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Ferrata Storti Foundation
Haematologica 2020 Volume 105(7):1780-1790
Multiple myeloma with central nervous system relapse
Philip A. Egan,1 Patrick T Elder,2 W. Ian Deighan,3 Sheila J.M. O’Connor4 and H. Denis Alexander1
1Northern Ireland Centre for Stratified Medicine, Ulster University, Derry/Londonderry, Northern Ireland; 2Department of Haematology, North West Cancer Centre, Altnagelvin Area Hospital, Derry/Londonderry, Northern Ireland; 3Department of Clinical Chemistry, Altnagelvin Area Hospital, Derry/Londonderry, Northern Ireland and 4Haematological Malignancy Diagnostic Service, St James's Institute of Oncology, Leeds, England, UK
ABSTRACT
Central nervous system involvement in multiple myeloma is a rare complication but carries a very poor prognosis. We provide a review of current literature, including presentation, treatment and survival data, and describe our experience in a regional hematologic malignancy diagnosis center where, over a 15-year period, ten cases were identified. Although the median age of onset, frequently between 50-60 years, is comparatively young, those diagnosed usually have a preceding diagnosis of multiple myeloma and often have had several lines of treat- ment. We discuss putative underlying factors such as prior treatment and associations including possible risk factors and features suggestive of a distinct biology. Central nervous system involvement may be challenging to diagnose in myeloma, displaying heterogeneous symptoms that can be confounded by neurological symptoms caused by the typical features of myeloma or treatment side-effects. We discuss the clinical features, imag- ing and laboratory methods used in diagnosis, and highlight the impor- tance of considering this rare complication when neurological symptoms occur at presentation or, more commonly, during the disease pathway. In the absence of clinical trial data to inform an evidence-based approach to treatment, we discuss current and novel treatment options. Finally, we propose the establishment of an International Registry of such cases as the best way to collect and subsequently disseminate presentation, diag- nostic and treatment outcome data on this rare complication of multiple myeloma.
Introduction
Extramedullary disease (EMD) occurs in up to 5% of multiple myeloma (MM) patients, arising via hematogenous spread or through the bone cortex into contigu- ous tissues.1,2 It can occur in the skin, lymph nodes, abdominal organs, upper air- way and the central nervous system (CNS).3 Plasma cell leukemia (PCL) and extramedullary solitary plasmacytomas are biologically and prognostically distinct conditions and therefore not referred to as EMD.2,4 The reported incidence of EMD has increased, possibly in part due to improved survival in MM patients through the use of enhanced treatment modalities, in particular stem cell transplantation (SCT), proteasome inhibitors (PI), and immunomodulatory drugs (IMiD).2 According to one study, there has been an increase in EMD detected at the time of MM diagnosis from 4% to 12% between 1971-93 and 2000-2007 patient cohorts, suggesting improved detection by modern imaging techniques.5 Since it represents a minority of MM cases, clinical trials have not focused on EMD or any of its sub- types such as MM with CNS involvement (CNS-MM), and thus available data come from single cases and small retrospective studies.6
Multiple myeloma with CNS involvement is a rare form of EMD characterized by plasma cell infiltration of the CNS, meninges or cerebrospinal fluid (CSF). It is observed in a small number of MM cases at diagnosis and around a fifth of extramedullary relapses, typically two or three years after the initial MM
Correspondence:
H DENIS ALEXANDER
d.alexander@ulster.ac.uk
Received: February 3, 2020. Accepted: April 14, 2020. Pre-published: May 15, 2020.
doi:10.3324/haematol.2020.248518
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/7/1780
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