An infusion of autologous T cells transduced with an anti–CD19 chimeric antigen receptor led to a complete response in a patient with refractory multiple myeloma, according to a case report published in The New England Journal of Medicine.
The patient — a woman diagnosed with multiple myeloma in 2009 when aged 43 years — initially responded to treatment with lenalidomide (Revlimid, Celgene), bortezomib (Velcade; Takeda, Millennium) and dexamethasone, but experienced progression after a brief therapy cessation.
An autologous stem cell transplantation — followed by myeloablative chemotherapy with 200 mg/m2 melphalan — produced a brief partial response.
Alfred L. Garfall, MD, assistant professor of medicine at the Hospital of the University of Pennsylvania, and colleagues sought to determine whether autologous stem cell transplantation treatment with autologous T cells transduced with a CD19-directed chimeric antigen receptor (CTL019) could produce a complete response in the patient.
The patient underwent transplantation after receiving 140 mg/m2 melphalan. Transplant-related adverse events that the patient experienced included grade 4 neutropenia and thrombocytopenia, grade 3 mucositis, grade 2 nausea and anorexia, neutropenic fever and Staphylococcus aureus bacteremia.
The patient underwent CTL019 infusion 12 days after transplantation, at a dose of 5 x 107. The researchers observed no fevers or signs of cytokine release syndrome after infusion.
No adverse events related to CTL019 occurred. Further, all transplantation-related adverse events resolved by day 100 after the procedure.
The patient began a treatment regimen of 5 mg daily lenalidomide beginning day 130 after transplantation. The researchers subsequently reduced the dose to 5 mg twice weekly due to gastrointestinal adverse events.
The patient achieved a complete response — with no evidence of progression and no measurable serum or urine monoclonal protein at 12 months — despite the absence of CD19 expression in 99.95% of her neoplastic plasma cells.
“Ten patients, including the patient described in detail here, have been treated so far in this trial,” Garfall and colleagues wrote. “Six of the 10 patients remain progression-free. The only additional CTL019-attributable adverse events observed have been one instance of grade 1 cytokine release syndrome and one instance of grade 3 enterocolitis due to autologous graft-versus-host disease.” – by Cameron Kelsall
Disclosure: Novartis provided funding for this study. Garfall reports grants from Novartis and the NIH/NCI during the conduct of the study. Please see the full study for a list of all other researchers’ relevant financial disclosures.