Expert Highlights Real-World Findings With Axi-Cel in DLBCL

January 21, 2019
Shannon Connelly

Brian T. Hill, MD, PhD, discusses real-world findings with axi-cel in patients with DLBCL and how these findings can be used to inform practice.

Brian T. Hill, MD, PhD

Since its approval in October 2017, axicabtagene ciloleucel (KTE-C19, axi-cel) has started to be used much more broadly for the treatment of patients with relapsed/refractory large B-cell lymphoma (DLBCL).

In data presented during the 2018 ASH Annual Meeting, safety and efficacy findings was found to be similar in patients treated with the chimeric antigen receptor (CAR) T-cell therapy in a real-world setting, compared with patients treated on the ZUMA-1 trial, which led to the FDA approval.

Seventeen academic centers in the United States contributed data for the retrospective real-world study. According to the findings, among 112 evaluable patients infused with axi-cel on this study, the overall response rate (ORR) was 79% and the complete response (CR) rate was 50% at day 30. This compares with an 82% best ORR and a 58% CR rate among 108 patients treated on the ZUMA-1 trial.

Additionally, many of the patients included in the real-world study would not have been eligible for inclusion in the ZUMA-1 trial. Criteria that would have excluded them from ZUMA-1 included ECOG performance status >1 (n = 22), platelets <75k (n = 17), GFR <60 (n = 12), active DVT/PE (n = 13), liver enzyme abnormalities (n = 10), a history of CNS lymphoma (n = 8), recent checkpoint inhibitor therapy (n = 7), ejection fraction <50% (n = 4), prior CD19 CAR T therapy (n = 4), and prior allogeneic transplant (n = 2).

“I think this kind of validates the approach that many centers are taking, to use axicabtagene ciloleucel in a broader, older, sicker patient population, which is really what we see in the real-world setting,” said Brian T. Hill, MD, PhD.

In an interview withTargeted Oncology, Hill, a physician in the Department of Hematology and Medical Oncology at the Cleveland Clinic, discussed the data from the real-world study with axi-cel and how these findings can be used to inform practice.

TARGETED ONCOLOGY: Can you provide some background on this retrospective study?

Hill:This study was a report from a number of investigators from large academic centers that are involved in CAR T-cell therapy for [patients with] DLBCL. We have had an FDA-approved drug now for a little more than a year for large B-cell lymphoma. That is axi-cel. It was approved in October of 2017 and since then it has been increasingly used in what we call a commercial or real-world setting. In the registration trial that led to the approval of the drug, there were a number of inclusion/exclusion criteria that restricted patients to be enrolled on the study and treated with axi-cel. Since the drug has been approved and is commercially available, it is now being used much more broadly. The study is what we call a real-world experience or a retrospective analysis from multiple centers across the United States that have been using the therapy.

What the study showed, which is interesting, is that about half of the patients in the real world who receive axi-cel would not have been eligible for the clinical trial called ZUMA-1, which is the registration trial for axi-cel. Patients had higher comorbidities, platelet counts were low, they had other reasons why they wouldn't have been able to receive this on a clinical trial. Despite this, we find that the response rates and the safety seem pretty comparable to what we saw in the clinical trial. I think this kind of validates the approach that many centers are taking to use axi-cel in a broader, older, sicker patient population, which is really what we see in the real-world setting.

TARGETED ONCOLOGY: What is important to highlight about these data?

Hill:In addition to the efficacy—the CR rate around 40% and ORR higher than that—what we see even with the relatively short follow-up on the study is that the safety in terms of cytokine release syndrome and encephalopathy is actually pretty comparable to what was originally seen. So even though these patients are somewhat older, have poor performance status, and are generally sicker, it's still a safe treatment to deliver.

TARGETED ONCOLOGY: Why are these findings important?

Hill:I think what's interesting is this study in a relatively short period of time was able to accumulate data on about 300 patients, which is 3 times more than the number of patients treated on the original study. I think what we can find is that when groups work together collaboratively, they can rapidly generate data that inform practice in the real world, which is at the end of the day what we really want to do: help our patients. I think it broadens our knowledge base significantly.


Nastoupil LJ, Jain MD, Spiegel JY, et al. Axicabtagene ciloleucel (Axi-cel) CD19 chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory large b-cell lymphoma: real world experience. In: proceedings from the 2018 ASH Annual Meeting; December 1-4, 2018; San Diego, CA. Abstract 91.