TOPLINE:

A single infusion of tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell therapy, produces decade-long remissions in approximately one third of patients with heavily pretreated large B-cell lymphomas and nearly half of those with follicular lymphoma. At a median follow-up of 10.1 years among 38 patients, no relapses occurred beyond 5.4 years, with 10-year lymphoma-free survival of 32% for large B-cell lymphoma and 47% for follicular lymphoma.

METHODOLOGY:

• Approximately 30%-50% of patients with relapsed or refractory B-cell non-Hodgkin lymphomas have achieved durable remissions with CAR T-cell therapies targeting CD19 over follow-up periods of up to 5 years. The durability of remissions beyond 5 years and the curative potential of CAR T-cell therapy remain unclear, as late recurrences after chemoimmunotherapy are well recognized in lymphoma patients.
• Researchers evaluated long-term outcomes in 38 patients with relapsed or refractory B-cell non-Hodgkin lymphomas (24 with large B-cell lymphoma and 14 with follicular lymphoma) who received CTL019 (now called tisagenlecleucel) at the University of Pennsylvania in Philadelphia.
• Participants received autologous T cells transduced via a lentiviral vector to express CD19-directed, 4-1BB-costimulated chimeric antigen receptors, with all products manufactured at the University of Pennsylvania.
• Lymphoma-free survival was defined as time from tisagenlecleucel infusion to lymphoma relapse or lymphoma-related death, with deaths unrelated to lymphoma censored at the time of death.
• Patients in continuous complete remission for ≥ 5.5 years without additional treatment after tisagenlecleucel infusion were considered to have a long-term response, based on the last observed relapse at 5.4 years.

TAKEAWAY:

• At 10 years, lymphoma-free survival was 32% among patients with large B-cell lymphoma and 47% among those with follicular lymphoma.
• The 10-year progression-free survival was 17% among patients with large B-cell lymphoma and 29% among those with follicular lymphoma, while 10-year overall survival was 17% and 50%, respectively.
• Among patients with a response, the Kaplan-Meier estimate of continued response at 10 years was 57% overall, 54% for large B-cell lymphoma, and 60% for follicular lymphoma.
• Higher CAR-transgene persistence over the first 2 years after infusion appeared to be associated with long-term response, and B-cell aplasia persisted in 44% of patients with a long-term response at the data-cutoff date.

IN PRACTICE:

“These 10-year data confirm that early survival curve plateaus may predict durable remissions, which is unlike the results seen with chemoimmunotherapy or bispecific antibody therapies, which are more frequently characterized by late relapses, especially in patients with follicular lymphoma,” wrote the authors of the study.

“Our findings support the hypothesis that patients with a long-term response to CAR T-cell therapy may be cured — including patients with heavily pretreated large B-cell lymphomas or follicular lymphoma, who are generally considered to have incurable disease,” they said.

SOURCE:

The study was led by Marco Ruella, MD, Luca Paruzzo, MD, and Stephen J. Schuster, MD, Perelman School of Medicine at the University of Pennsylvania. It was published online on June 25 in The New England Journal of Medicine.

LIMITATIONS:

According to the authors, the study is limited by its single-center design and modest sample size. The lack of systematically collected correlative data at late time points precludes a conclusive, detailed characterization of immune-cell subset reconstitution and mechanisms underlying specific second primary cancers. 

DISCLOSURES:

The study received support from the Richard Berman Family Innovations Center in CLL and Lymphomas, the Maguire Family Fund for Lymphoma Research, the Laffey-McHugh Foundation, and a National Cancer Institute Research Program Project Grant. The original study received funding from Novartis and a grant from the National Institutes of Health. Ruella and Carl H. June, MD, disclosed receiving support from the National Cancer Institute grant, while Jakub Svoboda, MD, disclosed support from the Laffey-McHugh Foundation, and Schuster disclosed support from the Richard Berman Family Innovations Center and the Maguire Family Fund. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.