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.     

Treating chronic lymphocytic leukemia with thalidomide and lenalidomide

Introduction: Chronic lymphocytic leukemia (CLL) is biologically, as well as clinically, highly heterogeneous. In CLL patients, immunosuppression is a consequence of the disease, which plays a key role in effecting the quality of life and overall survival. Treatment modalities should ideally not only reduce tumor burden, but also augment immune function in CLL patients.

Areas covered: The current review summarizes biological and clinical data on thalidomide and lenalidomide in CLL.

Expert opinion: Immunomodulatory drugs such as thalidomide and lenalidomide show both antitumor activity and immunostimulation. Three main mechanisms of action seem to play a role in cancer, including i) anti-angiogenic, ii) immunomodulatory and iii) tumoricidal effects. The exact contributions of these effects seem to be unique for different diseases. The two representatives of this family of drugs studied in CLL include thalidomide and its analog lenalidomide. These drugs proved to be effective as single agents and in the combination setting in CLL. Toxicities have been identified but largely controlled by a low starting dose, with gradual dose escalation.     

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.