93 percent of refractory leukemia patients in remission after CAR-T cell treatment

Researchers reported that 27 out of 29 patients with advanced refractory leukemia went into remission after receiving their own genetically-modified immune cells made with a specific ratio of chimeric antigen receptor (CAR) T cells, according to a study published online April 25, 2016 in the Journal of Clinical Investigation.

Other studies have also shown remission of cancer using CAR-T cells to target the CD19 molecule, which is a biomarker of B cell tumors.

But this is the first clinical trial in which patients were given CD19-specific CAR-T cells that were formulated with an even ratio of human CD4⁺ helper and CD8⁺ killer T cells, which worked together to eliminate cancer in 93% of patients with B cell acute lymphoblastic leukemia.

“You don’t expect results like these from early-phase trials,” said senior author David Maloney, MD, PhD, of the Clinical Research Division at Fred Hutchinson Cancer Research Center, in Seattle, WA. “In early-phase trials, you’re continually learning. That’s why these response rates are so extraordinary.”

In preclinical studies, the researchers discovered that an infusion that combined CD8⁺ CAR-T cells and CD4⁺ CAR-T cells in a 1 to 1 ratio might provide the best efficacy.

In this study, the scientists collected blood cells from each patient, then divided each patient’s blood into two equal portions—one half was enriched with CD4⁺ T-cells and the other half with CD8⁺ T cells. After further development into a CD19-targeted CAR-T cell product, it was infused by IV into the patients.

At 3 weeks after infusion, all patients had no detectable leukemia by bone marrow testing. In 27 of 29 patients, no detectable leukemia was found by high-resolution flow cytometry.

“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 study leader Cameron Turtle, MBBS, PhD, a hematology oncologist in the Clinical Research Division at Fred Hutchinson.

Of the 2 participants who didn’t go into complete remission, 1 eventually re-enrolled in the trial and went into complete remission after receiving a higher dose of CAR-T cells.

However, not all patients remained in complete remission. At least 4 relapsed and were treated again with CAR-T cells; of these, 2 relapsed with leukemias that were immune to the CAR-T cells.

It’s too early to know what the long-term outcomes of this therapy will be, the researchers acknowledged.

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