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

Abstract

Multiple myeloma (MM) is a plasma cell malignancy characterized by the presence of monoclonal immunoglobulin and related end-organ damages [1]. Lenalidomide is one of the most potent immunomodulatory drugs (IMiDs) that induce significant anti-tumor effects in patients with newly diagnosed and refractory MM [2–5]. 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]. The clinical relevance of such immunomodulatory effects is yet to be elucidated in patients with MM. Here, we report two patients with relapsed MM who showed transient inflammatory reaction during lenalidomide plus reduced-dose dexamethasone therapy. Case 1 A 49-year-old male was suffering from MM (IgGj type) in stage IIA and international staging system (ISS) 2. He was treated with three courses of vincristine, adriamycin, and dexamethasone (VAD); however, his disease activity was not improved. He received two courses of BD therapy (bortezomib 1.3 mg/m on days 1, 4, 8, and 11, and dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12), and achieved very good partial response (VGPR). One month later, he experienced grade 3 peripheral neuropathy and further BD therapy was discontinued. Peripheral blood stem cells (PBSC) were harvested, but he was followed-up without transplantation due to persistent peripheral neuropathy. Two years later, serum IgG levels were gradually increased, and he was referred to our hospital. Laboratory examination revealed that Hb level was 14.0 g/dl and serum total protein 10.0 g/dl with 36.3% M-protein (3.63 g/dl). Bone marrow was normocellular with 13.2% MM cells. As salvage therapy, he received lenalidomide (25 mg on days 1–21) plus dexamethasone (20 mg on days 2, 9, and 16) therapy on a 28-day cycle, but the dosage and frequency of dexamethasone was reduced because of hypertension and skin acne (Fig. 1a). On day 8 at cycle 1, serum CRP level was suddenly increased to 6.32 mg/dl and decreased to 0.85 mg/dl on day 12 after administration of dexamethasone, but re-elevated to 8.37 mg/dl on day 15. Plasma fibrinogen level was also increased up to 916 mg/dl, but white blood cell count remained normal range. He experienced grade 1 dry skin and fatigue as adverse events, but there were no signs and symptoms of infection or inflammation such as fever and arthralgia. We carefully continued the treatment, and serum CRP and plasma fibrinogen levels became unremarkable during subsequent therapeutic cycles. His serum total protein was gradually decreased to 6.7 g/dl with 11.2% M-protein (0.75 g/dl) achieving PR after 4 cycles of the therapy. Case 2 A 58-year-old male was admitted to our hospital because of compression fracture in lumbar vertebrae. He S. Ozaki (&) T. Harada S. Fujii S. Nakamura H. Miki A. Nakano K. Kagawa K. Takeuchi M. Abe T. Matsumoto Department of Medicine and Bioregulatory Sciences, The University of Tokushima Graduate School of Health Biosciences, 3-18-15 Kuramoto, Tokushima 770-8503, Japan e-mail: ozakishu@clin.med.tokushima-u.ac.jp