IMROZ
Trial question
What is the effect of addition of isatuximab to the combination of bortezomib, lenalidomide, and dexamethasone (VRd) in patients with multiple myeloma ineligible for transplantation?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
47.0% female
53.0% male
N = 446
446 patients (209 female, 237 male).
Inclusion criteria: patients aged 18-80 years with newly diagnosed multiple myeloma ineligible for transplantation.
Key exclusion criteria: age > 80 years; ECOG performance-status score > 2; eGFR < 30 mL/min/1.73 m².
Interventions
N=265 isatuximab-VRd regimen (4 induction cycles followed by 4-week cycles of continuous treatment with isatuximab plus bortezomib, lenalidomide, and dexamethasone).
N=181 VRd regimen (4 induction cycles followed by 4-week cycles of continuous treatment with bortezomib, lenalidomide, and dexamethasone).
Primary outcome
Progression-free survival at 60 months
63.2%
45.2%
63.2 %
47.4 %
31.6 %
15.8 %
0.0 %
Isatuximab-VRd
regimen
VRd
regimen
Significant
increase ▲
NNT = 5
Significant increase in progression-free survival at 60 months (63.2% vs. 45.2%; HR 1.67, 95% CI 1.14 to 2.44).
Secondary outcomes
Significant increase in complete response or better (74.7% vs. 64.1%; RR 1.17, 95% CI 0.28 to 2.06).
Significant increase in minimal residual disease-negative status in patients with complete response (55.5% vs. 40.9%; OR 1.8, 95% CI 1.23 to 2.65).
No significant difference in overall survival at 60 months (72.3% vs. 66.3%; HR 1.28, 99% CI 0.68 to 2.44).
Safety outcomes
No significant difference in adverse events leading to discontinuation or serious adverse events.
Conclusion
In patients aged 18-80 years with newly diagnosed multiple myeloma ineligible for transplantation, isatuximab-VRd regimen were superior to VRd regimen with respect to a progression-free survival at 60 months.
Reference
Thierry Facon, Meletios-Athanasios Dimopoulos, Xavier P Leleu et al. Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2024 Oct 31;391(17):1597-1609.
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