Factors Associated with Dose Modification of Lenalidomide Plus Dexamethasone Therapy in Multiple Myeloma

Abstract

Long-term combination treatment with lenalidomide and low-dose dexamethasone is important to achieve a curative effect in patients with multiple myeloma (MM). In this study, the plasma concentration of lenalidomide was measured at 3 h after oral administration, when the drug is in the elimination phase and can be easily measured in outpatients, to identify factors that may lead to the discontinuation of this combination therapy. Patients were assigned to continuation or discontinuation of therapy groups, and the baseline characteristics of patients, lenalidomide concentration, and concentration/dose (C/D) ratios reflecting oral clearance were compared between the two groups. The efficacy and severity of adverse events were also compared. The results showed that patients who discontinued or modified treatment had low plasma concentrations of lenalidomide and C/D ratios, indicating high oral clearance of lenalidomide. The estimated creatinine clearance rate was negatively correlated with the C/D ratio. The plasma concentrations of lenalidomide were independent from kidney function and differed significantly among patients. Taken together, the results indicate that low plasma concentrations of lenalidomide and low C/D ratios may lead to discontinuation of combination therapy in patients with MM. This suggests that early measurement of lenalidomide plasma continuation would help to prevent discontinuation of therapy or a delay in modifying the dose of lenalidomide.

Toward Therapeutic Drug Monitoring of Lenalidomide in Hematological Malignancy? Results of an Observational Study of the Exposure-Safety Relationship

“…LEN’s significant activity in hematological malignancy has led to its incorporation into multiple treatment regimens ( Gribben et al, 2015 ), such as the LEN plus rituximab (R 2 ) regimen for NHL ( Leonard et al, 2019 ), as well as regimens based on LEN plus dexamethasone for MM ( Mateos et al, 2013 ). As an oral targeted antineoplastic agent, long-term and continuous LEN treatment is important to achieve a therapeutic effect ( Kado et al, 2020 ).…”