresponding rates of 66% and 50%, respectively, in the PP population.
The rates of near-complete response and complete response were 64% and 66% in the ITT population, and 69% and 71% in the PP population.
Of note, no significant differences were observed in prognostic subgroups, with a trend for a higher MRD negative rate among poorer prognostic groups, Perrot said.
However, notable variability was observed in terms of MRD negativity at 10−5 after induction among some cytogenic groups, with an MRD negativity rate as high as 81% among patients with the t(4;14) translocation vs 62% among those without the abnormality (P = .002), while it was only 40% among patients with the t(11;14) translocation vs 64% without (P < .0001).
“This is the first time we have observed this correlation between the MRD negativity and these cytogenetic subgroups,” Perrot noted.
“For the moment, we are not saying that patients with the t(11;14) translocation have a poor prognosis,” she added. “But just that the early assessment of MRD shows the lower negativity rates.”