Authors: Jade Parker
A study published recently in Science Translational Medicine, conducted by a group of researchers from the Fred Hutchinson Cancer Research Center (WA, USA), has demonstrated promising results for a chimeric antigen receptor (CAR)-T cell treatment in combination with cyclophosphamide (Cy)-based lymphodepletion in advanced non-Hodgkin lymphoma (NHL) patients.
Factors affecting toxicity and efficacy still elude researchers, due to variations in both lymphodepletion and the heterogeneity of CAR-T cells administered to individual patients. In this early phase, dose-finding study researchers demonstrated that administering Cy-based lymphodepletion chemotherapy in combination with fludarabine increased the expansion and persistence of CAR-T cells.
NHL patients who received CAR-T cells following Cy/fludarabine -based lymphodepletion demonstrated promising early efficacy and side effect profiles, with many experiencing improved overall response, complete remission and progression-free survival rates compared with those NHL patients who received Cy-based lymphodepletion without fludarabine.
Study leader Cameron Turtle (Fred Hutchinson Cancer Research Center) commented: “This study shows that at the right dose of CAR-T cells and lymphodepletion, we can achieve very good response rates for NHL patients who have no other treatment options.”
Overall, the researchers believe that their work highlights the feasibility of CAR-T cell therapy for advanced NHL patients and the importance of selecting the correct dose of the cells. The authors acknowledged that the optimal T-cell dose is still unknown and this, in addition to toxicity profiles, need to be studied further.
C J Turtle, LA Hanafi, C Berger et al. Immunotherapy of non-Hodgkins lymphoma with a defined ratio of CD8 and CD4 CD19-specific chimeric antigen receptor-modified T cells. Sci. Transl. Med.; 8 (355): 355ra116 (2016) DOI: 10.1126/scitranslmed.aaf8621; Fred Hutchinson Cancer Center press release: JCAR014 clinical data published in Science Translational Medicine: Patients with advanced lymphoma in remission after T-cell therapy