An open-label, pharmacokinetic study of lenalidomide and dexamethasone therapy in previously untreated multiple myeloma (MM) patients with various degrees of renal impairment – validation of official dosing guidelines

Abstract

Lenalidomide is a backbone agent in the treatment of multiple myeloma, but dose adjustment is required for those with renal impairment (RI). We evaluated the pharmacokinetics (PK) and safety of lenalidomide and dexamethasone as frontline pre-transplant induction, with doses adjusted at start of each cycle based on creatinine clearance, as per the official dosing guidelines. After 4 cycles, PK studies showed that patients with moderate RI (30 ≤ CrCl < 60 mL/min) receiving 10 mg dosing may be under-dosed and those with severe RI (CrCl <30ml/min) appeared appropriately dosed initially, but sustained significant decreases in maximum serum concentration (Cmax) after repeated dosing, due to rapid clinical improvement and enhanced drug clearance. PK drug monitoring during cycle 1 may facilitate appropriate and timely dose adjustments. Adverse events rates did not vary based on severity of RI. No patient discontinued lenalidomide for toxicity. This supports the feasibility and safety of frontline lenalidomide in transplant-eligible patients with RI.

Keywords:

• Lenalidomide
• multiple myeloma
• renal impairment
• pharmacokinetics

Disclosure statement

Dr. Christine Chen reports grants and personal fees from Celgene, personal fees from Janssen, personal fees from Gilead, personal fees from Abbvie, during the conduct of the study. Dr. Donna Reece reports grants and personal fees from Celgene, personal fees from Janssen, personal fees from Takeda, personal fees from Amgen, personal fees from Karyopharm, grants from Otsuka, grants from Merck, grants from Bristol-Myers Squibb, during the conduct of the study. Dr. Trudel reports grants and personal fees from Celgene, grants and personal fees from Amgen, grants and personal fees from GlaxoSmithKline, personal fees from Takeda, grants and personal fees from Janssen, personal fees from Karyopharm, personal fees from Sanofi, grants from Genentech, outside the submitted work. Dr. Kukreti reports personal fees from Celgene, during the conduct of the study; personal fees from Amgen, outside the submitted work. Dr. Tiedemann reports grants from Terry Fox Research Institute, personal fees from Janssen, personal fees from Amgen, personal fees from Celgene, personal fees from Roche, personal fees from Takeda, outside the submitted work. Dr. Prica has nothing to disclose. Yanshuo Cao, Harminder Paul, Lisa W. Le, Olga Levina, Sumeet Kakar, Anthea Lau, Hongzhuan Chen, and Eric Chen have nothing to disclose.

Additional information

Funding

This study received research support from Celgene Corporation [grant no. NCT01270932].