ASCO 2026 | Longitudinal safety of liso-cel in patients with second-line or later large B-cell lymphoma

At ASCO 2026, we are presenting a longitudinal pooled safety analysis of lisocabtagene maraleucel, herein referred to as liso-cel, in patients with second-line or greater diffuse large B-cell lymphoma. With regards to CAR T-cell therapy, it has certainly changed outcomes in patients with relapsed DLBCL, offering them a cure of about 40% in third line and about 50% to 55% in second line. So given that this is curative intent treatment, it’s very important that access also be increased so that everybody who is eligible for liso-cel can get it. So with that in mind, we also know that the most recent regulatory requirements have actually shortened the liso-cel post-infusion monitoring period from what it used to be, which was four weeks to two weeks at the CAR-T treating site. And driving restrictions have now decreased from eight weeks to two weeks as well. So I do believe that this is a huge change for patients in order to get them CAR T-cell therapy and increase access. 

So with regards to increasing access, it would also mean that patients are returning home to their primary oncology clinics. And what does it mean for the community partners to be able to take care of patients with regards to safety post CAR T-cell therapy? So the intent was to really figure out that we understand the acute first two weeks of CRS and ICANS that we expect, but what does it actually look like when patients transition back to their homes with their oncology providers? And with that in mind, we conducted this longitudinal safety pooled analysis across three pivotal studies: TRANSFORM, looking at liso-cel in second line; PILOT, looking at liso-cel in transplant-ineligible second line and higher; and then TRANSCEND, in patients who had received liso-cel more than two lines of treatment. We included a total of 420 patients. And the key parameters that we looked at were primarily the incidence of grade 3 or higher cytopenias, the requirement to give them supportive care, whether it’s growth factor support or transfusions, the incidence of grade 3 or higher infection, and the recovery of immune reconstitution after having been exposed to CAR T-cell therapy. And the last variable we looked at was second primary malignancy. 

So hitting at the key points here with regards to grade 3 and higher cytopenias, fortunately, after the first few days and weeks, it’s actually quite low. So breaking it down with regards to grade three or higher anemia, it was the highest in the first 15 days and it then drastically reduced. And subsequently, after the first three months, the need for any kind of transfusion support was minimal, and grade three or higher anemia was down to less than 5%. The same trend was also observed with neutropenia. So grade 3 or higher neutropenia was 87% in the first 15 days and then drastically shortened after the first three months, going down to actually less than 5% again. Grade 3 or higher thrombocytopenia was actually seen in about one-third of the patient population for the first three months, and then after month 9, the incidence of grade 3 or higher thrombocytopenia went down to less than or equal to 3%. Now, the big question is, what does infection risk look like as a result of the neutropenia? And this was a very reassuring analysis to see that for the first three months, grade three and higher infection risk was at a range of two to six percent. And then after three months, it actually went down to one to two percent. So it really helps assure the community provider that the incidence of grade three or higher infection is quite drastically low. 

The big question is CAR-T causes B cell aplasia, CAR-T causes hypogammaglobulinemia. What does the recovery pattern look like? With regards to hypogammaglobulinemia, about 41% actually had full recovery by two years. And then with regards to B-cell aplasia, it was lower at 26% by two years. The most reassuring part of this is despite these immune changes, it did not translate into higher risk of infection. And last but not least, the risk of second primary malignancies as a result of antecedent treatments, including CAR T-cell therapy. Fortunately, it was extremely low. And at this point, we only found one T-cell lymphoma over 420 patients. So overall, the incidence was quite low. And this basically supports outpatient management of CAR T-cell therapy, really assuring community providers to take their patients back around day 15 if they’re doing well.

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