ASH 2015: High Response Rates, Long-Term Remissions in Relapsed/Refractory Pediatric ALL, Lymphomas After CTL019 Immunotherapy
Ninety-three percent of pediatric patients (55 of 59) with relapsed/refractory acute lymphoblastic leukemia (ALL) went into remission after receiving an investigational therapy made from their own immune cells, with continuous remissions of over 1 year in 18 patients and over 2 years in nine patients. In an emerging new use of the same therapy, known as CTL019, more than half of patients (15 of 28) with non-Hodgkin lymphoma (NHL) also responded to infusions of the personalized cellular therapy.
Findings from these two clinical trials, conducted by researchers from the Perelman School of Medicine at the University of Pennsylvania and The Children's Hospital of Philadelphia, were presented during the 57th American Society of Hematology (ASH) Annual Meeting. The results expand Penn's work with chimeric antigen receptor (CAR) therapies, building on initial findings in patients with chronic lymphocytic leukemia dating back to the start of the first Penn clinical trial of CTL019 in 2010.
“With each child we treat as part of this trial, we learn more about the potential of CTL019 to help patients whose cancers cannot be controlled with conventional therapies,” said Stephan Grupp, MD, PhD, the Yetta Deitch Novotny Professor of Pediatrics in Penn’s Perelman School of Medicine and Director of the Cancer Immunotherapy Frontier Program at The Children's Hospital of Philadelphia. “The response rate and durability we are seeing are unprecedented, and gives us hope that personalized cellular therapies will be a powerful key to long-term control of this difficult cancer.”
ALL
Dr. Grupp presented results (Abstract 681) from a trial of 59 children with relapsed/refractory ALL infused with CTL019 cells, in which 55 (93%) experienced complete remissions, with an overall 1-year survival of 79%. Relapse-free survival at 6 months was 76%, and 55% at 1 year. With a median follow-up of 12 months, 34 patients remain in complete remission, with six undergoing additional treatments such as stem cell transplant. Among 20 patients who relapsed, three saw their disease come back after additional therapies, and 13 patients’ cancers returned with CD19-negative cells, which are not amenable to targeting with CTL019.
Lymphomas
In a study presented by Stephen Schuster, MD, the Robert and Margarita Louis-Dreyfus Associate Professor in Chronic Lymphocytic Leukemia and Lymphoma Clinical Care and Research in Penn's Abramson Cancer Center and Perelman School of Medicine (Abstract 183), 57% of patients (15 of 28 evaluable patients) in the NHL trial had responded to CTL019 therapy by 3 months post-cellular infusion. Response rates were 72% (8 of 11 patients) among patients with follicular lymphoma, 47% (7 out of 15 patients) in diffuse large B-cell lymphoma, and 50% in mantle cell lymphoma (1 of 2 patients). Overall, 14 patients experienced complete remissions of their disease. All patients had stopped responding to conventional therapies before receiving the investigational cellular therapy, including, in many cases, stem cell transplants. Median progression-free survival among the responding patients with follicular lymphoma and diffuse large B cell lymphoma has not yet been reached after a median follow-up of 14+ months.
“The field of immunotherapy has provided an array of promising new investigational treatments for blood cancers in the past few years, and our early results in this trial provides increasing evidence for the role of personalized cellular therapies in patients with non-Hodgkin lymphoma,” said Dr. Schuster.
CTL019
The investigational therapy, CTL019, begins with each patient's own T cells, collected through a procedure similar to dialysis. The cells are then reprogrammed in a laboratory to hunt and potentially kill cancer cells in the patient's body. After the patient undergoes lymphodepleting chemotherapy, they receive an infusion of their newly engineered cells. The modified T cells contain an antibody-like protein known CAR, which is designed to target the CD19 protein found on the surface of B cells, including the cancerous B cells that characterize both ALL and NHL. The modified “hunter” cells are then infused back into the patient's body, where they multiply and are believed to attack the cancer cells. A signaling domain built into the CAR promotes rapid multiplication of the modified cells that tests reveal can grow to more than 10,000 new cells for each single engineered cell patients receive.
Side Effects
Some patients who received the investigational T cell therapy developed cytokine release syndrome (CRS) within several weeks after their infusions, typically during the time when the modified cells expanded to their greatest number in the body. This condition includes varying degrees of flu-like symptoms, with high fevers, nausea, and muscle pain; neurologic symptoms including hallucinations and delirium; and, in more severe cases, low blood pressure and breathing difficulties which may require intensive care. Eighteen of the lymphoma patients experienced CRS. In the pediatric ALL trial, 88% of patients developed CRS. The CHOP/Penn team has developed a management strategy to treat these side effects, including the IL-6 blocking drug tocilizumab. All patients in these two trials recovered from their CRS. One lymphoma patient suffered from severe encephalitis several months after receiving their cells.
Because CTL019 is an investigational therapy, the safety and efficacy profile has not yet been established.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
