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Incidence, risk factors, and implemented prophylaxis of varicella zoster virus infection, including complicated varicella zoster virus and herpes simplex virus infections, in lenalidomide-treated multiple myeloma patients

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Abstract

In the era of high-dose chemotherapy and novel antimyeloma agents, the survival of multiple myeloma (MM) patients has substantially improved. Adverse effects, including infections, may however arise in the era of combination antimyeloma therapies. In general, MM patients have shown a risk of varicella zoster virus (VZV) infection of 1–4 %, increasing with bortezomib treatment or transplants, but whether immunomodulatory drugs also bear a risk of VZV/complicated herpes simplex virus (HSV) (e.g., VZV-encephalitis [VZV-E], disseminated VZV-infection [d-VZV-i], or conus-cauda syndrome [CCS]) has not been elucidated. We here assessed VZV, VZV-E, d-VZV-i, and CCS in 93 lenalidomide-treated MM patients, consecutively seen and treated in our department. Patients’ data were analyzed via electronic medical record retrieval within our research data warehouse as described previously. Of the 93 MM patients receiving lenalidomide, 10 showed VZV or other complicated VZV/HSV infections. These VZV patients showed defined risk factors as meticulously assessed, including suppressed lymphocyte subsets, substantial cell-mediated immune defects, and compromised humoral immune response. Due to our findings—and in line with an aciclovir prophylaxis in bortezomib and stem cell transplant protocols—we introduced a routine aciclovir prophylaxis in our lenalidomide protocols in May 2012 to minimize adverse events and to avoid discontinuation of lenalidomide treatment. Since then, we have observed no case of VZV/complicated HSV infection. Based on our data, we encourage other centers to also focus on these observations, assess viral infections, and—in those centers facilitating a research data warehouse—advocate an analogue data review as an appropriate multicenter approach.

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Acknowledgments

We are thankful for the very valuable recommendations from Prof. Dr. Markus Manz, Zürich, Prof. Dr. Jürgen Ruland, München, PD Dr. Florian Bassermann, München, Prof. Dr. Justus Duyster, Freiburg, Prof. Dr. Mark Israel, Lebanon, NH, USA, and Prof. Dr. Werner Vach, Department of Medical Biometry and Statistics, University Medical Center, Freiburg, Germany. The authors also thank Prof. Dr. Angela Dispenzieri, Mayo Clinic, USA and Prof. Dr. Hermann Einsele, Würzburg for critically reading the manuscript and useful discussion. We are also indebted to Carole Cürten for proof reading and the anonymous internal reviewers of our department for their comments. This work was supported by the Deutsche Krebshilfe (grant 109569 to ME, MK, and RW).

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Supported by the German Cancer Aid (Deutsche Krebshilfe #109569 to ME, MK, and RW).

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Correspondence to M. Engelhardt.

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König, C., Kleber, M., Reinhardt, H. et al. Incidence, risk factors, and implemented prophylaxis of varicella zoster virus infection, including complicated varicella zoster virus and herpes simplex virus infections, in lenalidomide-treated multiple myeloma patients. Ann Hematol 93, 479–484 (2014). https://doi.org/10.1007/s00277-013-1951-6

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  • DOI: https://doi.org/10.1007/s00277-013-1951-6

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