Sarclisa (isatuximab-irfc) plus Velcade (bortezomib), Revlimid (lenalidomide) and dexamethasone (a regimen known as Isa-VRd), followed by Isa-Rd maintenance, lengthened the time patients lived without their disease worsening compared with VRd alone, followed by Rd maintenance, in patients with newly diagnosed, transplant-ineligible multiple myeloma, according to data from the phase 3 IMROZ trial simultaneously presented at the 2024 ASCO Annual Meeting and published in The New England Journal of Medicine.
At a median follow-up of 59.7 months, patients treated with Isa-VRd (265 patients) followed by Isa-Rd experienced a median progression-free survival (PFS; time patients live before disease worsening) that was not reached (NR) compared with 54.34 months in patients treated with VRd alone. A median PFS that was not reached, meaning that not enough patients experienced disease progression or death for the researchers to calculate an average time to one of those events.
Notably, the 60-month PFS rate was 63.2% in the Isa-VRd group versus 45.2% in the VRd group. This PFS benefit was seen across most subgroups, including some difficult-to-treat populations with negative prognostic factors.
"IMROZ is the first global, phase 3 study of an anti-CD38 monoclonal antibody in combination with VRd in patients with transplant-ineligible myeloma. In this presentation, we [showed] that the IMROZ regimen led to a statistically significant improvement in PFS, deep response rates with statistically significant improvements in complete response [CR] and minimal residual disease [MRD]-negative CR, sustained in MRD negativity, and a safety profile consistent with that of each agent,” lead study author Dr. Thierry Facon, stated in a presentation of the data.
Facon is a professor of hematology in the Department of Hematology at Lille University Hospital in France.
In May 2024, the FDA granted priority review to the supplemental biologics license application seeking the approval of Isa-VRd for the treatment of patients with newly diagnosed, transplant-ineligible multiple myeloma, based on data from IMROZ.
The global, prospective, randomized, open-label study was conducted at 102 sites across 21 countries. Investigators enrolled patients 80 years of age or younger with newly diagnosed multiple myeloma who were not considered eligible for transplant due to advanced age or comorbidities.
Patients were randomly assigned to either the Isa-VRd group and VRd group. Treatment continued until disease progression, unacceptable side effects or patient withdrawal. Notably, patients in the VRd group who experienced disease progression during continuous therapy were permitted to cross over to receive Isa-Rd.
The main goal of the study was PFS, and key secondary end points included CR rate (percentage of patients whose disease disappeared), MRD-negative CR rate (cancer cells could not be detected in blood tests), very good partial response (VGPR; myeloma-related protein decreased by 90% or more) or better rate and overall survival (OS; time from treatment until death of any cause).
Although OS data were immature at data cutoff, an interim OS analysis showed a favorable trend for Isa-VRd. The five-year OS rate was 72.3% and 66.3% for patients treated with Isa-VRd versus VRd, respectively.
The overall response rate (indicating the percentage of patients whose disease responded to treatment) was 91.3% for Isa-VRd and 92.3% for VRd. Notably, the CR or better rate was 74.7% for Isa-VRd and 64.1% for VRd. The VGPR or better rate was 89.1% and 82.9% for Isa-VRd and VRd, respectively.
In the Isa-VRd population, 58.1% of patients were MRD negative compared with 43.6% of those given VRd. The rate of patients who achieved an MRD-negative CR were 55.5% and 40.9%, respectively. MRD negativity was sustained for at least 12 months 46.8% and 24.3% of patients, respectively. The median time to MRD negativity was 14.72 months in the Isa-VRd group versus 32.79 months in the VRd group.
Additionally, as measured by a verified scale used to gather data on functioning and quality of life, overall quality of life remained stable over time in both groups, with no negative impact from adding Sarclisa.
Among all patients who received at least one dose of their assigned regimen, the median treatment duration was 53.2 months for the Isa-VRd group (263 patients) and 31.3 months for the VRd group (181 patients). At data cutoff, 47.2% and 24.3% of patients, respectively, were still on treatment.
Any-grade treatment-emergent side effects occurred in 99.6% of patients in the Isa-VRd group and 98.3% of patients in the VRd group. Moderate to severe (grade 3 or higher) side effects were reported in 91.6% and 84.0% of patients, respectively. The incidence of treatment-related deaths was 11% for Isa-VRd and 5.5% for VRd. Serious side effects occurred in 70.7% and 67.4% of patients, respectively.
Side effects leading to permanently stopping treatment were observed in 22.8% of patients given Isa-VRd and 26.0% of patients administered VRd.
"The exposure-adjusted incidence rates suggest the difference in incidence of grade 5 [side effects] between groups was largely driven by the difference in treatment exposure," Facon said in the presentation.
Any-grade side effects of note included neutropenia (decrease in a type of white blood cells; Isa-VRd, 87.5%; VRd, 80.1%); infections (91.3%; 96.7%), including pneumonia (30.0%; 19.3%) and upper raspatory infections (34.2%; 33.7%); diarrhea (54.8%; 48.6%); peripheral sensory neuropathy (54.4%; 60.8%); and cataract (38.0%; 25.4%). Notably, any-grade invasive second primary malignancies included solid tumors (8.4%; 4.4%) and hematologic malignancies (1.1%; 1.1%).
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