Therapies Using Immune Engineering Show Promise for Acute Lymphoblastic Leukemia (ALL)

(Clinical Oncology News) – Two strategies that involve immune engineering have produced highly encouraging responses in acute lymphoblastic leukemia (ALL), according to data from separate studies presented at the 2014 annual meeting of the American Society of Hematology (ASH).

In one study, T cells engineered for chimeric antigen receptor (CAR) targeting were used in children with relapsed or refractory disease. In the other, a bispecific monoclonal antibody was used to achieve negative minimal residual disease (MRD) status in adult ALL patients already in hematologic complete remission (CR). The results of both trials were positive and both strategies appear poised for accelerated development, investigators said.

In the pediatric study, 36 of 39 children achieved a CR after an induction infusion of modified T cells (abstract 380). Although 10 of the responders have relapsed, 26 of the remissions persisted, with a median follow-up of six months and maximum follow-up of 31 months. No relapse occurred in any patient who remained in remission 12 months after the infusion.

The T cells were engineered with a CD19-directed CAR (CTL019, Novartis), which the FDA has given a breakthrough therapy designation. In all responders, these infused cells, called CTL019, have produced CD19+ B-cell aplasia, according to the principal investigator Stephan Grupp, MD, PhD, the director of Translational Research at Children’s Hospital of Philadelphia’s Center for Cancer Research. Early and robust proliferation of CTL019 cells correlated with response. Persistent B-cell aplasia in long-term responders suggests that the CTL019 cells, which are administered one week after lymphodepleting chemotherapy, may remain functional even after they are no longer detectable with flow cytometry, according to Dr. Grupp.

 

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