Liso-Cel Improves Outcomes in Relapsed/Refractory Large B-Cell Lymphoma

Among patients with relapsed or refractory large B-cell lymphoma (LBCL), lisocabtagene maraleucel (liso-cel; Breyanzi) improved outcomes compared with the standard of care in the second-line setting, according to results of the international phase III TRANSFORM study, which were presented at the 2021 American Society of Hematology (ASH) annual meeting.

MedPage Today brought together three expert leaders in the field: moderator Ian Flinn, MD, of the Sarah Cannon Research Institute in Nashville, is joined by Loretta Nastoupil, MD, of the University of Texas MD Anderson Cancer Center, and Amitkumar Mehta, MD, of the University of Alabama at Birmingham, for a virtual roundtable discussion. This final of four exclusive episodes focuses on the findings from TRANSFORM.

Following is a transcript of their remarks:

Flinn: Hello, I'm Ian Flinn from the Sarah Cannon Research Institute in Nashville, Tennessee. I'm joined today by Loretta Nastoupil from the MD Anderson Cancer Center and Amit Mehta from University of Alabama at Birmingham.

The next study that I think we ought to talk about is the TRANSFORM trial, another large phase III trial comparing CAR T cells to standard-of-care chemotherapy and hopefully followed by autologous transplant if the patient has sensitive disease. Amit, what do you think about this trial? Maybe you could walk us through a little bit the design as well.

Mehta: Sure. So, TRANSFORM was another randomized trial comparing between CAR T and high-dose chemotherapy followed by liso-cel CAR-T infusion in patients with relapsed or refractory large B-cell lymphoma. This was similar to the other two studies that we discussed, a little bit different primary endpoint of event-free survival. This was an interim analysis, so this was not a final analysis, so they did not have as large a number of patients as the other two trials. But, impressively, the trial met the primary endpoint of event-free survival.

The control arm had event-free survival of 2 months compared to 10 months in the experimental arm. And also liso-cel, the side effect profile was very impressive as previously published, when it was initially approved. So, if you look at the CRS [cytokine release syndrome] and ICANS [immune effector cell-associated neurotoxicity] grade, they were relatively very, very low in this setting. So, it's another positive study. It was an interim analysis, very interesting. Third study in a row comparing CAR T versus transplant in relapsed/refractory large B-cell lymphoma setting.

Flinn: So, Loretta, you were an investigator on this trial. I wonder about your take on this and maybe also in comparison to some of the other studies. Liso-cel is another 4-1BB construct, unlike axi-cel [axicabtagene ciloleucel; Yescarta], which is CD28; there's differences in adverse events, but also similarities in terms of the construct with tisa-cel [tisagenlecleucel; Kymriah]. And so, a very different outcome here. What are your thoughts?

Nastoupil: I think the biggest challenge that we all have is we have three randomized studies done in a similar patient population, albeit with differences in terms of how the trials were conducted. But we have two studies that are positive. One with axi-cel, the CD28 co-stimulatory molecule, and liso-cel (TRANSFORM) with a 4-1BB. And I absolutely think that there is an advantage from a safety profile standpoint with 4-1BBs. It also lends itself to outpatient infusion. So, for some centers that might be an advantage.

I think the challenge though is still going to be the manufacturing. And so one of the advantages that axi-cel has is it's very reliable, relatively shorter turnaround time in terms of manufacturing. And so I think what I'm most excited about from the TRANSFORM study is it does appear that it is feasible to do liso-cel again in a high-risk patient population. They did allow for one cycle of salvage chemotherapy for patients who were enrolled onto the experimental arm. It did occur after leukapheresis.

I think the other debate that I'm hearing about now is, what is the harm in giving one cycle of salvage chemotherapy for those patients with early relapse, and then sending them on for that CAR-T evaluation? And I think that's a very reasonable consideration, but remember, these patients were collected prior to that one cycle of salvage chemotherapy. So, I still think that early referral, collect those cells off, sure, give one cycle of salvage chemotherapy to potentially optimize these patients. But there is still a trend in overall survival advantage for those patients who got CAR T in second line.

Flinn: Okay, thank you. I think three really important trials looking at the second-line therapy with CAR T cells in large B-cell lymphoma.

Watch Episode 1: Finally, a Positive Study in First-Line DLBCL Treatment. What Will it Mean?

Watch Episode 2: Is Second-Line Axi-Cel the New Standard in Aggressive B-Cell Lymphoma?

Watch Episode 3: CAR-T Trial Fails in Aggressive Large B-Cell Lymphoma

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