Response to T-cell Immunotherapy Promising for Patients With Advanced B-cell Acute Lymphocytic Leukemia

Response to T-cell Immunotherapy Promising for Patients With Advanced B-cell Acute Lymphocytic Leukemia
Response to T-cell Immunotherapy Promising for Patients With Advanced B-cell Acute Lymphocytic Leukemia

Remission was achieved for 27 of 29 patients with advanced B cell acute lymphocytic leukemia (ALL) in an early phase trial of CAR T cells. These patients, whose advanced leukemia had been resistant to multiple other forms of therapy, were treated with genetically engineered T cells.1

"Patients who come onto the trial have really limited options for treatment. They have refractory, acute leukemia. So the fact that we're getting so many into remission is giving these people a way forward," said Cameron Turtle, MD, of the Fred Hutchinson Cancer Center in Seattle, Washington, and study leader.

The immune system does not always eliminate cancer cells, which often evade it. This experimental therapy genetically engineered patients' T cells with a synthetic receptor molecule called a CAR (chimeric antigen receptor) that empowers the T cells to recognize and kill cancer cells that bear a specific marker, CD19.

The phase 1/2 clinical trial sought to evaluate the safety of administering the engineered cells and to lay plans for future improvements. T cells were extracted from 29 patients and a specialized virus was used to grow CARs inside the cells, multiplying to the billions. The patients underwent chemotherapy before the reengineered cells were infused back into the patients they came from.

This study used an even mixture of helper (CD4+) and killer (CD8+) T cells, which work together to kill cancer cells. This is the first study to infuse patients with a defined ratio of killer and helper T cells. The well-controlled method allowed the authors to provide the first clear evidence of the relationships between the doses of cells participants received and their outcomes after infusion.

A few weeks after the infusion, 27/29 patients (93%) achieved bone marrow remission, measured by flow cytometry. Of the 2 participants who did not go into complete remission, 1 eventually reenrolled in the trial and went into complete remission after receiving a higher dose of cells.

"This is just the beginning," Turtle said. "It sounds fantastic to say that we get over 90% remissions, but there's so much more work to do to make sure they're durable remissions, to work out who's going to benefit the most, and extend this work to other diseases."

Reference

1. Turtle CJ, Hanafi LA, Berger C, et al. CD19 CAR–T cells of defined CD4 :CD8 composition in adult B cell ALL patients [published online ahead of print April 25, 2016]. J Clin Invest. doi:10.1172/JCI85309.

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