Abstract
Welcome to the April 2012 issue of Therapeutic Advances in Hematology. Thanks to all of you our steady stream of comprehensive reviews as well as the inclusion of original research continues to serve our purpose to update and enlighten in our area of malignant (and nonmalignant) hematology. We will continue to strive to cover all the facets of hematology and encourage potential authors to submit novel research; all work is closely peer reviewed and each issue balanced to contain a variety of topics. I stand in fine company with our esteemed editorial board and thank them as always for their commissioning and reviewing efforts – we all know how important yet time consuming careful peer review is, and we hold it in the highest of regard at Therapeutic Advances in Hematology.
Our issue commences with an original report from Drs H. Menzel and K. Hinmuller and colleagues from Munich, Germany. They performed a retrospective analysis of the outcome of patients with multiple myeloma, who after initial autologous stem-cell transplantation, have taken advantage of novel agents for the maintenance of remission after first transplant, and subsequently have undergone second ‘late’ autografting at relapse. Using their regimen, results show a favorable time to next treatment, albeit in a small number of patients, proving both the boon of novel agents (e.g. immunomodulatory drugs, proteosome inhibitors), and the utility of sequential transplants in multiple myeloma.
Our next paper is a thoughtful review by Dr E. Estey of the Fred Hutchinson Cancer Research Center on the topic of managing acute myelogenous leukemia (AML) in older patients. The paper begins with a deconstruction of the simple notion that age is a predictor and outlines the key variables predictive of response and outcome (not only age but performance status, early treatment-related mortality, and disease resistance, with the cytogenetic/molecular characterizations of monsoonal karyotype and nucleophosmin/FMS-like tyrosine kinase 3 being crucial). Treatment options are then reviewed, covering hypomethylating agents, lenolidomide, clofarabine, liposomal molar ratio preparations of daunorubicin and ara-C, and reduced intensity transplant. Conclusions are to think critically about patient risk, data available from ‘new’ approaches, and pursue properly designed research into combination and other novel therapies when appropriate.
Dr C. Langer and others from the University Hospital of Ulm, Germany, then cover the intriguing topic of RNA interference. They review the role of microRNAs (miRNAs) as tumor suppressor genes, and the apparent potential therapeutic implications of mimicking this effect when lost. The challenge of delivery and the pitfalls of ‘off-target’ effects are described as well as an example given of the successful use of miRNAs therapeutically in hepatitis C virus infection. This review leaves us encouraged that such a pathway may be ripe for the development of selective, rationally designed therapeutics as the details of cancer genetics continue to unfold.
Dr V. Duong, in conjunction with Dr A. List from the H. Lee Moffitt Cancer Center, Tampa, FL, USA, then review the story of lenolidomide as a highly effective therapy for patients with myelodysplastic syndrome (MDS) and a 5q deletion. They review the pathogenesis of 5q MDS, and highlight the potential role of haplodeficiency of genes such as RPS14, miR-145 and miR-146b (quite nicely related to the miRNA story reviewed by Dr Langer), and the potential therapeutic effect of lenolidomide by inhibiting protein phosphatase 2A (PP2A). Data from the phase II and III trials are summarized together with subtle questions about toxicity including risk of progression to AML, leaving us with a much better understanding of this selective yet still not fully understood therapeutic for hematologic malignancies.
Lastly, Drs M-V Mateos and J. San Miguel from the University Hospital in Salamanca, Spain review the data from the key trials leading to approval for bortezomib, including the single agent phase II trials, SUMMIT and the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), and the randomized phase III Assessment of Proteasome Inhibition for Extending Remissions (APEX) trial. They then review data from a number of combination trials and data supporting upfront use of bortezomib in patients not eligible for stem-cell transplantation. The paper then carefully reviews the data showing noninferiority and potential improvement in toxicity (reduction in peripheral neuropathy) with subcutaneous dosing in lieu of intravenous dosing for bortezomib, with appropriate pause given to the number of questions that remain regarding evolution to this route of administration.
Enjoy!