Liso-Cel a Potential New CAR-T Option for High-Risk R/R Follicular Lymphoma

Patients with high-risk relapsed/refractory follicular lymphoma experienced statistically significant and clinically meaningful responses when treated with lisocabtagene maraleucel (liso-cel; Breyanzi) as second-line therapy, according to primary analysis results from the phase II TRANSCEND FL study presented atthe recent American Society of Hematology (ASH) annual meeting.

In this third of four exclusive episodes, MedPage Today brought together three expert leaders in the field, all from Ohio State University Wexner Medical Center in Columbus — moderator Kami Maddocks, MD, is joined by Yazeed Sawalha, MD, and David Bond, MD — for a virtual roundtable discussion on the encouraging results on the CD19-directed chimeric antigen receptor (CAR) T-cell therapy in this setting.

Following is a transcript of their remarks:

Maddocks: So let’s move on to our next abstract. So this is the TRANSCEND follicular study. So this was phase II study primary analysis of the liso-cel product as second-line therapy in patients with high-risk relapsed or refractory follicular lymphoma. So currently not a product that’s approved for this indication and currently no indication in the second line. Let’s talk through this data and what was seen in this trial.

Bond: Yeah, exciting to see data second line for follicular lymphoma, we’ve seen in diffuse large B-cell lymphoma that there’s been a role for CAR-T therapy and with two drugs, including lisocabtagene maraleucel, which is the drug that was being studied in the study.

And so we have a growing amount of experience in large B-cell lymphoma with liso-cel as I’ll call it. And we see that it’s a product similar to tisagenlecleucel [Kymriah] that tends to have a lower rate of CRS [cytokine release syndrome] compared to axicabtagene ciloleucel [Yescarta] and potentially more manageable to be in an outpatient setting. And you see a fairly small study, but you see in high-risk patients — these are patients with either POD24 [progression of disease within 2 years] or a high disease burden — that at 12 months the median PFS [progression-free survival] was impressive, 91%. So really promising that in patients that were using this earlier on in therapy where there may be more fitness of their immune cells, you see very promising efficacy.

But again, it’s a small number of patients so I think we can’t make any definitive conclusions, but based on what we’re seeing here, definitely warrants further investigation early on for these highest risk patients I think.

Sawalha: Yeah, I agree. Very small study, only 23 patients actually infused. Very short follow-up, but CR [complete response] rate of 96%, quite remarkable. And the safety, no signals of excessive toxicity in this patient population. So very, very encouraging data. I’m looking forward to seeing more results here too.

I think again, to your point Dr. Maddocks, its sequencing in follicular lymphoma, it’s going to be very interesting to see how things are going to roll in the next few years with the bispecifics and CAR-T and other novel agents as well.

Maddocks: So if you thought about it right now, are there certain or particular, probably as indicated in this study, what patient populations of follicular would you think second-line CAR would be a good option [for] if available?

Bond: I think that [for] the patients that there’s a high suspicion for transformed disease, because sometimes there are patients that we don’t have a biopsy that has confirmed transformed disease but there’s very high clinical suspicion, and maybe the most avid area is not accessible to biopsy. I think that those patients in my mind, just given that the known efficacy of CAR-T therapy with large B-cell lymphoma, I think those are a situation. And then I guess for a high-risk patient, I think a clinical trial with a CAR-T product is worth considering second line if you have somebody with early relapse. But I think, in my mind, those are the two settings where I would think of it currently.

Sawalha: Yeah, I was going to say exactly the same.

Maddocks: OK, great. So we look forward to more CAR T-cell in follicular lymphoma.