Posterior Reversible Encephalopathy Syndrome (PRES) after Infusion of Anti-Bcma CAR T Cells (CART-BCMA) for Multiple Myeloma: Successful Treatment with Cyclophosphamide

• Published in: Blood 2016-12, Vol.128 (22), p.5702-5702
• Main Authors: Garfall, Alfred L., Lancaster, Eric, Stadtmauer, Edward A, Lacey, Simon F., Dengel, Karen, Ambrose, David E, Chen, Fang, Gupta, Minnal, Kulikovskaya, Irina, Vogl, Dan T., Plesa, Gabriela, Weiss, Brendan M, Ferthio, Regina, Richardson, Celeste, Melenhorst, Jan Joseph, Levine, Bruce L, June, Carl H, Milone, Michael, Cohen, Adam D.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V128.22.5702.5702

Neurologic toxicity has been observed with anti-CD19 chimeric antigen receptor (CAR) T cells and the anti-CD19 BiTE blinatumomab. Both focal (e.g., cranial nerve palsy) and global (e.g., generalized seizures) abnormalities have been reported, often associated with systemic cytokine release syndrome (CRS) but also observed after recovery from or in absence of CRS. CART-BCMA consists of expanded autologous T cells transduced with a 4-1BB:CD3-zeta-based CAR specific for B Cell Maturation Antigen. Here, we report clinical features and management of a severe neurotoxicity observed on a phase 1 trial of CART-BCMA for multiple myeloma (MM) (NCT02546167). The subject is a 55-year-old female with high-risk IgA lambda MM. At time of CART-BCMA infusion, her MM manifestations included cytopenias and plasmacytomas of the pleura and paravertebral muscles. Bone marrow (BM) was >95% BCMA+ plasma cells. Pre-treatment brain MRI showed pachymeningeal thickening and enhancement over the left cerebral convexity, possibly due to extension of calvarial MM lesions. There was no evidence of CNS MM on a neurologist’s exam or by CSF cytology. The subject received 2x108 CART-BCMA cells, 40% of the planned dose, over two consecutive days, without lymphodepleting chemotherapy; a third planned infusion was held due to fevers. Over the next 4 days, fevers persisted, hypoxia and delirium developed, and cytopenias worsened. Brain MRI and lumbar puncture on day 4 showed no new abnormalities. Evaluation for infection was negative. These symptoms coincided with rise in serum IL-6 (nl range