CD19 CAR T-Cell Therapy Effective for Relapsed/Refractory DLBCL

December 20, 2017

CAR T cells targeting CD19 can be effective at treating relapsed/refractory diffuse large B-cell lymphoma or follicular lymphoma, with high rates of durable remission.

Chimeric antigen receptor (CAR) T cells targeting CD19 can be effective at treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma, with high rates of durable remission observed in a small study of patients. The results of this study were published in the New England Journal of Medicine.

“Our observed complete response rates of 43% for patients with DLBCL and 71% for those with follicular lymphoma, with sustained remissions lasting up to 3 years after a single dose of CTL019 cells, support further development of this approach,” wrote Stephen J. Schuster, MD, of the University of Pennsylvania’s Abramson Cancer Center, and colleagues.

According to the study, only about half of patients with relapsed or refractory DLBCL are candidates for treatment with high-dose chemotherapy with autologous stem cell transplantation, and even among those treated with this approach, the 3-year event-free survival rate is only about 20%. Similarly, patients with follicular lymphoma with early relapse have poor survival.

“Adoptive immunotherapy that incorporates T cells that have been genetically engineered to express a CAR for the pan–B-cell CD19 antigen has been associated with high response rates in patients with relapsed or refractory B-cell cancers, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, and B-cell non-Hodgkin lymphoma,” Schuster and colleagues wrote.

In this study, they tested autologous T cells that express a CD19-directed CAR to treat patients with DLBCL or follicular lymphoma who had relapsed or were refractory to prior treatments.

The study included 28 adults who received CTL019 cells; more than half responded (64%). Six of 14 patients with DLBCL (43%) and 10 of 14 patients with follicular lymphoma (71%) achieved complete remission.

According to the researchers, CTL019 cells proliferated and were detectable in the blood and bone marrow of both responders and nonresponders.

Certain patients were able to achieve sustained responses to treatment. With a median follow-up of 28.6 months, 86% of patients with DLBCL and 89% of patients with follicular lymphoma who had a response maintained the response.

Additionally, all patients who were in complete remission by 6 months remained in remission at 7.7 to 37.9 months after induction. There was sustained reappearance of B cells in 8 of 16 patients and improvement in levels of IgG and IgM, as well as IgA

Five patients in the trial had severe cytokine release syndrome. One patient was treated with tocilizumab, had a rapid reversal, and was able to achieve a complete response. No deaths from cytokine release syndrome occurred.