Patterns of CNS Involvement in Relapsed and/or Refractory Multiple Myeloma.
Authors: Abdallah Al-Ola , Atrash Shebli , Muzaffar Jameel , Ahmad Nisar , Haider Sajjad , Grazziutti Monica , Apewokin Senu , Shahid Zainab , Restrepo Alejandro , Waheed Sarah , van Rhee Frits , Barlogie Bart , Usmani Saad Z 
Published: October 2019

Abstract
Abstract 2925

Background:
Multiple myeloma (MM) patients can present with neurologic manifestation either as part of the disease process or as a therapeutic complication, such as due to metabolic disorders such as hypercalcemia, uremia and hyperviscosity; due to peripheral neuropathy, spinal cord compression and cranial nerve infiltration. Invasion of the central nervous system (CNS) in MM disease is an extremely rare occurrence and is associated with advanced disease with poor prognosis. Herein, we are presenting the UARK experience of CNS involvement in MM.

Patients and Methods:
The UARK MM database was used to conduct a retrospective analysis identifying CNS MM cases presenting between January 1996 and March 2012. Cases were identified from a review of the cytology laboratory archive material; data were also retrieved from the cytogenetic laboratory database, and magnetic resonance imaging (MRI). Descriptive analyses were performed on available data on patient characteristics, disease course and outcomes.

Results:
35 patients were identified with mean age at diagnosis being 55.4 years (range: 32–80 years) presenting with neurologic symptoms enlisted in Table 1. All patients had received prior systemic chemotherapy (SC) alone (n=11), or combination of SC and autologous stem cell transplant (ASCT, n=21), or combination of ASCT and allogeneic stem cell transplant (n=3). Eight (23.5%) patients had elevated B2M >5.5 mg/L, twenty four (71%) patients had elevated LDH (> 2 times upper limit of normal) and 5 (14%) had secondary plasma cell leukemia. The mean interval from diagnosis of MM to diagnosis of CNS MM was 23.5 months (range: 3–121 months). At the time of diagnosis of CNS MM, 3 (8.6%) patients were in complete remission (CR) by standard criteria and 15 (42.9%) patients were in progressive disease (PD). Magnetic resonance imaging (MRI) was performed in 34 patients, showing diffuse or localized leptomeningeal disease in 20 (58.8%) patients, 3 (8.8%) patients had a combination of both leptomeningeal disease with adjacent breakout MM focal lesion, and 2 (6%) patients had MM focal lesions adjacent to the meninges and sinuses without leptomeningeal disease. All 35 patients had malignant plasma cells in CSF analysis. 31 patients received chemotherapy to include intrathecal chemotherapy (IT) as a part of their treatment. IT consisted of cytarabine, methotrexate and hydrocortisone +/− thiotepa. 28 patients were treated with both IT and SC together: alone (n=8), or in combination of ASCT (n=13), or combination of ASCT and cranial irradiation (CI) (n=4), or combination with CI (n=1), or combination with both CI and Allogeneic SCT (n=1), or with Allogeneic SCT (n=1).

Conclusion:
In our experience, CNS MM is an aggressive terminal disease feature associated with other poor prognostic disease features such as high B2M, LDH and secondary plasma cell leukemia. The present review suggests that the patterns for CNS involvement are variable, such as hematogenous spread of plasma cells seen in PCL, or direct continuous spread from the eroded lytic lesions of the skull. The available novel agents do not provide therapeutic concentrations of drug in the CSF as they do not cross the blood-brain barrier. The study highlights an unmet need in this subset of high risk, relapsed/refractory MM patients. Adequate CNS penetration needs to be considered in MM novel drug development.

Disclosures:
No relevant conflicts of interest to declare.