This was a three-year efficacy and longitudinal safety of lisocabtagene in patients with third line or later follicular lymphoma. It was the long-term outcomes of the TRANSCEND FL trial.

What was the study design?

The TRANSCEND FL trial was a phase II open-label, multicohort study for patients who were above the age of 18 with a diagnosis of relapsed/refractory follicular lymphoma. There was a second-line cohort for patients who had high-risk disease as well as a third-line and later cohort.  Patients received liso-cel after lymphodepletion as a one-time infusion and the primary endpoint was overall response rate with secondary endpoints of complete response, duration of response and progression free survival as well as safety.

What were the results?

This is a three-year follow-up of the TRANSCEND FL trial and there were efficacy subgroups for patients who were POD24, those who progressed within 24 months of treatment, patients with bulky disease, those who were double refractory, which included anti-CD20 antibody or alkylator, as well as patients who received prior bendamustine, looking at the time of treatment  with bendamustine. There were longitudinal safety analyses, including the assessment of cytopenias, B-cell aplasia, infections etc.

What was seen was that there was a very high response rate. So 97% overall response rate and 94% complete response rate in all patients with a median duration of response that has continued to not be reached. 70% of patients maintained their response at 36 months. When we look at the subgroup analysis, the overall response rates were 95% across all subgroups, and that included patients who had POD24, bulky disease or double refractory. Patients who received prior bendamustine there were some differences in terms of patients who had exposure to bendamustine less than 12 months from receiving infusion of cells, however, these were very small numbers, about five patients at that timepoint, so it’s hard to extrapolate the impact of the prior bendamustine. Patients who received bendamustine 12 months or more before infusion of liso-cel had no differences in their duration of response with the rest of the cohort.

The 36-month progression free survival rate for POD24 was 58%, 51% for bulky disease, 60% for double refractory. So those outcomes still show very durable high PFS rates.

What is the clinical significance of these results?

When we look across patients who have received liso-cel for follicular lymphoma, we see that this is a one-time treatment that has a significant disease-specific impact and patients have long durations of responses. There were no new safety signals and we see that long-term complications that we worry about, including infection, hypergammaglobulinemia, B-cell aplasia, secondary malignancy, do not show any significant changes above the two-year follow-up.

So for patients who receive a single infusion of liso-cell there are high rates of deep and durable responses with low infection rates. So potentially this is a key therapeutic benefit for patients with follicular lymphoma and potentially for some patients this is, in fact, a curative treatment.