ASCO 2024 | 3-year follow-up from the TRANSFORM trial: liso-cel is superior to SoC in R/R DLBCL

The TRANSFORM study is a randomized, Phase III pivotal study investigating lisocabtagene maraleucel, which is a CD19, CAR-T cell therapy product against standard of care, which has been the age old standard of care for nearly two decades, which is autotransplant prior to which patients get salvage chemotherapy. And this study compares lisocabtagene maraleucel versus the standard of care in high risk, relapsed refractory diffuse large B-cell lymphoma in the second line setting.

The interim analysis, which was at a median follow-up of six months and then subsequently the primary analysis at a median follow-up of 17 months, demonstrated the ongoing superiority of lisocabtagene maraleucel versus standard of care in high risk relapsed refractory large B-cell lymphoma in the second line setting. And thus lisocabtagene is now approved as the new standard of care for patients with high risk relapsed refractory large B-cell lymphoma.

At ASCO this year, on behalf of my co-authors, I have been given the opportunity to present this abstract now at a median follow-up of three years, technically a median follow-up of 33.9 months. So just to quickly refresh everyone’s memory, the TRANSFORM study randomized patients with transplant eligible, high risk relapsed refractory large B-cell lymphoma between the age groups of 18 and 75, in a 1 to 1 fashion, to getting either lisocabtagene versus salvage chemo, followed by autotransplant in responders. I do have to make a mention here that nearly 62% of patients crossed over from the standard of care arm to liso-cel on this study. Crossover was built in within the study. The primary endpoint of this study is event free survival. And now we have 47% of patients at a median follow-up of three years that are on long term follow-up. On the other hand 27% of patients on the standard of care arm that are being actively followed. The median EFS on the lisocabtagene maraleucel is 29 months versus the median EFS from the standard of care arm is 2.4 months. Similarly, the overall response rates were superior on the lisocabtagene versus the standard of care arm. With regards to complete response rates, they remain the same and higher on the liso-cel arm versus standard of care. With regards to median PFS, it’s not reached versus only six months on the standard of care arm. The median overall survival is numerically higher on the liso-cel arm versus the standard of care. However, 62% of patients on the standard of care were crossed over to the liso-cel arm, so at this time point, the median overall survival is not reached in both of these arms.

With regards to adverse events, there were no new signals seen with regards to new toxicities, especially with regards to second primary malignancies. There were no evidence of T-cell malignancies in either arm. In regards to death, there were higher incidence of death in patients who got standard of care, including crossover versus liso-cel. With regards to toxicity of particular interest, which is related to CAR-T cell therapy, for example cytokine release syndrome, again, to allude to the efficacy as well as the safety of the product, there were no grade four or grade five toxicities with regards to cytokine release syndrome or neurological toxicities on the liso-cel arm. With regards to long term toxicities as well, majority of the toxicities in the post treatment emergent period were seen with regards to cytopenias, 9% on the liso-cel, 5% on the standard of care arm.

So overall, in summary, at the three year time point, liso-cel continues to show its superiority over standard of care, thus making it to be a potentially curative option in high risk relapsed refractory large B-cell lymphoma patients who are transplant eligible. Thank you