The 2022 Tandem Meetings | Interim analysis of TRANSFORM: liso-cel vs SOC in high-risk R/R LBCL

So, hi everyone. My name’s Manali Kamdar, University of Colorado Cancer Center. I had the pleasure on behalf of my co-authors to present the interim results from the randomized Phase III transform study, a study that compared lisocabtagene maraleucel, which is a CD19-directed CAR-T therapy versus the current standard of care, which is salvage chemotherapy followed by autologous stem cell transplantation in patients with high-risk relapsed or refractory large B-cell lymphoma. So just as a way of background patients whose large cell lymphoma relapses within 12 months, or is primary refractory to frontline chemoimmunotherapy, these patients have exceptionally poor outcomes. And for decades, salvage immunochemotherapy followed by high dose chemotherapy and stem cell transplantation has been the standard of care.

Unfortunately, though, only about a quarter of transplant intended patients are able to achieve durable remission. So with that in mind, the Phase III TRANSFORM study was designed, which was a head to head comparison of liso-cel versus standard of care. Patients between the age groups of 18 and 75 with this high-risk relapsed/refractory large cell lymphoma, as well as other subtypes, such as follicular grade IIIB as well as other transformed lymphomas were included. Patients underwent screening leukophoresis followed by a 1:1 randomization to either getting liso-cel or salvage chemotherapy, which was three cycles followed by high dose chemotherapy and transplant. Patients on the liso-cel arm were able to get one cycle of salvage chemotherapy as bridging while they awaited cell manufacturing. The primary endpoint of this study was event-free survival and the key secondary endpoint were complete response rate progression-free survival, overall survival, as well as patient-reported outcomes.

And at this point in the form of pre-specified interim analysis at a median follow up of 6.2 months, liso-cel demonstrated superior efficacy compared with standard of care, it met its primary endpoint, which was event-free survival with lysis cell arm having a median EFS of 10.1 months, standard of care having median EFS of 2.3 months, that translated into a hazard ratio of 0.349, which amounted to 65% risk reduction in favor of the liso-cel arm. Key secondary endpoint of complete response rate progression-free survival were also statistically significant and higher on the liso-cel arm risk compared to standard of care. The complete response rate was 66% on liso-cel versus 39% on standard of care. And the median PFS was 14.8 months versus 5.7 months on the liso-cel arm versus standard of care respectively. Extremely interestingly, and also very impressive to note that despite this being an interim analysis and despite the fact that it allowed for crossover at a median follow up of 6.2 months, the overall survival looks like maybe trending towards liso-cel. The Kaplan-Meier curves have clearly split. So we do await long term data with the primary analysis results to see if this difference will continue and translate into a statistically significant benefit. In terms of safety profile, liso-cel showed very manageable safety with extremely low rates of severe CRS and neurological events. Overall, it is important to note that there was no grade 4 or grade 5 cytokine release syndrome or neurological events that were reported on this study. In fact, with regards to grade 3 CRS, only one patient had grade 3 CRS and only 4% of patients had grade 3 neurological events.

So overall in conclusion, compared with the standard of care, liso-cel demonstrated a highly statistically significant and clinically meaningful improvement in the following primary, as well as key secondary endpoints, which was reduced risk of PFS events by 65% achieved a 27% higher complete response rate and reduced risk of PFS events by 59%. There was no grade 4 or grade 5 cytokine release or neurological events that were reported. So based on this result on the transform study, liso-cel did show superiority over the current standard of care, which is salvage chemo followed by an autologous stem cell transplant in this high-risk relapsed/refractory DLBCL patients. And thus it does represent a potential new second line treatment option for patients with relapsed/refractory large B-cell lymphoma.