T-Cell Therapy Has Lasting Effects

A T cell–based immunotherapy produces durable remissions in acute lymphocytic leukemia (ALL) and some B-cell lymphomas, according to data presented at the American Society of Hematology 57th Annual Meeting, held in Orlando, FL, December 5–8.

In the chimeric antigen receptor–modified T cell–based (CAR T) therapy, T cells isolated from patients are genetically engineered to recognize the B-cell marker CD19. These cells are then infused back into the patient, where they multiply and attack CD19-bearing tumor cells.

Stephan Grupp, MD, PhD, of The Children's Hospital of Philadelphia, PA, presented data from an ongoing pediatric trial of Novartis's CAR T therapy, CTL019. Among 59 children with relapsed or refractory ALL who received the therapy, 55 achieved complete remission (CR) within 1 month of therapy, a 93% response rate. With a median follow-up of 1 year, 34 (55%) were still in remission, with 18 patients maintaining a CR for a year or more. One patient has been in remission for 3.5 years.

The short-term activity of the treatment continues to be “phenomenal,” says Grupp. As the long-term data accumulate, Grupp says, “the numbers are a lot higher than you would expect and have not been seen before with non-cell therapies in this population.”

The 1-year survival rate in the trial was 79%, compared with 20% among similar patients who receive standard care.

In another study of CTL019, about half of a group of adults with relapsed or refractory B-cell non-Hodgkin lymphomas experienced CR, according to data presented by Stephen J. Schuster, MD, of the University of Pennsylvania School of Medicine in Philadelphia. The trial had a median follow-up of 14 months. All of the subjects had already exhausted available therapies; all had a poor prognosis.

Schuster reported that seven of 15 patients (47%) with refractory diffuse large B-cell lymphoma achieved a response after one infusion of CTL019. Eight of 11 patients with follicular lymphoma (73%) experienced a response, while one of two with mantle cell lymphoma showed a CR. Of the 15 responders with diffuse large B-cell or follicular lymphoma, 10 are still in remission after a year. The median duration of response has not been reached.

“This shows for the first time the durability of the response, and the fact that a single treatment can lead to a long-lasting response,” says Schuster. “That these people are alive beyond a year without disease is amazing, given the prognosis.”

The results “suggest this may be more than just a bridge to transplant or an alternative therapy, it may be an end in itself for therapy for some patients,” Schuster adds.

A common side effect of CTL019 was cytokine release syndrome (CRS), in which the attacking T cells overproduce cytokines, causing adverse events ranging from mild flu-like symptoms to life-threatening respiratory distress. CRS occurred in 88% of patients in the ALL study, with 28% of patients experiencing serious CRS requiring management with tocilizumab, an FDA-approved anti-IL6 drug. In the non-Hodgkin lymphoma trial, serious CRS was reported in only four patients.

Some relapses in the ALL trial resulted from acquired resistance to the CAR T cells. Of the 20 children who relapsed, 13 developed CD19-negative tumors. In the non-Hodgkin lymphoma trial, CD19-negative relapses were generally not seen—patients either responded durably or usually relapsed with CD19-positive tumors.

Novartis is testing CTL019 in two phase II international, multisite trials for pediatric ALL and adult B-cell lymphomas, and aims to apply for FDA approval by the end of 2016. Three other companies are also testing CD19-targeted CAR T-cell treatments. –Pat McCaffrey

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