Expert review of hematology
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In spite of significant advances in the management of multiple myeloma (MM), the disease remains incurable and nearly all patients ultimately relapse and require salvage chemotherapy. As such, relapsed and relapsed-refractory MM remains a critical area of research pertaining to biological mechanisms of progression and chemotherapy resistance, as well as to the development of new pharmacologic agents and immunologic approaches for the disease. The immunomodulatory agents and proteasome inhibitors represent the cornerstone of treatment in this setting, with combination regimens incorporating these drugs demonstrating encouraging rates and duration of response, including the newer agents, pomalidomide and carfilzomib. In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat.
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Effective therapy for multiple myeloma has existed for a little more than the last half century. The introduction of melphalan 55 years ago was followed by a stagnant period of four decades in which many combinations of alkylating agents and chemotherapeutic drugs were developed without a significant increase in overall survival. The first novel agent, thalidomide, was introduced 15 years ago when it was used as an anti-angiogenesis agent. ⋯ Then lenalidomide, a second-generation analog of thalidomide was introduced. More recently carfilzomib, a proteasome inhibitor, and pomalidomide, a third-generation derivative of thalidomide have entered the marketplace. Many new agents are in development and potentially available for future therapy.
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The risk of CNS dissemination and CNS prophylaxis strategies in aggressive non-Hodgkin lymphoma (NHL) is still debated. CNS dissemination is a rare but fatal event. ⋯ Risk models in the rituximab era were modulated for the detection of occult CNS disease at diagnosis using flow cytometry. The optimal regimen for CNS prophylaxis in aggressive lymphoma patients has not been established thus far and should be modulated at different levels of 'intensity' such as standard intrathecal chemotherapy, 'active' intrathecal chemotherapy with liposomal cytarabine or more aggressive systemic treatment with high doses of drugs having good CNS bioavailability reserved for patients who are truly at high risk of CNS dissemination.
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Drugs that selectively inhibit Bruton's tyrosine kinase (BTK), such as the new orally administered agent ibrutinib, are currently under investigation for the treatment of several types of B-cell malignancies. In this article, the authors present results of a Phase Ib/II study of ibrutinib in 85 patients with relapsed or refractory chronic lymphocytic leukemia (CLL). ⋯ In addition, the use of an effective oral agent like ibrutinib whose efficacy does not translate into a high burden of toxicity should be considered in choosing therapy in the elderly. A challenging issue with ibrutinib is the possibility of overcoming chemotherapy in the treatment of CLL.
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Intravenous (iv.) iron is now the recommended treatment for iron deficiency anemia if oral preparations have failed or in those undergoing hemodialysis. Iron isomaltoside is a new iv. iron preparation, licensed since 2009 in the UK and Europe. The iron is tightly bound within a nonionic isomaltoside carbohydrate matrix, as opposed to most other iv. iron preparations that use branched polymers to form a carbohydrate shell. ⋯ Currently, there remains limited data on efficacy, safety and cost-effectiveness. Although initial data are encouraging, they come from only three published small trials, thus restricting the conclusions that can be made. Future research needs to concentrate on comparative analyses with other iv. iron therapies.