Anti-CD19 Chimeric Antigen Receptor T-Cell Treatment Produces Response in Patient With Refractory Multiple Myeloma
As reported by Garfall et al in The New England Journal of Medicine, a patient with refractory multiple myeloma who had undergone prior autologous stem cell transplantation and multiple lines of therapy exhibited a complete response to a second autologous transplantation followed by infusion of anti-CD19 chimeric antigen receptor T (CTL019) cells. The response was observed despite the absence of CD19 expression in neoplastic cells.
Treatment History
After initial diagnosis, the patient had a response to lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone but had progressive disease when treatment was stopped to collect hematopoietic stem cells for autologous transplantation; the patient then received infusion of cisplatin, doxorubicin, cyclophosphamide, and etoposide. Treatment with high-dose melphalan at 200 mg/m2 and autologous transplantation resulted in a partial, transient response. Subsequent treatment included regimens containing lenalidomide, bortezomib, carfilzomib (Kyprolis), pomalidomide (Pomalyst), vorinostat (Zolinza), clarithromycin, and elotuzumab.
CTL019 Treatment
Approximately 4 years after initial treatment and after having received nine lines of therapy, the patient enrolled in a clinical trial of CTL019 cells and autologous transplantation. Cyclophosphamide was given in two cycles at 1,200 mg/m2 over 96 hours during production of the CTL019 cells. The patient underwent autologous transplantation after receiving melphalan 140 mg/m2. The CTL019 infusion, consisting of 5×107 chimeric antigen receptor-expressing T cells, was given at 12 days after transplantation.
The patient exhibited a complete response, with no evidence of progression and no detectable serum or urine monoclonal protein at the most recent evaluation at 12 months after treatment. The response was achieved despite the absence of CD19 expression in 99.95% of neoplastic plasma cells.
The investigators concluded: “[W]e report a case of advanced, refractory multiple myeloma in which a durable complete response has been attained with CTL019 infusion after treatment with high-dose melphalan and autologous transplantation, despite the absence of CD19 expression in the vast majority of neoplastic cells.” They noted: “The superior reduction in disease burden and durability of this response in comparison with the response to the previous transplantation, despite the extensive intervening therapy and lower dose of melphalan, suggest that the favorable response is attributable to the combination of CTL019 and melphalan rather than melphalan alone.”
Carl H. June, MD, of the University of Pennsylvania, is the corresponding author of The New England Journal of Medicine article. Alfred L. Garfall, MD, and Marcela V. Maus, MD, PhD, of Perelman School of Medicine, University of Pennsylvania, contributed equally to The New England Journal of Medicine article.
The study was funded by Novartis and others. For full disclosures of the study authors, visit www.nejm.org.
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