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WM Medical Practice Guidelines & Research

Investigation and management of IgM and Waldenström-associated peripheral neuropathies: recommendations from the IWWM-8 consensus panel. D'Sa, S., Kersten, M. J., Castillo, J. J., Dimopoulos, M., Kastritis, E., Laane, E., Leblond, V., Merlini, G., Treon, S. P., Vos, J. M. and Lunn, M. P. (2017), Br J Haematol. doi:10.1111/bjh.14492
The International Workshops on Waldenström Macroglobulinaemia (IWWM) have proposed criteria for diagnosis and therapy (Owen et al, 2003), response (Owen et al, 2013), and treatment (Dimopoulos et al, 2014) in WM patients. As part of its latest consensus deliberations (IWWM8, London 2014), the panel reviewed the management of peripheral neuropathies associated with IgM monoclonal gammopathies, including WM.  Importantly, a consensus regarding the use of clinical outcome measures and recommended models of care for this group of patients is discussed, as well as appropriate treatment interventions.

Genomics, Signaling, and Treatment of Waldenström Macroglobulinemia. Zachary R. Hunter, Guang Yang, Lian Xu, Xia Liu, Jorge J. Castillo, and Steven P. Treon Journal of Clinical Oncology  2017, 35(9):994-1001. Next-generation sequencing studies have identified highly recurrent somatic mutations in MYD88, CXCR4, ARID1A, and CD79, and other genes, as well as copy number alterations effecting important regulatory genes in chromosome 6q and elsewhere. Transcriptional changes, disease presentation, therapeutic outcome, and overall survival are affected by mutations in MYD88 and/or CXCR4. (Article provided with permission of the Bing Center for Waldenstrom's Macroglobulinemia.)

Ibrutinib for patients with rituximab-refractory Waldenström's macroglobulinaemia (iNNOVATE): an open-label substudy of an international, multicentre, phase 3 trial. Dimopoulos, Meletios A et al. The Lancet Oncology, 2017,18(2):241 - 250. In the era of widespread rituximab use for Waldenström's macroglobulinaemia, new treatment options for patients with rituximab-refractory disease are an important clinical need. Ibrutinib has induced durable responses in previously treated patients with Waldenström's macroglobulinaemia. This study assessed the efficacy and safety of ibrutinib in a population with rituximab-refractory disease. (Article provided with permission of the Bing Center for Waldenstrom's Macroglobulinemia.)

Waldenstrom Macroglobulinemia: 2017 Update on Diagnosis, Risk Stratification, and management. Gertz, MA, Am. J. Hematol. 92:209–217, 2017. This Mayo Clinic clinician provides a technical clinical update of WM, as part of the Annual Clinical Updates in Hematological Malignancies Series from the American Journal of Hematology.

Guidelines for the diagnosis, treatment and response criteria for Bing-Neel syndrome. Minnema  MC. et al. Haematologica, 2017 Volume 102(1):43-51 obtained from the Haematologica Journal website. Bing Neel syndrome is a rare disease manifestation of Waldenstrom’s macroglobulinemia that results from infiltration of the central nervous system by malignant lymphoplasmacytic cells. These technical guidelines describe the clinical symptoms, as well as, the appropriate laboratory and radiological studies that can aid in the diagnosis. A discussion of prospective clinical trials and protocols that employ uniform treatment for delineating treatment outcomes is included.

Treatment Recommendations for Waldenström Macroglobulinemia from the Eighth International Workshop on WM. Leblond, V., et al. Blood, September 8, 2016, Volume 128, Number 10.
These are updated treatment recommendations from the August 2014 International Workshop in London, England. (Article provided with permission of Dr. Steven Treon of the Bing Center for Waldenstrom's Macroglobulinemia.)

Waldenström's Macroglobulinemia: Subtype Review. Lymphoma Coalition, August 2016. This is an overview of the disease prepared by the Lymphoma Coalition with review and editing assistance provided by the IWMF. It covers the basic biology of WM, along with current treatment recommendations from NCCN and from Dr. Steven Treon of the Bing Center for WM. Special sections of this report look at treatment availability and clinical trial activity in multiple countries and discuss the patient experience in terms of physical symptoms and psychological and social factors that impact the patient's sense of well being.

Waldenstrom macroglobulinemia: biology, genetics, and therapy. Paludo J, Ansell SM, Blood and Lymphatic Cancer: Targets and Therapy, 2016, 6:49-58. An excellent review that covers the pathophysiologic understanding of WM in light of the discovery of MYD88 and CXCR4, as well as treatment regimens with a focus on ibrutinib.

Recommendations for the diagnosis and initial evaluation of patients with Waldenström Macroglobulinaemia: A Task Force from the 8th International Workshop on Waldenström Macroglobulinaemia. Jorge J. Castillo et al, British Journal of Haematology, 2016. A multi-institutional task force was formed during the 8th International Workshop for WM in London to develop consensus recommendations for the diagnosis and initial evaluation of patients with WM. In this document, recommendations are provided for history-taking and physical examination, laboratory studies, bone marrow aspiration and biopsy analysis, and imaging studies. Guidance is also provided on the initial evaluation of special situations, such as anemia, hyperviscosity, neuropathy, Bing-Neel syndrome, and amyloidosis. (Article provided with permission of Jorge J. Castillo of the Bing Center for Waldenstrom's Macroglobulinemia.)

How I Treat Waldenstrom Macroglobulinemia. Treon, S. P., Blood. First Edition Paper, prepublished online May 22, 2015, DOI 10.1182. Treatment recommendations published by Dr. Steven Treon of the Dana-Farber Cancer Institute in 2015. (Article provided with permission of the Bing Center for Waldenstrom's Macroglobulinemia.)

NCCN Clinical Practice Guidelines in Oncology for Macroglobulinemia/Lymphoplasmacytic Lymphoma. The NCCN is a non-profit alliance of 27 cancer centers in the U.S. whose goal is to improve the quality and effectiveness of care provided to cancer patients. They provide updated guidelines based on the most current and up-to-date diagnosis and treatment guidelines available. You must establish an account on the NCCN website to login and view these guidelines.

A review of recent advances in the biology of WM and the current therapeutic options for untreated and relapsed WM patients, including a discussion of prognostic factors. Jorge J. Castillo, Irene M. Ghobrial, and Steven P. Treon from Dana-Farber Cancer Institute. Biology, Prognosis, and Therapy of Waldenström Macroglobulinemia. Cancer Treatment and Research, 2015. (Provided with permission from Dr. Castillo).

MYD88 L265P Somatic Mutation in Waldenström’s Macroglobulinemia. Steven P. Treon et al, Dana-Farber Cancer Institute, Boston MA. This article, published in the New England Journal of Medicine in 2012, outlines the seminal discovery of the prevalence of the MYD88 L265 P mutation in WM patients. The research leading to this discovery was funded in part with the support of the IWMF.

Diagnosis and Management of Waldenstrom Macroglobulinemia: Mayo Stratification Macroglobulinemia and Risk-Adapted Therapy (mSMART) Guidelines. Stephen M. Ansell et al, Mayo Clinic. Mayo Clinic researchers provide their recommendations on timing and choice of therapy. These guidelines undergo periodic review and updating.

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