Ten-Year Outcomes With Tisagenlecleucel Demonstrate Durable Remissions in B-Cell Lymphoma

Clinical Summary: 

• Design/Population: Long-term follow-up of patients with relapsed or refractory diffuse large B-cell lymphoma or follicular lymphoma treated with a single infusion of the CD19-directed CAR T-cell therapy tisagenlecleucel. 
• Key Outcomes: A substantial proportion of patients remained lymphoma-free 10 years after treatment, demonstrating durable remissions following a single CAR T-cell infusion. Long-term responses were associated with CAR T-cell persistence, and late safety findings highlighted the importance of monitoring for infections and secondary malignancies.
• Clinical Relevance: These data provide evidence supporting the long-term curative potential of CD19-directed CAR T-cell therapy while emphasizing the need for continued survivorship monitoring and development of next-generation cellular therapies.

Marco Ruella, MD, University of Pennsylvania, Philadelphia, Pennsylvania, discusses 10-year follow-up of patients with relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma treated with tisagenlecleucel, highlighting the long-term durability of CD19-directed CAR T-cell therapy.

The analysis demonstrates that durable remissions can extend beyond a decade after a single CAR T-cell infusion and suggests that long-term CAR T-cell persistence may contribute to sustained disease control. Dr Ruella also discusses how these findings inform future efforts to move CAR T-cell therapy into earlier treatment settings while improving safety, manufacturing, and long-term outcomes.

Transcript: 

Hi, my name is Marco Ruella. I am a physician at the University of Pennsylvania, I'm also the scientific director of the lymphoma program there. I'm very excited to talk to you about our recent paper that was published in the New England Journal of Medicine.

This paper looks at the long-term follow-up of 38 patients with diffuse large B-cell lymphoma and follicular lymphoma who were treated with CAR19, in particular a 4-1BB costimulated CAR 19. At the time, we called it CTL019, now it's called tisagenlecleucel. We looked at these 38 patients who were treated over 10 years ago, and we looked at their outcomes 10 years later.

I think what was pretty remarkable is that if we look at lymphoma-free survival, it was about 50% for follicular lymphoma and about 30% for diffuse large B-cell lymphoma. So what does that mean?

It means that one single infusion of engineered CAR T-cells can lead to very long remissions, and I would argue potentially cures, in a significant number of patients with diffuse large B-cell lymphoma or follicular lymphoma.

Over the 10 years of follow-up, some of the patients died from causes other than lymphoma. We looked at the various causes of death, and what we saw was that some of the deaths were due to causes that would also occur in an age-matched control population. But other causes of death included secondary malignancies in a number of patients, and unfortunately some patients died during the COVID pandemic.

Overall, I would say that this study highlights that one single infusion of CAR T-cells can lead to prolonged remission over the very long term—10 years. We think this is correlated with persistence of the CAR T-cells, at least at 2 years. We see that patients with CAR T-cell persistence at 2 years have a higher likelihood of remaining in remission over the long term.

At the same time, I think these data warrant very close follow-up of these patients because they can develop infections, they can develop secondary malignancies, and so while they remain in remission of their disease, they can still have complications related to their previous treatment and to the CAR T-cell therapy.

Thinking ahead, I think this study clearly shows that the potency of CAR T-cells extends beyond 10 years. These really are live drugs that can produce remissions lasting at least 10 years. Now the obvious question is: what are the effects of this therapy when we use it earlier during the course of treatment?

Keep in mind that for this study, the patients included in this study had relapsed or refractory disease after multiple prior lines of therapy. Now we're using CAR T-cells in the second-line setting, so we hope these patients will have even better outcomes at 10 years. At the same time, we hope they will experience fewer toxicities because they will have been exposed to fewer prior therapies. 

But we also need to think about how we can make CAR T-cells safer. For example, we've been very interested in developing CAR T-cells that specifically target malignant B-cells while sparing healthy B-cells. We published this work in Science Translational Medicine earlier this year, and that approach has the potential to spare patients from long-term B-cell aplasia.

Another important question is whether we can shorten manufacturing time. Can we potentially use in vivo CAR T-cell approaches? Certainly, I think this study really sets the bar for future CAR T-cell products in terms of long-term efficacy. 

Source: 

Ruella M, Paruzzo L, Chong ER, et al. Ten-year outcomes after CAR T-cell therapy for B-cell lymphomas. N Engl J Med. Published online: June 24, 2026. doi: 10.1056/NEJMoa2518035