CTL019 Cells Can Induce Potent, Durable Responses in Relapsed/Refractory ALL
NEW ORLEANS—CTL019 cells can induce potent and durable responses in both children and adults with relapsed/refractory acute lymphoblastic leukemia (ALL), a pilot study reported at the 55th American Society of Hematology Annual Meeting and Exposition has found.
T cells engineered with a chimeric antigen receptor that target CD19 (CTL019) produced significant in vivo proliferation, complete responses, and long-term persistence without graft-versus-host disease (GVHD), said Stephan A. Grupp, MD, PhD, Children's Hospital of Philadelphia, Philadelphia, PA.
To date, Dr. Grupp and colleagues have treated more than 60 patients with CLL and ALL with CTL019. In the results presented during the meeting, he noted 19 of 22 children (86%) had complete responses; five subsequently relapsed, including one CD19(-) relapse. Among all patients with ALL (n = 27; pediatric and adult), 24 complete responses (89%) were observed, of whom six relapsed. He pointed out that follow-up was short, a median of 3.4 months (range, 2-18 months).
A total of 16 patients had post-allogeneic stem cell transplant (SCT). When T cells were collected from patients, no evident of GVHD was observed 6 months after SCT. Median donor chimerism was 100%.
All patients who responded developed some degree of delayed cytokine release syndrome (CRS) concurrent with peak T-cell expansion that was manifested by fever, with variable degrees of myalgias, nausea, or anorexia, Dr. Grupp noted. Some experienced transient hypotension and hypoxia.
Detailed cytokine analysis showed marked increases from baseline values of interleukin-6, interferon-γ, interleukin-2R, and granulocyte macrophage colony stimulating factors, with elevations in IL-6 correlating with CRS.
“CTL019 therapy is associated with a significant CRS that responds rapidly to IL-6-targeted anti-cytokine treatment,” Dr. Grupp said. “This approach has promise as a salvage therapy for patients who relapse after allo-SCT, and collection of tolerized cells from the recipient appears to have a low risk of GVHD.”
Multicenter trials are being developed to test this therapy for ALL in the phase 2 setting, he added.
He also presented information about the IL-6 receptor antagonist tocilizumab, which blocks IL-mediated effects. The agent is indicated for the treatment of juvenile idiopathic arthritis and rheumatoid arthritis, and in Japan for Castleman's disease. Typically given monthly, rare adverse events associated with tocilizumab include transaminitis and neutropenia. To date, Dr. Grupp and colleagues have used 8 mg/kg in patients with CLL.