TRANSFORM Data Support Liso-cel as Second-line Treatment for LBCL, Says Dr Jeremy Abramson

The TRANSFORM data presented at the 64th American Society of Hematology Annual Meeting and Exposition confirm findings published last year on lisocabtagene maraleucel (liso-cel) in second-line treatment. Jeremy Abramson, MD, director of the lymphoma program, Massachusetts General Hospital Cancer Center, expands on these new insights for patients with high-risk relapsed/refractory large B-cell lymphoma, and the importance of the longer follow-up period.

Transcript

How do the TRANSFORM data being presented this year confirm and build on last year’s findings?

There are a number of insights that we now have with the primary analysis that we didn't have yet at the time of the interim analysis with a median follow-up of 6 months. Now, with 17.5 months of median follow-up in the primary analysis of TRANSFORM, we can be confident in the durability of these responses. We see a plateau on our progression-free and event-free survival curves, providing comfort that these are deep and durable remissions, which is difficult to discern when you only have 6 months of median follow-up. We also have longer follow-up in the standard of care arm, and with longer follow up in the standard of care arm, we're seeing that the standard of care continues to underperform historically relative to this new, modern treatment. The fact that two thirds of patients assigned to what has been our standard treatment have been failed by that treatment and approved for crossover to liso-cel tells us that the standard of care is failing the vast majority of patients. Thankfully, we have these new products that allow us to move on from there.

We also can glean some insights from these patients who crossed over to receive liso-cel as a third-line treatment on this trial. Among these two-thirds of patients assigned to standard of care who crossed over to receive liso-cel, the median time from approval to crossover to receipt of liso-cel was quick at 15 days. However, what we saw is that the complete response rate, progression-free, and overall survival for these patients was actually inferior to patients who receive liso-cel on the liso-cel arm as second-line treatment in this trial. What that suggests to me is that earlier treatment with liso-cel in the second-line, rather than the third-line setting as possible, is going to maximize the cure rate for our patients.

How were patients from the standard-of-care arm able to cross over to receive liso-cel?

Patients on the standard-of-care arm all underwent leukapheresis prior to the randomization. So before we even knew whether patients will be in the liso-cel arm or the standard-of-care arm, all patients [underwent leukapheresis]. What that meant was we had all patients' T cells and generated liso-cel product on all of them. What that meant is that, if a patient who was assigned to the standard-of-care either did not respond, progressed, or relapsed on the standard-of-care arm, we already had liso-cel available for that patient and so the crossover was effectively immediate.

Now, I should note that that isn't something that would happen in the real-world setting. In the real-world setting, if a patient received a second-line treatment, such as R-ICE [rituximab, ifosfamide, carboplatin, and etoposide phosphate] or R-DHAP [rituximab, dexamethasone, high-dose cytarabine, and cisplatinor] or R-GDP [rituximab, gemcitabine, cisplatin, and dexamethasone], and they failed to respond to that treatment, they would then have to undergo leukapheresis, the manufacturing period, and ultimately receive their CAR T-cell product in a much more delayed fashion than we were allowed to do on this study, which I think really helped us optimize the treatment for the patients assigned to the standard-of care arm.