Outcome of Patients with Central Nervous System Multiple Myeloma (CNS-MM) Treated with CNS-Directed Radiation Therapy

Abstract

<h3>Purpose/Objective(s)</h3> Extramedullary spread of multiple myeloma into the central nervous system (CNS-MM) is rare and confers a poor prognosis, with reported overall survival (OS) of 2-7 months. Outside of case reports, there is an undefined role of CNS-directed radiation therapy (RT) in managing CNS-MM. Here, we report our institutional outcomes in a cohort of patients with CNS-MM treated with CNS-directed RT. <h3>Materials/Methods</h3> We retrospectively identified patients with CNS-MM (established by CSF cytology, flow cytometry, or MRI brain/spine), treated with CNS-directed RT from 2015-2020. CNS-MM was defined as having leptomeningeal disease (LMD), parenchymal disease, or CSF involvement. Complete response (CR) was defined as having no cells in CSF or resolution of radiographic disease on MRI. Otherwise, patients were recorded as having partial response (PR) or stable disease (SD). The Kaplan-Meier method was used to estimate OS. <h3>Results</h3> Sixteen patients met inclusion criteria. CNS-MM was confirmed in 11 patients (69%) by CSF and MRI, 3 patients (19%) by CSF alone, and 2 patients (12%) by MRI alone. At CNS-MM diagnosis, 7 patients (43.8%) had received ≥3 prior lines of therapy, 7 (43.8%) were in 1^st/2^nd relapse, and 2 were newly diagnosed. The median time to CNS-MM from initial MM diagnosis was 40.3 mos (range: 0-105). Nine patients (56.3%) had high-risk disease as defined by plasmablastic morphology, cytogenetic features, or LDH elevation. Time to RT from CNS-MM diagnosis was 27 days (range: 9-264). Ten patients (62.5%) underwent craniospinal irradiation (CSI), four (25%) received brain RT (3 focal, 1 whole brain), and 2 (12.5%) received spine RT. The median dose was 23.4 Gy (3.6-30 Gy) in 12 fractions (2-15). Eight patients (50%) also received intrathecal therapy with cytarabine following CNS-MM diagnosis. Two patients (12.5%) underwent SCT post-RT. For the entire cohort (n=16), median OS was 46.6 mos (range: 11-125) from MM diagnosis, 4.2 mos (0.7-60.6) post-diagnosis of CNS-MM, and 3.9 mos (0.43-52) from start of RT. Fifteen patients completed the intended RT and 9 patients (60%) were evaluable post-RT with adequate follow-up consisting of CSF analysis and/or MRI imaging. For the 9 evaluable patients, the median OS from the start of RT was 7.23 mos (range: 3.1-52.1), with CR following RT in 6 patients (66.7%), PR in 2 patients (22.2%) by imaging, and SD in 1 patient (11.1%) by imaging and CSF cytology. Among the 6 patients that completely responded to RT, local relapse occurred in 2 patients at 3 mos and 1 patient at 24 mos post-RT. For the 6 patients with CR after RT, the median OS was 7.27 mos (3.2-52.1) from the start of RT, and 9.2 mos (3.8-60.6) from CNS-MM diagnosis. <h3>Conclusion</h3> Multiple myeloma patients with CNS involvement represent a high-risk patient population. Aggressive multimodality therapy may induce durable CNS control in a small subset of patients. CNS-directed RT may be an effective treatment strategy in selected patients and may increasingly be important to consider in the era of CAR T-cell therapy.