Transcript
My name is Peter Riedell. I'm an assistant professor at the University of Chicago. Today, I'll be discussing a multicenter retrospective analysis of outcomes and toxicities with commercial axicabtagene ciloleucel and tisagenlecleucel for relapsed and refractory aggressive B-cell lymphomas.
I'm presenting this study on behalf of my colleagues of the CAR T-cell Consortium. This study essentially looked at outcomes of patients who received CAR T-cell therapy for aggressive large B-cell lymphoma in the commercial setting.
All centers that were involved in this project had the ability to prescribe either axicabtagene ciloleucel, or axi-cel, or tisagenlecleucel, also known as tisa-cel, as of May of 2018, which was the point in time at which tisagenlecleucel was approved for aggressive B-cell non-Hodgkin's lymphoma by the US FDA.
The basis of the abstract was to look at practice patterns, efficacy, toxicity, along with resource utilization metrics. For this study, data collection included all patients who underwent apheresis, with the intention to manufacture CAR T-cells.
Within this study, patient selection, toxicity management, disease assessment all followed institutional practices. The data cutoff for the analyses was January 15th of 2020.
Each center essentially did a retrospective chart review to abstract a number of clinical variables, including efficacy data, along with toxicity and resource utilization.
In terms of the results of the study, we looked at the baseline patient characteristics. It does appear that there was a slightly different patient population that received each of these FDA-approved products. Patients who received tisa-cel, on average, were older, with a median age of 67 compared to 59 years of age in those that received commercial axi-cel.
Additionally, there was a higher percentage of older adults receiving the tisa-cel product at 62% of the population age 65 or greater compared to only 34% of the patients receiving axi-cel were age 65 or older.
Additionally, those patients that received axi-cel were more likely to have primary refractory disease, where we saw 45% of the population have primary refractory disease in those that received axi-cel compared to only 18% of those patients that received tisa-cel.
Additionally, it appears that those that received tisa-cel were also more heavily pretreated. Approximately 86% of the patients receiving tisa-cel received 3 or more prior lines of therapy compared to only 73% of patients that received axi-cel therapy.
Additionally, the vein-to-vein time was longer in patients who received tisa-cel therapy at 44 days compared to 28 days for those that received axi-cel. We believe this also impacted the utilization of bridging therapies within this retrospective study.
As can be seen in the slide, bridging therapy was more frequently incorporated into the treatment of those who received tisa-cel, whereby 75% of the patients received bridging therapy compared to only 61% of those patients received bridging therapy that were treated with axi-cel.
Throughout the study, we were also able to look at toxicity patterns. Initially, each of the sites graded toxicity per their institutional practices. Also, as part of this study, we made efforts to harmonize the toxicity grading scale to the recently adopted ASTCT consensus grading criteria in order to compare toxicities among sites on a more uniform playing field.
Based on the readout from our study, it appears that the toxicity seen with patients treated with tisa-cel was lower, both in terms of all grades of cytokine release syndrome, along with particularly those more serious grades of CRS.
A similar pattern was seen in relation to neurologic toxicity, where patients treated with tisa-cel appeared to have lower incidence of all grades, along with serious grades of neurologic toxicity.
Throughout the study, we're also able to look at toxicity management, particularly tocilizumab and corticosteroid use. Those patients receiving axi-cel, on average, had incidence of receiving more tocilizumab in terms of both median doses and utilization in general.
Additionally, those patients that received axi-cel did have higher utilization of corticosteroids at 53% of that population requiring corticosteroids compared to only 8% of the patients treated with tisa-cel. Additionally, there was a higher utilization of other anticytokine therapies such as siltuximab in those patients treated with axi-cel compared to tisa-cel.
In terms of efficacy, we were able to look at response rates in the patients that received each of these therapies. Also, we're able to, for reference, compare those responses to the results of the pivotal ZUMA-1 and JULIET trial.
Patients treated with axi-cel within the context of this study had a day 90 overall response rate of 64% compared to 51% in those patients treated with tisa-cel. The day 90 complete remission rate was 53% in patients treated with axi-cel compared to 42%in patients treated with tisa-cel. As can be seen, these rates are relatively in line with those noted in the pivotal clinical trials.
We also were able to look at progression-free survival in patients treated with each of these products. With a median follow-up of 7.6 months in those patients treated with axicabtagene ciloleucel, the median progression-free survival was 6.7 months.
In patients treated with tisagenlecleucel with the median follow-up of 6.2 months, the median progression-free survival was 3.2 months within the context of our study.
Additionally, in terms of more resource utilization metrics, we were able to look at inpatient administration of each of these therapies. It appeared that axi-cel was more frequently utilized in the inpatient setting in 92% of patients compared to only 37% of patients receiving tisa-cel were treated on an inpatient basis.
Similarly, there was a higher number of days hospitalized within the first 28 days in those treated with axi-cel at 16 days compared to 2 days in patients treated with tisa-cel. There was also a higher utilization of advanced supportive care measures such as ICU in patients treated with axi-cel at 39% compared to 7% in patients treated with tisa-cel.
In conclusion, we found that tisa-cel recipients were more likely to be of older age, more heavily pretreated, and also to receive bridging therapy while their CAR T-cell product was being manufactured. Tisa-cel appeared to be associated with a lower incidence and severity of both cytokine release syndrome and neurologic toxicity.
Within the context of our study, we showed that efficacy outcomes in the commercial setting appeared relatively similar to those presented in the pivotal clinical trials, although it should be noted that propensity score matching will be needed to more adequately compare efficacy outcomes among the commercial products.
Axi-cel was associated with a longer hospital length of stay, an increased incidence of ICU transfer, and a greater utilization of anticytokine therapies such as tocilizumab and corticosteroids.
Moving further, we will continue these efforts by accruing a larger patient cohort in order to better characterize the long-term clinical activity, safety profile, along with patterns of use of these cellular therapies in the commercial setting. Thank you.
