A single infusion of a CD19-targeted CAR T-cell therapy can induce remissions lasting at least ten years in heavily pretreated patients with B-cell non-Hodgkin lymphoma. Researchers at the University of Pennsylvania in Philadelphia reported the findings, showing that no new relapses occurred after 5.4 years of follow-up in the evaluated cohort.
Ten-Year Survival Rates for Lymphoma Subtypes
The long-term clinical trial evaluated 38 patients with recurrent or refractory B-cell non-Hodgkin lymphoma, consisting of 24 patients with large B-cell lymphoma and 14 with follicular lymphoma. Ruella and colleagues at the University of Pennsylvania administered autologous T cells modified using a lentiviral vector to express a CD19-directed, 4-1BB-costimulated chimeric antigen receptor, known in its development stage as CTL019 or tisagenlecleucel. With a median follow-up of 10.1 years and a data cut-off of October 1, 2025, the estimated ten-year lymphoma-free survival reached 32% for large B-cell lymphoma and 47% for follicular lymphoma.
When factoring in deaths from other causes, the ten-year progression-free survival dropped to 17% for large B-cell lymphoma and 29% for follicular lymphoma. Overall survival at the ten-year mark stood at 17% for large B-cell lymphoma patients and 50% for follicular lymphoma patients. Among individuals who achieved an initial response, the Kaplan-Meier estimate for the continuation of that response at ten years was 57% overall, breaking down to 54% for large B-cell lymphoma and 60% for follicular lymphoma.
Late Health Risks and Persistent Side Effects
The longevity of these remissions was accompanied by documented late health complications. Nine patients developed a second primary malignancy, resulting in a ten-year cumulative incidence rate of 21%. Non-relapse-related mortality reached 18% at ten years, a figure that decreased to 14% when excluding COVID-19-related deaths. Grade 2 or 3 neutropenia persisted in two patients, though late anemia and thrombocytopenia were not observed.
B-cell aplasia continued in 44% of patients maintaining a long-term response. This finding indicates ongoing activity of the engineered CAR T cells, but it also creates a sustained shortage of normal B cells that can increase patient vulnerability to infections. Consequently, these individuals may require ongoing intravenous immunoglobulin substitution therapy. Investigators also observed that greater persistence of the CAR transgene during the first two years after infusion correlated with sustained responses, supporting a biological mechanism for durable disease control without confirming direct causation.
Clinical Implications of Extended Remission
The absence of any relapses beyond the 5.4-year mark indicates that patients maintaining a complete remission for this duration face a very low risk of late disease return. This pattern contrasts with standard systemic therapies for follicular lymphoma, which carry a known risk of late recurrence. However, investigators emphasize that these findings do not establish CAR T-cell therapy as a universally guaranteed cure without exception.
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