ASH 2025 | Long-term follow-up of TRANSFORM: liso-cel versus SOC for R/R LBCL

The TRANSFORM study is a Phase III global randomized study investigating lisocabtagene maraleucel, also called liso-cel, which is an autologous CD19-directed CAR T-cell therapy. And this construct was tested head-to-head against the then standard of care, which was salvage chemo followed by an auto-transplant in patients with high-risk, second-line, large B-cell lymphoma. The TRANSFORM study is a positive study. Liso-cel showed high efficacy, manageable safety, and a superior and a statistically significant event-free survival, progression-free survival compared to the standard of care, and thus is now the new standard of care for patients with high-risk, meaning primary refractory or early relapsing second-line large B-cell lymphoma. Upon completion of the TRANSFORM study, patients had the ability to enroll in a separate long-term follow-up protocol herein called the LTFU. On the LTFU contained patients who received liso-cel and were followed for three years and then enrolled into LTFU. It also consisted of patients who progressed on standard of care, crossed over, received liso-cel, were followed for 12 months, and then enrolled on to LTFU. So, LTFU basically consisted of patients who were liso-cel-treated in second line and third line as a function of the crossover. 184 patients on the TRANSFORM study were randomized, liso-cel to 92, standard of care 92, and eventually, on the long-term follow-up protocol, 43 patients with liso-cel were on the LTFU protocol. And from the standard of care who received liso-cel were 23 patients on the LTFU protocol. The baseline characteristics were equivalent between the two groups. Now, let’s take a look at the data. The data basically tells us that at the four-year mark, the progression-free survival for patients who got liso-cell was 62%. The four-year progression-free survival is excellent, but so is the overall survival. The four-year OS is 52%. Now, let’s look at patients who receive liso-cel on the experimental arm, meaning the second line setting, and patients who receive liso-cel as a function of the crossover in third line. And here we have a two-year follow-up. The two-year overall survival for patients who receive liso-cel in second line was 95%. And the two-year overall survival for patients who receive liso-cel in third line was 78%, which underscores the fact that giving liso-cel earlier when needed in patients with high-risk second-line large B-cell lymphoma becomes quite crucial. There were no new safety signals seen, and overall there were seven deaths, two on the liso-cel arm and five on the standard of care arm. Four of the five on the standard of care was secondary to progression of disease. So thus, overall in net, TRANSFORM shows a very high progression-free survival, overall survival with liso-cel-treated patients, thus demonstrating the curative potential of liso-cel in this setting.

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