Novel therapeutic agents for the management of patients with multiple myeloma and renal impairment.
Renal impairment is a major complication of multiple myeloma. Patients presenting with severe renal impairment represent a greater therapeutic challenge and generally have poorer outcome. However, once patients with renal impairment achieve remission, their outcomes are comparable with those of patients without renal impairment. Therapies that offer substantial activity in this setting are needed. Bortezomib, thalidomide, and lenalidomide have substantially improved the survival of patients with multiple myeloma. Here we review the pharmacokinetics, activity, and safety of these agents in patients with renal impairment. Bortezomib can be administered at the full approved dose and schedule in renally impaired patients; similarly, no dose reductions are required with thalidomide. The pharmacokinetics of lenalidomide is affected by its renal route of excretion, and dose adjustments are recommended for moderate/severe impairment. Substantial evidence has emerged showing that these novel agents improve outcomes of patients with renal impairment, including impairment reversal. Bortezomib, thalidomide, and lenalidomide (at the recommended doses) are active options for patients with mild to moderate impairment, although limited data are available for thalidomide. Information on lenalidomide-based combinations is still emerging, but the available data indicate considerable activity. Substantial evidence indicates that bortezomib-high-dose dexamethasone with or without a third drug (e.g., cyclophosphamide, thalidomide, or doxorubicin) is an appropriate option for patients with any degree of renal impairment.
Roswell Park Cancer Institute, Buffalo, and Tisch Cancer Institute, Mount Sinai Medical Center, New York, New York, USA.
Asher A
AA
Chanan-Khan
Jesús F
JF
San Miguel
Sundar
S
Jagannath
Heinz
H
Ludwig
Meletios A
MA
Dimopoulos
D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001897:Boronic Acids / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069286:Bortezomib; D003907:Dexamethasone / Q000627:therapeutic use; D006801:Humans; D000077269:Lenalidomide; D009101:Multiple Myeloma / Q000150:complications* / Q000188:drug therapy*; D011719:Pyrazines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D051437:Renal Insufficiency / Q000209:etiology*; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D000077269:Lenalidomide