A recent study has shown that a treatment regimen combining daratumumab, lenalidomide, and a limited dose of dexamethasone significantly improves progression-free survival in older and frail patients newly diagnosed with multiple myeloma. The findings, published in Lancet Oncology, stem from the phase 3 IFM2017-03 trial (NCT03993912) and indicate a promising alternative to traditional therapies.
At a median follow-up of 46.3 months, patients receiving the dexamethasone-sparing treatment (n = 200) experienced a median progression-free survival (PFS) of 53.4 months, compared to 22.5 months for those treated with lenalidomide plus continuous dexamethasone (n = 95). The hazard ratio was calculated at 0.51, with a 95% confidence interval of 0.37-0.70, suggesting a significant survival advantage (P < .0001). The study's lead author, Salomon Manier, MD PhD, an associate professor at the University Hospital of Lille in France, emphasized the necessity of adapting treatment strategies for older patients due to their varying levels of fitness and treatment tolerance. He noted that frail patients often face higher risks of non-hematologic adverse effects and treatment discontinuation.
Patients enrolled in the study were at least 65 years old and had newly diagnosed multiple myeloma, with a frailty score of at least 2. The trial was structured to assess the effectiveness of the dexamethasone-sparing regimen, in which dexamethasone was limited to the first two treatment cycles, thereby reducing exposure to associated side effects such as infections and hypertension.
In the experimental group, patients received subcutaneous daratumumab at 1,800 mg during the first two cycles, followed by less frequent dosing. They also received lenalidomide at 25 mg on days 1 to 21 of a 28-day cycle, alongside dexamethasone at 20 mg for the first two cycles. Conversely, the control group continued with lenalidomide plus dexamethasone throughout their treatment.
The study’s primary endpoint was PFS, while secondary endpoints included overall survival (OS), overall response rate (ORR), and safety profiles. The results revealed that patients in the dexamethasone-sparing group achieved an ORR of 92%, compared to 85% in the control group. Notably, the rate of achieving very good partial response (VGPR) or better was 69% for the experimental group versus 51% for controls.
Regarding safety, the rates of any-grade adverse events (AEs) were similar between the two groups, with both at 98%. Serious AEs occurred in 63% of the dexamethasone-sparing group and 69% of the control group. Notably, AEs led to treatment discontinuation in 30% of the experimental arm versus 34% in the control arm.
Manier and his colleagues highlighted that despite the challenges of managing older patients with multiple myeloma, the findings underscore the potential of the daratumumab/lenalidomide combination to offer a safer and more effective treatment option. The trial not only demonstrated the efficacy of this approach but also confirmed that the addition of the anti-CD38 antibody daratumumab did not increase toxicity compared to standard care.
These results may shift the treatment paradigm for older patients with multiple myeloma, paving the way for broader adoption of this dexamethasone-sparing regimen in clinical practice.