Subscribe
VBCC - February 2014, Volume 5, No 1 - Personalized Medicine
Phoebe Starr

New Orleans, LA—Mounting evidence from several research centers shows that autologous T-cells genetically engineered with a chimeric antigen receptor-T (CAR-T; also called CTL019) achieve dramatic responses in patients with advanced leukemia and lymphoma who have exhausted all treatment options.

At the 2013 American Society of Hematology meeting, many oral sessions and posters focused on the use of CAR-T cells in acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and B-cell lymphoma. The centers doing this research use varying protocols, but the principle approach is the same.

The patient’s own T-cells are extracted and genetically engineered ex vivo to target the CD19 antigen present on cancer cells; a viral vector is inserted, and the cells are reinfused into the patient via a single infusion where they are designed to expand and attack cancer cells like a “smart bomb.” Currently, it takes approximately 10 days to engineer the cells.

“It looks like the disease has disappeared after a single infusion of these engineered T-cells,” reported James N. Kochenderfer, MD, from the Experimental Transplantation and Immunology Branch of the National Cancer Institute (NCI).

Acute Lymphoblastic Leukemia
A total of 22 pediatric patients and 5 adult patients with relapsed, treatment-resistant ALL have been treated with CTL019 at the University of Pennsylvania, said Stephan A. Grupp, MD, PhD, Director, Translational Research, Center for Childhood Can­cer Research, Children’s Hospital of Philadelphia, PA.

Of these patients, 19 achieved complete remission (CR), 14 of them still ongoing; 5 patients relapsed. The first patient treated with the protocol is now 8 years old and has been in CR for 20 months.

Of the 5 adults, 4 achieved CR, the longest of which has been 6 months. One patient subsequently underwent bone marrow transplant and remained in remission. One patient relapsed after being 3 months in CR, and his disease tested negative for the engineered cell target.

A separate report from the Uni­versity of Pennsylvania described the fate of the CTL019 cells after they were reinfused into the population that was discussed by Dr Grupp above. The lead investigator was Michael Kalos, PhD, Adjunct Associate Professor of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.

Patients with the greatest magnitude of in vivo expansion of the reengineered T-cells (above 5% of the total of all their T-cells) were most likely to achieve CR, patients with a lesser response but detectable levels of cell expansion were partial responders, and those with no detectable T-cell expansion were nonresponders. The reinfused T-cells remained in the body several months postinfusion and were viable.

Chronic Lymphocytic Leukemia
CTL019 cells have been used to treat 32 adults with CLL by David L. Porter, MD, Director, Blood and Marrow Transplantation, Abramson Cancer Center, University of Pennsylvania, and colleagues. The overall response rate is 47% (15/32), including 7 CRs (still on­going) and 15 partial responses (PRs).

These 32 patients included 14 patients in a pilot trial and the first 18 in a phase 2, dose-optimization trial.

Some of the remissions have lasted for >3 years, suggesting that the T-cells continue to do their work over time. Some PRs converted to CRs over time, Dr Porter said.

B-Cell Lymphoma: First Report
Dr Kochenderfer presented results from the NCI’s study of 15 patients (age, 30-68 years) with B-cell lymphomas, including 9 with chemotherapy-refractory disease (some up to 10 previous cycles of treatment) and 6 had a variety of indolent B-cell lymphomas.

“We are particularly encouraged by the partial and complete responses that we observed in a number of patients with diffuse large B-cell lymphomas who had exhausted all other treatment options,” Dr Kochenderfer said.

Overall, 7 patients achieved CR and 5 achieved PR; 1 patient died from cardiac arrhythmias, and 1 patient was lost to follow-up.

Acute toxicities included fever, low blood pressure, focal neurological deficits, and delirium, all of which resolved in less than 3 weeks.

“This is the first true glimpse of the potential of this approach in patients with aggressive lymphomas that, until this point, were virtually untreatable and have a very poor prognosis. The novel finding is that CTL019 can eradicate solid tumor mass,” Dr Kochenderfer said at a press conference. This approach could be used for patients who are not suitable for transplant, he noted.

Industry Buy-In
These exciting, often dramatic responses have attracted industry partnerships. For example, the Fred Hutchinson Cancer Research Center, Memorial Sloan-Kettering Cancer Center, and the Seattle Children’s Re­search Institute collectively launched Juno Therapeutics Inc, a new biotechnology company to develop CTL019 cells. The NCI has licensed their CTL019 cells to Kite Pharmaceuticals. The University of Pennsylvania has partnered with Novartis to develop CTL019 cells, and Novartis is building a manufacturing facility at the University of Pennsylvania.

Experts estimate that CTL019 will be available as a treatment option between 2016 and 2020.

Related Items
Tocilizumab Demonstrates Success in the Treatment of Patients with Giant Cell Arteritis
Phoebe Starr
VBCR - December 2016, Vol 5, No 6 published on January 5, 2017 in Giant Cell Arteritis
Rituximab Maintenance Outshines Azathioprine for Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis
Phoebe Starr
VBCR - December 2016, Vol 5, No 6 published on January 5, 2017 in Vasculitis
Cost of Drugs and Affordability Don’t Always Jibe
Phoebe Starr
VBCC - July 2016, Vol 7, No 6 published on July 13, 2016 in Value in Oncology
Usefulness of Vitamin D Supplementation Questioned in Patients with Knee Osteoarthritis
Phoebe Starr
VBCR - June 2016, Vol 5, No 3 published on July 7, 2016 in Osteoarthritis
Baricitinib Effective in Patients with Refractory Rheumatoid Arthritis
Phoebe Starr
VBCR - June 2016, Vol 5, No 3 published on July 7, 2016 in Rheumatoid Arthritis
Vaccine Uptake Remains Low in Patients with RA
Phoebe Starr
VBCR - June 2016, Vol 5, No 3 published on July 7, 2016 in Health & Wellness
Age, Smoking History Are Risk Factors for Early Organ Damage in Patients with SLE
Phoebe Starr
VBCR - June 2016, Vol 5, No 3 published on July 7, 2016 in Lupus
IL-6 Inhibitor Shows Promise in Patients with PsA
Phoebe Starr
VBCR - June 2016, Vol 5, No 3 published on July 7, 2016 in Psoriatic Arthritis
Mutation Testing Encouraged for All Patients with Ovarian Cancer
Charles Bankhead
VBCC - June 2016, Vol 7, No 5 published on June 17, 2016 in Personalized Medicine
ESR1 Mutations Predict Worse Survival in ER-Positive Advanced Breast Cancer
Phoebe Starr
VBCC - June 2016, Vol 7, No 5 published on June 17, 2016 in Personalized Medicine
Last modified: May 28, 2014
  • Rheumatology Practice Management
  • Lynx CME
  • American Health & Drug Benefits
  • Value-Based Cancer Care
  • Value-Based Care in Myeloma
  • Value-Based Care in Neurology