Lenalidomide plus dexamethasone treatment in Japanese patients with relapsed/refractory multiple myeloma

Abstract

We conducted a multicenter, open-label study to investigate the safety, efficacy, and pharmacokinetics of lenalidomide in Japanese patients with relapsed or refractory multiple myeloma The study was composed of the "monotherapy phase", a dose-escalation phase, to determine the tolerability to single agent lenalidomide and the "combination phase" to determine the safety and obtain preliminary data on the efficacy of lenalidomide plus dexamethasone. The primary end points were the tolerability to 25 mg lenalidomide and safety. Nine and six patients were enrolled in the monotherapy phase and the combination phase, respectively. Since 25 mg of monotherapy treatment did not satisfy the DLT criteria, this dose was employed in the combination phase. The major adverse event was myelosuppression. At the planned interim analysis (median study duration, 26.3 weeks), grade 3 or grade 4 neutropenia was observed with high frequency (66.7%). However, all adverse events observed were clinically manageable. In the combination cohort, the overall response rate (> or =PR) was 100%. The pharmacokinetics of lenalidomide showed rapid absorption and elimination after both single and multiple doses. In conclusion, 25 mg of lenalidomide was given safely as a single agent or in combination with dexamethasone in Japanese patients. The good efficacy of the combination therapy was also demonstrated in this study.

Patient with Refractory Multiple Myeloma Developing Eosinophilia after Lenalidomide Treatment and Lung Cancer 9 Months Later: Case Report and Review of the Literature

“…Richter et al [12] reported that lenalidomide activates NK/ T cells, thereby inducing eosinophilia. The MM-017 (n = 15) [1] and MDS-007 (n = 11) [2] studies, which are clinical studies conducted on Japanese patients, found one and five cases of lenalidomide-induced eosinophilia, respectively. However, among clinical studies conducted in countries other than Japan, the MDS-001 study (n = 43) [6] and a pilot study of concurrent lenalidomide and radiotherapy for glioblastoma multiforme (n = 23) [7] found three cases and one case, respectively, of lenalidomide-induced eosinophilia, whereas the MM-009/010 (n = 353) [3,4] and MDS-004 (n = 69) [5] studies found no such cases.…”

“…Eosinophilia during treatment with lenalidomide is rare, with only 19 cases reported to date [1][2][3][4][5][6][7][8][9][10][11]. Of these, only five patients were under treatment with the drug for multiple myeloma.…”

Pharmacokinetics and Tissue Disposition of Lenalidomide in Mice

“…The authors evaluated a Michaelis-Menten function to describe this perceived nonlinearity, but ultimately utilized a dose-proportional model which fit the data equally well. In addition to humans (21,23,24,28), pharmacokinetic studies of lenalidomide have been reported in rats and monkeys (3,29).…”

Transient inflammatory reaction during lenalidomide plus reduced-dose dexamethasone therapy in two patients with relapsed multiple myeloma

“…Lenalidomide is one of the most potent immunomodulatory drugs (IMiDs) that induce significant anti-tumor effects in patients with newly diagnosed and refractory MM [2][3][4][5]. This agent also has pleiotropic properties including immunomodulatory and anti-inflammatory effects, and has been shown to stimulate T cells and NK cells to produce Th1 type cytokines such as interleukin (IL)-2 and interferon-c, while displaying inhibitory effects on the production of Th2 type cytokines and pro-inflammatory cytokines such as IL-4, IL-6, and tumor necrosis factor a (TNF-a) in vitro [6].…”

“…Lenalidomide is commonly used in combination with either high-dose dexamethasone (40 mg/day, days 1-4, 9-12, [2][3][4][5]. These combination therapies induce marked clinical response in MM patients; however, adverse events related to immunomodulatory properties have not been reported probably because of anti-inflammatory effects of dexamethasone.…”