Treatment of plasma cell dyscrasias with lenalidomide

Abstract

Lenalidomide is an immunomodulatory drug, structurally related to thalidomide, with pleiotropic activity including antiangiogenic and antineoplastic properties. It is the product of advances in our understanding of the biology of myeloma cells, their interactions with the microenvironment and of the underlying molecular pathways. In preclinical and clinical studies, lenalidomide was more potent and less toxic than thalidomide. Subsequent phase II and III studies confirmed the activity of lenalidomide either as a single agent or in combination with dexamethasone in relapsed or refractory myeloma patients, whereas combinations with chemotherapy induce high response rates and durable remissions. Lenalidomide has been used successfully as an upfront treatment either with high or low dose dexamethasone or with melphalan and prednisone, resulting in high overall response and complete response rates and excellent 1-year survival. Lenalidomide causes less neuropathy than thalidomide; however, the risk of thromboembolism is high, especially in patients treated with lenalidomide and steroids. In this review, we summarize the mechanisms of action, toxicity and clinical activity, and the current role of lenalidomide in patients with multiple myeloma or other related plasma cell disorders.

Kidney Disease and Multiple Myeloma

“…Lenalidomide needs to be used with caution in the setting of CKD, and dose reduction is mandatory, because the drug is renally cleared. Despite this information, myelosuppression and other adverse events are more common in this setting (76)(77)(78). Nonetheless, it is not directly nephrotoxic, and therefore, a low dose (e.g., 5-10 mg/d) can be used.…”

“…These agents have complex mechanisms of action that include the interruption of myeloma cell growth and disruption of myeloma and bone marrow stromal cell interactions (75,76). Lenalidomide needs to be used with caution in the setting of CKD, and dose reduction is mandatory, because the drug is renally cleared.…”

Untitled

“…Other studies done by Rajkumar SV et al, 11 and Falco et al 16 also have reported incidence of constipation with Len-Dex regimen. The incidence of constipation in Len-Dex regimen was about 27% in the study conducted by Dimopoulos MA et al, 17 . Constipation was reported in patients on VAD regimen in study by Zhongguo Shi Yan Xue Ye Xue Za Zhi 18 .…”

Trends in day 100 and 2-year survival after auto-SCT for AL amyloidosis: outcomes before and after 2006

“…[20][21][22] Efforts to improve survival in patients with amyloidosis have been facilitated by the introduction of novel agents for the treatment of amyloidosis, including thalidomide, 23 lenalidomide 24 and bortezomib. 25 Melphalan-dexamethasone has been established as a highly effective regimen in patients who are not considered candidates for auto-SCT.…”