Leukoencephalopathy During Daratumumab-Based Therapy: A Case Series of Two Patients with Multiple Myeloma

Abstract

Syeda Saba Kareem,1 Neena Viswanathan,2 Solmaz Sahebjam,2 Nam D Tran,2 Tyra Gatewood,2 Katherine Tobon,1 Rachid Baz,1 Yolanda Piña,2 Kenneth H Shain,1,3 Sepideh Mokhtari2 1Malignant Hematology Department, Moffitt Cancer Center, Tampa, FL, USA; 2Neuro-Oncology Department, Moffitt Cancer Center, Tampa, FL, USA; 3Tumor Biology Department, Moffitt Cancer Center, Tampa, FL, USACorrespondence: Syeda Saba Kareem, Malignant Hematology Department, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL, 33612, Tel [phone], Fax [phone], Email [email protected]: Leukoencephalopathy in the setting of multiple myeloma (MM) is a rare demyelinating condition, with few reported cases in literature. Daratumumab is a CD38 targeted monoclonal antibody that has been widely used for the management of MM. In the absence of central nervous system (CNS) disease, many medication-induced leukoencephalopathy cases reported with MM, including daratumumab-induced, are associated with progressive multifocal leukoencephalopathy (PML) and John Cunningham (JC) virus. Currently, there are no reported cases of daratumumab-induced leukoencephalopathy among patients without CNS involvement or PML. We discuss 2 patients who developed leukoencephalopathy while receiving daratumumab-based therapy without evidence of PML or CNS disease. Both patients had baseline MRIs without significant white matter changes before daratumumab-based therapy. Patients began experiencing neurological deficits about 6 to 8 months after daratumumab-based therapy initiation. One patient passed away before being assessed for improvement of symptoms with daratumumab cessation. The second patient had some stabilization of symptoms after cessation; however, the leukoencephalopathy remained irreversible. As the class of anti-CD38 monoclonal antibodies expands in MM therapy, we highlight a potential treatment complication and the importance of detecting leukoencephalopathy early among patients receiving anti-CD38 therapy. We recommend vigilant monitoring of any new or worsening neurological symptoms to avoid serious complications of irreversible leukoencephalopathy.Keywords: anti-CD38, monoclonal antibody, neurotoxicity, plasma cell disorder, white matter changes, daratumumab, leukoencephalopathy, case report

Keywords

• anti-cd38
• monoclonal antibody
• neurotoxicity
• plasma cell disorder
• white matter changes
• daratumumab
• leukoencephalopathy
• case report