CD22-Targeted CAR T-Cell Therapy Active for Relapsed/Refractory ALL

December 5, 2016

T-cell therapy targeting CD22, a protein found on the surface of leukemic cells, was safe and feasible in a small and ongoing study of patients with ALL.

T-cell therapy targeting CD22, a protein found on the surface of leukemic cells, was safe and feasible in a small and ongoing study of patients with acute lymphoblastic leukemia (ALL), according to the results of a phase I dose-escalation study (abstract 650) presented at the American Society of Hematology (ASH) 58th Annual Meeting and Exposition, held December 3–6 in San Diego, California.

The study was the first to evaluate chimeric antigen receptor (CAR) targeting CD22 in humans.

“This is the first successful salvage CAR therapy for CD19-negative B-ALL,” said Terry J. Fry, MD, of the Center for Cancer Research at the National Cancer Institute in Bethesda, Maryland.

Previously, researchers have had success with CAR therapy targeting CD19 in patients with relapsed or refractory ALL.

“We are learning now that one of the limitations of this approach is loss of CD19 expression occurring in potentially a substantial number of patients,” Fry explained. “CD22 is a well-defined alternative target.”

This phase I study was open to children and young adults with relapsed/refractory CD22-positive hematologic malignancies. All patients underwent autologous leukopheresis for peripheral blood mononuclear cells. Cells were then enriched and cultured in the presence of anti-CD33/CD28 beads followed by lentiviral vector supernatant containing the anti-CD22 CAR, with culture duration of 7 to 10 days. Patients began lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by cell infusion.

Fry presented results from the first 16 patients on the study. All patients had previously undergone at least one prior allogeneic stem cell transplant. Eleven patients had received prior CD19-targeting therapy, and nine patients were CD19-negative or had reduced expression of CD19.

The researchers tested three dose levels: 3 x 105, 1 x 106, and 3 x 106. Dose level 2, 1 x 106, is the dose used in most CD19 CAR trials, according to Fry. Dose level 2 was chosen as the biologically active dose.

Looking at patients treated at dose level 2 or higher, the complete remission rate was 80%. These patients had no evidence of residual disease after 1 month of their infusion. One additional patient treated at a lower dose also achieved remission. The researchers have observed several sustained remissions, with 1 patient in remission for longer than 1 year, 1 patient in remission for 6 months, and 1 patient in remission for 3 months. However, 6 of 9 patients who achieved remission have since relapsed.

“Of interest, these relapses have been associated, at least in 4 patients at the biologically active dose, with changes in expression of CD22,” Fry said. “It appears to be different than with CD19. Where CD19 is lost completely in these patients, we saw largely a decrease in site density that we think drops the CD22 expression below the threshold for CAR activity.”

According to Fry, these data add to the notion that a single antigen-directed CAR immunotherapy probably will not be sufficient for long-term durable remissions in many patients, and points to the potential for targeting multiple cancer-related proteins.