Chimeric antigen receptor T cell therapy shows promise for precision immunotherapy in relapsed/refractory multiple myeloma
A chimeric antigen receptor (CAR) construct designated LCAR-B38M CAR T that targets principally B cell maturation antigen (BCMA) has shown potential as an innovative and effective treatment for multiple myeloma, according to a new poster presentation from the American Society of Clinical Oncology (ASCO) Annual Meeting.1 A 100% objective response rate to LCAR-B38M CAR-T cells was observed in refractory/relapsed multiple myeloma patients. In total, 18 out of 19 (95%) patients reached complete remission (CR) or near CR status without a single event of relapse in a median follow-up of 6 months.
The major adverse event associated with CAR T cell therapy is cytokine release syndrome (CRS). This is linked with fever, low blood pressure and breathing difficulty, and can be life threatening. The majority (14/19) of the patients experienced this syndrome although it was generally mild and transient.
“The majority of myeloma patients are going to express BCMA,” said researcher, Noopur Raje, MD of Massachusetts General Hospital Cancer Center in Boston.
“Because the antigen is not widely expressed T cells targeting BCMA are less likely to cause adverse events” commented Sagar Lonial, MD, from Emory University in Atlanta.
In another study, sponsored by bluebird bio, also presented at the ASCO Annual Meeting, updated efficacy and safety results were reported for bb2121 anti-BCMA CAR T cell therapy.2 Testing a range of doses, researchers found that when patients received more than 150 million cells, the overall response rate of the six patients with evaluable data at these doses was 100%. As of the data cut-off, which was on November 18, 2016, no Grade 3 or higher neurotoxicities or CRS had been observed. Grade 1–2 CRS had been reported in 73% (8/11) treated patients.
Clinical development and manufacture of chimeric antigen receptor T cells have recently been reviewed by Drs Andrew Fesnak and Una O’Doherty, in the current issue of European Oncology & Haematology.3
1. Fan F, Zhao W, Liu J, et al., Durable remissions with BCMA-specific chimeric antigen receptor (CAR)-modified T cells in patients with refractory/relapsed multiple myeloma, J Clin Oncol, 2017;35:Abstract LBA3001.
2. Berdeja J, Lin Y, Raje NS, et al., First-in-human multicenter study of bb2121 anti-BCMA CAR T-cell therapy for relapsed/refractory multiple myeloma: Updated result, J Clin Oncol, 2017;35:(suppl; abstr 3010)
3. Fesnak A, O’Doherty, U, Clinical Development and Manufacture of Chimeric Antigen Receptor T cells and the Role of Leukapheresis, European Oncology & Haematology, 2017;13:Epub ahead of print.