Clinical Characteristics and Prognosis of Central Nervous System Involvement in Multiple Myeloma: A Multicenter Retrospective Analysis from China
Authors: Li Wenjing , Tian Weiwei , Ma Jie , Li Linyu , Li Zhihua , Gao Guorong , Zhang Lan , Duan Lixiang , Geng Hui , Meng Jie , Gao Wen 
Published: December 2024

Background: Central nervous system (CNS) involvement is a rare extramedullary complication of multiple myeloma (MM-CNS), which occurs at an extremely low incidence but usually leads to dismal clinical outcomes. There were few studies on the clinical characteristics and prognosis of MM-CNS. We summarize the characteristics of MM-CNS cases from China.

Methods: We conducted a retrospective analysis of MM-CNS cases from nine centers in China during the period from July 1, 2017, to June 30, 2024, in order to analyze their clinical characteristics, treatment approaches and prognosis.

Results: Over 7-year period, 35 MM-CNS cases were admitted to 9 centers in China, including 16 males and 19 females. The median age at the diagnosis of CNS involvement was 55 years (range, 40-83 years). 11 (31.4%) cases had CNS involvement at diagnosis and it occurred to 24 (68.6%) after treatment. For patients who developed CNS involvement with progression, the number of lines for anti-myeloma therapy was 2 (range, 1-8), and the median time from the diagnosis of MM to CNS involvement was 22.8 months (range, 2.4~77.7). Regarding M proteins type, 18 (51.4%) cases had IgG, 11 (31.4%) IgA, 4 (11.4%) IgD, and 2 (5.7%) light chain. There were 9 (25.7%) cases with soft tissue plasmacytoma, 3 (8.6%) cases with pleural involvement, and 1 (2.9%) case with plasma cell leukemia. Chromosomal fluorescence in situ hybridization (FISH) was performed in 29 patients. 1q21 amplification was found in 14 (48.3%) cases, 17p deletion in 3 (10.3%) , t(11;14) in 1 (3.4%) , t(4;14) in 4 (13.8%) , and t(14;16) in 1 (3.4%) respectively. Chromosomal karyotyping was done in 14 cases, and complex karyotypes were identified in 5 (35.7%) cases.

Two cases were diagnosed by means of histopathology, 18 cerebrospinal fluid, and the others 15 imaging examination respectively. Imaging abnormalities were identified in 24 cases, including 6 with meningeal involvement alone, 16 with parenchymal involvement alone and 2 with both meningeal and parenchymal involvement. Cerebrospinal fluid examinations were conducted for 18. Among them, protein was elevated in 12/18 (66.7%), abnormal plasma cells were observed by morphology in 11/18 (61.1%), and abnormal plasma cells were identified by flow cytometry in 10/12 (55.6%). Compared with cases with CNS involvement at diagnosis, cases with CNS involvement after treatment had a higher proportion of meningeal involvement (53.3% vs. 0%, p=0.007) and cerebrospinal fluid abnormalities (83.3% vs. 33.3%, p= 0.03).

Among 35 patients, 2 received no treatment, and 33 cases were treated with combination therapy (30 cases) or intrathecal injection alone (3 cases). There were 30 cases with chemotherapy (9 cases proteasome inhibitors (PI)-based regimens, 3 cases immunomodulatory drugs (IMiDs)-based regimens, 2 cases PI+IMiDs-based regimens, and 7 cases daratumumab-based regimens), 13 cases intrathecal injection，and 6 cases radiotherapy respectively. In addition, 4 cases were consolidated with autologous stem cell transplantation (ASCT) as first line therapy and 4 cases with CAR-T therapy as salvage. 8 cases achieve no response after treatment, and the remaining 25 cases had varying degrees of response. Among them, 5 cases were in complete remission after treatment, 10 cases showed improvement in both imaging and cerebrospinal fluid, 8 cases had improvement only in cerebrospinal fluid, and 2 cases had improvement in symptoms. Of the 25 patients in response after treatment, 14 patients experienced relapsed disease within median 3.1 months.

The median follow up was 19.1 months (ranging, 0.1-46.8). At the end of the follow up, 21 patients died, with a median overall survival (OS) of 13.0 months (range, 0.1-43.1). Survival analysis showed that cases with CNS involvement at diagnosis had longer OS than that with CNS involvement after treatment (34.0 vs. 12.8 months, p=0.01). Only 3 patients had long survival with 34.5, 42.2, and 43.1 months for OS respectively. All the 3 cases were found to have localized involvement of brain parenchyma as clinical manifestations and then they were diagnosed as MM. They achieved complete remission after surgical resection followed by chemotherapy plus ASCT.

Conclusions: MM-CNS is a rare and rapidly progressive clinical condition. Although treatment with novel agents may temporarily improve clinical symptoms, most patients have very short OS. More effective regimens need to be developed in future.