Guidelines on the diagnosis and management of multiple myeloma 2005

In 2001, guidelines for the diagnosis and management of myeloma were published by the Guidelines Working Group of the UK Myeloma Forum (UKMF) on behalf of the British Committee for Standards in Haematology (BCSH) (UK Myeloma Forum; British Committee for Standards in Haematology, 2001). That same year, the second edition of guidelines prepared by the Nordic Myeloma Study Group (NMSG) in 1995 was issued (in the Scandinavian languages; http://www.myeloma-nordic.org). As both sets of guidelines were intended to be evidence based, it was reassuring to note that the recommendations were similar. Subsequently, informal contact between members of the two groups led to the decision to prepare these common, updated guidelines. These revised and updated guidelines include new sections on imaging and the management of skeletal disease, cover new developments in disease classification and staging and the use of new therapeutic approaches, such as thalidomide, bortezomib and reduced-intensity allogeneic transplantation. The guidelines are presented in specific sections as follows: The production of these guidelines involved the following steps: Establishment of working groups on the various topics, with representatives from both organisations. Reappraisal of existing UK and Nordic guidelines from 2001. Review of key literature to 30 November 2004 including Cochrane database, Medline and Internet searches; key references subsequent to this date incorporated in final drafting where relevant. Review of major conference reports. Recommendations based on literature review and consensus of expert opinion. Consultation with representatives of other specialties. Involvement of patient advocacy through the International Myeloma Foundation (UK). Review by UKMF Executive, BCSH Committee and regional coordinators of the NMSG. Review by a sounding board group of 100 members of the British Society for Haematology (BSH). These guidelines set out the key areas of strategy for the effective clinical management of myeloma. Levels of evidence and grades of recommendation are summarised in Tables I and II. Detailed chemotherapy protocols and dosages are not included; they are beyond the scope of this document. Provision of the detailed information and local protocols needed for the safe organisation, delivery and management of chemotherapy and related clinical care are the responsibility of each cancer centre/network (or equivalent in other countries). Statements appearing on drug dosage in the text mainly concern dosages used in specific trials or in the context of adjustment for renal impairment. The authors of these guidelines have made extensive efforts to ensure that treatments, drugs and dosage regimens are accurate. However, changes in information resulting from continuing research and clinical experience, reasonable differences in opinions among authorities, and the possibility of human error in preparation of the text require the clinician to exercise individual judgement when making a clinical decision. He/she must check product information and drug dosages before prescribing or administration. Contributory authors are listed in Appendix 1. Updates of these guidelines will be available on the BSH, BCSH, UKMF and NMSG web sites. A full revision is planned for 2008/09. Myeloma is a plasma cell tumour with an annual incidence in the UK and Scandinavian countries of approximately 50 per million and a median age at presentation of about 70 years (Turesson et al, 1984; Hjorth et al, 1992; Office of National Statistics, 2001; Phekoo et al, 2004). Myeloma has a higher incidence in Afro-Caribbean ethnic groups compared with Caucasians; little else is known specifically about its epidemiology. Most cases present de novo; a minority evolve from Monoclonal Gammopathy of Undetermined Significance (MGUS). Approximately 15% of patients are aged 20 years. Analysis of prognostic factors is essential to compare outcomes within and between clinical trials. For individual patients the best staging systems can predict survival outcome with around 70% sensitivity and specificity. Whether staging systems can beneficially influence choice of therapy is unproven. High serum levels of β2-microglobulin and C-reactive protein and low-serum levels of albumin correlate with worse survival (Bataille et al, 1992; Jacobson et al, 2003). Atypical plasma cell morphology and high proliferative activity also indicate a bad prognosis (Greipp et al, 1993). Cytogenetic abnormalities are strong prognostic factors. Deletions/monosomy of chromosome 13, non-hyperdiploidy and certain balanced translocations, t(4;14), t(14;16), have a strong negative impact on prognosis (Fonseca et al, 2004). Gene profiling with microarray techniques can be expected to expand our knowledge in this field. Many attempts to construct prognostic models have been made since the Durie/Salmon staging system was devised (Durie et al, 2003). has also recently been shown to be helpful in monitoring response in the majority of patients with an immunoglobulin paraprotein; because of the of this may provide an of response to therapy than changes in paraprotein et al, 2004). The of imaging in the management of myeloma the assessment of the extent and of the disease at the and of and subsequent assessment of disease and MRI are examination techniques in myeloma. tomography imaging with and imaging are scanning techniques under current evaluation. The use of X-ray scanning has not been in myeloma. the availability of more imaging it is important to which are most all times the investigation and of a patient, the of a imaging investigation the that it will alter should be Provision of clinical information to the when the imaging is made will ensure that the imaging is performed at the The skeletal survey the for radiological screening at diagnosis, with clear association between the extent of disease and tumour at diagnosis (Durie et al, et al, et al, MRI of the in patients with myeloma may predict a higher risk of than patients who have normal appearances et al, but not predict the of et al, resonance imaging is an essential investigation in the diagnosis of solitary plasmacytoma and myeloma. In the staging of apparently solitary bone magnetic resonance screening of the and lesions that are in to of patients et al, 1993). The diagnosis and management of solitary plasmacytoma have been reviewed in a recent BCSH (Soutar et al, 2004). Standard bone has a low sensitivity in myeloma to the of activity that the lytic lesions of myeloma (Bataille et al, et al, it may of disease not by in the or but is more A number of indicate that scanning can be useful in of disease in myeloma and solitary plasmacytoma et al, et al, 2002; et al, 2003). This is the for level IV evidence). should be used to clarify the significance of such as lytic in of the skeleton that are to on such as and (grade B recommendation; level III evidence). should also be used to symptomatic areas of the skeleton where no is found on the skeletal survey (grade B recommendation; level or MRI is indicated to the and extent of tissue disease and these two imaging techniques can information (grade B recommendation; level III evidence). biopsy may be where appropriate by scanning (grade B recommendation; level III evidence). MRI is the of choice for investigation of patients with a presentation suggestive of cord (grade B recommendation; level evidence). MRI of the should be performed in patients with an apparently solitary plasmacytoma of bone of of the (grade C recommendation; level IV evidence). Bone has no in the routine investigation of myeloma (grade C recommendation; level IV evidence). scanning has no in the routine management of myeloma (grade C recommendation; level IV evidence). bone lesions in patients that X-rays are of a little or no value in disease the of new lytic lesions or increase in of an existing one of disease (Table Symptomatic areas should specifically be It is essential that be compared with relevant disease progression within 3 months of the skeletal in the absence of new skeletal symptoms, a new skeletal survey is unlikely to provide additional Bone is with or MRI may be for of symptomatic areas where no is on the MRI can to to disease from that to et al, 2001; et al, 2004). It is not to repeat a skeletal survey at the time of progression, or not there is clinical evidence of progression of bone disease.