Daratumumab-Lenalidomide Regimen Allows Frail Multiple myeloma Patients to Reduce Steroid Use Without Increased Infection Risk
A new study published in Lancet Oncology reveals that patients with multiple myeloma (MM) can safely minimize their use of the steroid dexamethasone – a common component of treatment – without increasing their risk of infection. the findings demonstrate a superior approach to managing the disease, particularly in frail, older patients.
multiple myeloma is the second most common hematologic malignancy, characterized by the overproduction of abnormal B lymphocytes. This can led to serious complications including renal failure, anemia, and weakened bones. While treatment options have advanced, significant challenges remain, especially for older individuals whose frailty can impact their tolerance to aggressive therapies.
“Older patients with newly diagnosed multiple myeloma show variability in their fitness levels and tolerance to treatment, making their management more complex than younger patients,” the study authors wrote. “This heterogeneity necessitates the progress of tailored approaches adapted to different patient subgroups.” They further noted that frail patients often experience worse outcomes due to higher rates of non-hematological adverse events and treatment discontinuations.
Dexamethasone,while effective,carries a risk of adverse effects including infections,hypertension,and hyperglycemia. Prolonged use can significantly impact treatment adherence and overall success, particularly in vulnerable patients.
Researchers conducted a phase 3,randomized,open-label trial – IFM2017_03 (NCT03993912) – to investigate whether a daratumumab and lenalidomide combination,with minimized dexamethasone,could improve outcomes in frail patients newly diagnosed with MM who were ineligible for high-dose chemotherapy and stem cell transplantation. A total of 295 patients (median age 81 years; 51% female, 49% male) were randomized in a 2:1 ratio to receive either subcutaneous daratumumab plus oral lenalidomide with reduced dexamethasone (n=197) or lenalidomide and dexamethasone (n=98).
The primary endpoint of progression-free survival (PFS) was not significantly different between the two groups (median PFS 34.4 months vs. 31.4 months, hazard ratio 0.86, 95% confidence interval 0.65-1.14; P=0.32). Rates of overall response were similar (83% vs.78%, respectively). Importantly, rates of grade 3 or higher neutropenia were lower in the daratumumab-lenalidomide group (16% vs.28%), and rates of infection (19% vs. 21%, respectively). Serious adverse events occured in 126 patients in the dexamethasone-sparing group and 66 in the control group. Deaths related to treatment occurred in 23 patients (12%) in the dexamethasone-sparing group and 12 patients (13%) in the control group.
By demonstrating that dexamethasone can be minimized without compromising efficacy or increasing infection risk, the IFM2017-03 trial supports a shift towards individualized, steroid-sparing approaches in the treatment of multiple myeloma. As the population of older patients with MM continues to grow,these regimens promise to improve both longevity and quality of life while reducing the burden of treatment-related toxicity.
References:
- Salomon M, Lambert J, Hulin C, et al. Safety and efficacy of a dexamethasone-sparing regimen with daratumumab and lenalidomide in patients with frailty and newly diagnosed multiple myeloma (IFM2017-03): a phase 3, open-label, multicentre, randomised, controlled trial. Lancet Oncology.october 2025. doi: 10.1016/S1470-2045(25)00280-3
- Compare Lenalidomide and Subcutaneous Daratumumab vs Lenalidomide and Dexamethasone in Frail Subjects With Previously Untreated multiple Myeloma Who Are Ineligible for High Dose therapy (IFM2017_03). Updated September 11, 2025. Accessed October 7, 2025. https://clinicaltrials.gov/study/NCT03993912
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