Lower Dexamethasone Dose in Multiple Myeloma: A Multicenter Retrospective Analysis

Background/Objectives: Dexamethasone has long served as the cornerstone of therapy for multiple myeloma; however, its optimal dosing remains ill-defined, particularly when balanced against its profound toxicity profile. Recent therapeutic advances have consequently intensified interest in steroid dose-reduction strategies. This retrospective, multicenter study aimed to evaluate the impact of varied dexamethasone dosing regimens on clinical outcomes within a real-world setting. Methods: We conducted a retrospective multicenter study across 11 Hungarian centers, enrolling 272 patients with multiple myeloma who received lenalidomide–dexamethasone therapy. Treating physicians determined dosing strategies at their discretion for each patient. We retrospectively stratified patients into three cohorts based on their prescribed weekly dexamethasone dose: 40 mg, 20 mg, and less than 20 mg. Results: We observed a distinct interaction between patient age and weekly dexamethasone dose. Nonetheless, we detected no statistically significant difference in progression-free survival (PFS) among the three dosing cohorts (p = 0.632). Similarly, dexamethasone dose intensity demonstrated no significant association with overall treatment response (p = 0.560). Subgroup analysis restricted to patients with high-risk cytogenetics also showed no significant disparities in PFS (p = 0.312). Furthermore, early treatment response rates at 2 and 6 months were also independent of the dexamethasone dose. Notably, grade 3–5 adverse events were numerically more frequent in the 40 mg group. The lack of significant differences in these outcome measures is particularly important, given the baseline age imbalances among the cohorts. Conclusions: Lower initial dexamethasone dose was not associated with statistically significant differences in progression-free survival or treatment response in this retrospective cohort. Although Grade 3–5 adverse events were numerically more frequent in the 40 mg group, these observations warrant further investigation in prospective studies.