Real-World Safety, Efficacy, and Utilization of Axicabtagene Ciloleucel and Tisagenlecleucel for B-Cell Lymphomas

Peter Riedell, MD, Section of Hematology/Oncology, University of Chicago, Chicago, IL, discusses findings from a study which assessed safety, patterns of use, resource utilization, and efficacy with commercial axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) for the treatment of relapsed/refractory B-cell lymphomas.

These findings were presented at the 2021 ASH Annual Meeting.

Transcript: 

My name is Peter Riedell from the University of Chicago. Today, I'll be discussing a study that was presented at the most recent ASH Congress. It's a multicenter analysis of outcomes, toxicities, and patterns of use with commercial axicabtagene ciloleucel and tisagenlecleucel for relapsed/refractory aggressive B-cell lymphomas.

In our stud, what we aimed to really delineate was some of the efficacy, safety, patterns of use and resource utilization in centers that particularly have the option of prescribing either commercially available axi-cel or tisa-cel for patients with relapsed and refractory aggressive B-cell non-Hodgkin's lymphoma.

This was a retrospective analysis encompassing seven US academic medical centers. For the purposes of this study, data collection included all patients who underwent apheresis with the intention to manufacture CAR T-cell therapy starting in May 2018, which is a point in time when each of the centers have the option of prescribing either of these products, through the July 31, 2019.

Within this study, things like patient selection, toxicity management, and disease assessments each followed institutional practices. This is an update of our data, including a data cuts of the December 31, 2020.

If we dive into the data a little bit, we did notice that there were some unique differences between the baseline patient characteristics and those recipients of the axi-cel product compared to tisa-cel.

Particularly, we noted that axi-cel recipients were older age, having both a higher median age, and a higher percentage of patients receiving tisa-cel were advanced age, age 65 years of age and older, compared to those receiving axi-cel.

Additionally, one of the other unique things that we noted was that axi-cel recipients were more likely to have primary refractory disease compared to those that received the tisa-cel product.

Other things of note, axi-cel patients were actually less heavily pretreated, in our study. The recipients of tisa-cel, there was a higher percentage of those that have received three or more prior lines of therapy compared to axi-cel patients.

Additionally, we noted that the turnaround time or the vein-to-vein time from collection of the patient's T-cells to essentially shipping the product back and infusion was longer in tisa-cel recipients at 44 days compared to 28 days in those that received axi-cel.

We were also able to look at some of the baseline patient characteristics and look at their eligibility for the pivotal clinical trials. We noted that between 40% and 60% of patients treated within our study would have actually been ineligible for the pivotal trial including ZUMA-1 for those that received axi-cel and JULIET trial for those that received tisa-cel.

We were also able to look at safety. In this study, we regraded each of the patient's toxicity based on the ASTCT consensus grading. We were able to see that there was a higher incidence of any grade cytokine release syndrome in patients that received axi-cel compared to tisa-cel.

Additionally, tisa-cel did appear to be associated with a lower incidence along with severity of neurologic toxicity compared to recipients of axi-cel.

We also looked at specifics in terms of toxicity managements. In particular, we were able to see that there was a higher application of tocilizumab, corticosteroids, and soltoxicimab in recipients of axi-cel compared to tisa-cel.

In terms of efficacy analysis, with a median follow up exceeding 12 months in both populations, we actually were able to find similar rates in terms of overall response rates and complete response rates between the different treatment groups.

Furthermore, this translated into a similar unadjusted 12-month progression-free survival and overall survival between patients that received axi-cel and those that received tisa-cel.

One of the other unique aspects of our study is looking at some resource utilization metrics, and we were able to find that those that received tisa-cel were more commonly receiving their therapy in the outpatient setting, which was seen in 62% of recipients of tisa-cel compared to axi-cel, which was only provided in the outpatient setting in 8% of patients in that treatment group.

Additionally, there was a longer median length of stay among hospitalized patients in the axi-cel group compared to tisa-cel, and also a higher utilization of ICU and a higher incidence of ICU transfer in axi-cel patients compared to tisa-cel.

In conclusion, some of the things that we found in our studies is that there are certainly differences in the baseline patient characteristics between those that were in the axi-cel treatment group compared to tisa-cel. In particular, tisa-cel recipients were more likely to be older, more heavily pretreated, and less likely to have primary refractory disease.

It was interesting to note that safety did appear comparable and favorable to the pivotal clinical trials when utilized in the commercial setting.

There were some differences in terms of resource utilization between the two different groups where the axi-cel patients did have a higher utilization of anti-cytokine therapy, a higher incidence of ICU transfer, and a longer median hospital length of stay among those that were hospitalized.

Encouragingly, we did see similar rates of response, including overall response rates, progression-free survival, and overall survival between the two groups, although this wasn't really matched based on baseline patient characteristics, and therefore, we do need to delve a little bit further into that to better understand some of the outcomes in specific patient subsets.

In general, our study does help to better understand practice patterns and provide some highlights and insights into patient selection resource utilization in recipients of these two commercial products. Potentially, we hope that this information does inform patient selection for future CAR T-cell recipients.