Central nervous system involvement by multiple myeloma: A multi‐institutional retrospective study of 172 patients in daily clinical practice

Abstract

The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of patients with multiple myeloma (MM) involving the central nervous system (CNS). Univariate and multivariate analyses were performed to identify prognostic factors for survival. The median time from MM diagnosis to CNS MM diagnosis was 3 years. Thirty-eight patients (22%) were diagnosed with CNS involvement at the time of initial MM diagnosis and 134 (78%) at relapse/progression. Upon diagnosis of CNS MM, 97% patients received initial therapy for CNS disease, of which 76% received systemic therapy, 36% radiotherapy and 32% intrathecal therapy. After a median follow-up of 3.5 years, the median overall survival (OS) from the onset of CNS involvement for the entire group was 7 months. Untreated and treated patients had median OS of 2 and 8 months, respectively (p<0.001). At least one previous line of therapy for MM before the diagnosis of CNS disease and >1 cytogenetic abnormality detected by FISH were independently associated with worse OS. The median OS for patients with 0, 1 and 2 of these risk factors were 25 months, 5.5 months and 2 months, respectively (p<0.001). Neurological manifestations, not considered chemotherapy-related, observed at any time after initial diagnosis of MM should raise a suspicion of CNS involvement. Although prognosis is generally poor, the survival of previously untreated patients and patients with favorable cytogenetic profile might be prolonged due to systemic treatment and/or radiotherapy.

Leptomeningeal Myelomatosis: A Rare but Devastating Manifestation of Multiple Myeloma Diagnosed Using Cytology, Flow Cytometry, and Fluorescent in situ Hybridization

“…Our data indicate that, in LMM, the median survival is also < 3 months. This is in line with 2 larger series that recently reported on the outcome of patients with CNS involvement of MM [6,7]. Paludo et al [6] found an incidence of for myelomatous involvement in 0.7% of a large cohort of > 4,000 patients diagnosed and treated at the Mayo Clinic; in this group of 29 patients, the median overall survival was only 3.4 months.…”

“…There was no specific therapeutic intervention identified that could positively influence the natural cause of the disease. In a multi-institutional study reported by Jurczyszyn et al [7], the median overall survival for the entire group of 172 patients was 7 months from the onset of CNS involvement. However, when they included the presence of > 1 cytogenetic abnormality detected by FISH and at least 1 prior therapy, the median survival of this group of patients was only 2 months.…”

“…Only a few comprehensive overviews with > 10 patients have been published [1][2][3][4][5][6][7]. LMM is defined as the presence of clonal plasma cells in the cerebrospinal fluid DOI: 10.1159/000489484 (CSF).…”

Multiple myeloma with clivus involvement, neurological symptoms, and 45 g/L proteinorachia

“…It is associated with poor prognosis, life expectancy in this case being 4‐6 months, thus requires rapid clinical intervention. The standard criterion for the diagnosis of CNS MM is based on cytology, which lacks sensitivity . Here we describe a patient with impairment of consciousness with a huge hyperproteinorachia but no signs of meningitis.…”

Case Study of Intracerebral Recurrence of Plasmablastic Myeloma with Achievement of Complete Response after Treatment with Lenalidomide

“…1 Involvement of central nervous system (CNS) is observed in less than 1% of all MM patients 2,3 and is diagnosed either by presence of neoplastic plasma cells in CSF 4 or evidence of intraparenchymal or meningeal involvement as detected by MRI. The largest study was performed in Mayo Clinic and included over 4000 MM patients observed over 16-year period.…”