Lenalidomide in the management of eosinophilic dermatosis of hematological malignancy

Eosinophilic dermatosis of hematological malignancy is a paraneoplastic skin eruption associated with chronic lymphocytic leukemia and other B‐cell malignancies. It clinically resembles an insect bite reaction and it can precede the symptoms of the hematological malignancy or be related to a more aggressive course. Different treatments have been proposed, but partial response and recurrence are frequent. Herein, we describe a case of eosinophilic dermatosis associated with mantle cell lymphoma with remission after lenalidomide therapy.     

Immunomodulatory treatment for mucosa-associated lymphoid tissue lymphoma (MALT lymphoma)

The pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphoma has been characterized as a dynamic process driven by lymphoma cell dependency on T-cell signaling, chronic antigenic stimulation of marginal zone B-cells and activation of the nuclear factor-kappa B signaling pathway. This concept is underlined by the strong causal connection of chronic Helicobacter pylori associated gastritis and MALT lymphoma development based on perpetual auto-antigenic stimulation of Helicobacter pylori-specific T-cells, but also its association with further potential infectious triggers and autoimmune disorders for extragastric lymphoma sites. Thus, given the dependency of MALT lymphoma cells on the tumor microenvironment, this specific entity appears highly suitable for immunomodulatory treatment strategies. Several approaches have been assessed in the last years including promising data on immunomodulatory agents “IMiDs” thalidomide and lenalidomide, macrolide antibiotics and antibodies. The aim of the present review is to discuss rationales for immunomodulatory therapies in MALT lymphoma and to present the statu quo on immunomodulatory and therefore chemotherapy-free treatment strategies for these patients.     

An update on the use of lenalidomide for the treatment of multiple myeloma

Introduction: Lenalidomide, an immunomodulatory agent with unique mechanism of action, represents the cornerstone in the treatment of patients with multiple myeloma (MM) providing rapid and sustained control of the disease with a manageable safety profile.

Areas covered: This review article, synthesizing all available data coming from trials and evaluating the efficacy and safety of lenalidomide in patients with MM, tries to provide to the clinicians with an easy-to-grasp synopsis of recent and clinically meaningful advances on the field.

Expert opinion: Lenalidomide combined with dexamethasone is a safe and effective option for newly diagnosed MM patients ineligible for autologous stem cell transplantation (ASCT). Long-term administration of the agent as continuous treatment for ineligible for ASCT patients or maintenance therapy after ASCT has documented unprecedented progression-free survival improvements, whereas lenalidomide in combination with dexamethasone has shown deep and durable remissions for patients with relapsed and/or refractory disease.     

Immunomodulatory drugs in multiple myeloma: from molecular mechanisms of action to clinical practice

Multiple myeloma (MM) is a clonal disorder of plasma cells that is considered incurable using the currently available treatments. Cytogenetic, molecular and proteonomic techniques have contributed toward a better understanding of the pathophysiology and prognostic factors of this heterogeneous malignancy, whose management has rapidly evolved over the years. The introduction of thalidomide, and the development of safer and more effective thalidomide analogues, represents the major therapeutic advances. Thalidomide, initially used in the treatment of MM because of its angiogenic properties, has considerable therapeutic activity (alone or in combination with other drugs) at all stages of the disease. However, a number of new analogues, such as lenalidomide and pomalidomide, have been developed and are known as “immunomodulatory drugs” (IMIDs). Although they are analogues of thalidomide, they have direct anti-tumor properties, a better tolerability profile and specific activity in both relapsing refractory MM and newly diagnosed disease. The mechanisms of action of IMIDs are still being investigated, but recent studies suggest that, in addition to their anti-angiogenic activity, they have anti-inflammatory and immunomodulatory properties, and directly and indirectly target tumor activity by interfering with various components of the bone marrow (BM) micro-environment. In this paper, we review the pharmacology, mechanisms of action, pre-clinical and clinical efficacy, and the current status of IMIDs in the treatment of MM.     

Prognostic indicators of lenalidomide for multiple myeloma: consensus and controversy

The long-term outcome of multiple myeloma (MM) has been greatly improved through new agents, one being lenalidomide (LEN). Based upon the findings of in vitro experiments, its mode of action against MM occurs through a combination of direct tumoricidal effects on myeloma cells, modulatory effects on tumor immunity and tumor microenvironment-regulatory effects. However, it has not been clearly defined whether the clinical response and long-term outcome of MM with LEN treatment truly reflect the mechanisms of action of LEN proposed by in vitro studies. To ascertain what is known and what remains to be elucidated with LEN, we review the current literature on the mode of action of LEN in association with myeloma pathophysiology, and discuss the prognostic indicators in the treatment of MM with LEN.     

Real‐world health care costs of relapsed/refractory multiple myeloma during the era of novel cancer agents

What is known and objective: High costs of novel agents increasingly put pressure on limited healthcare budgets. Demonstration of their real‐world costs and cost‐effectiveness is often required for reimbursement. However, few published economic evaluations of novel agents for multiple myeloma exist. Moreover, existing cost analyses were heavily based on conventionally treated patients. We investigated real‐world health care costs of relapsed/refractory multiple myeloma in Dutch daily practice. Methods: A retrospective medical chart review was conducted for 139 patients treated between January 2001 and May 2009. Total monthly costs attributable to each cost component were described across all regimens and for bortezomib‐, thalidomide‐ and lenalidomide‐based treatment regimens. Results: Mean monthly total costs (€3,981) varied depending on the sequence of therapy (range: €442–€31,318). Significant cost drivers across all regimens included costs of therapy and hospital admissions. The acquisition costs for novel agents in particular accounted for 32% of mean total monthly costs. Prognostic factors associated with increased mean total monthly costs in multivariate regression analysis included low platelet counts (P = 0·01) and worsening performance status (P < 0·001). Mean total monthly costs of bortezomib‐ and lenalidomide‐based regimens were significantly higher than those for thalidomide‐based regimens in second, third and fourth treatment line. What is new and conclusions: Real‐world costs during treatment of relapsed/refractory multiple myeloma vary greatly. Cost drivers include hospital admissions and acquisition costs of novel agents. Costs also vary by prognostic factors and treatment‐related resource use. Future studies assessing the costs of combination therapy consisting of two or more novel agents are encouraged.