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ASH 2021 | Impact of age and co-morbidities on axi-cel efficacy

Frederick Locke, MD, Moffitt Cancer Center, Tampa, FL, discusses the impact of age and co-morbidities on the efficacy of axicabtagene ciloleucel (axi-cel), an autologous anti‑CD19 chimeric antigen receptor (CAR) T-cell therapy. 1343 patients treated with standard-of-care axi-cel, including ones who were ineligible to participate in the ZUMA-1 trial (NCT02348216) due to co-morbidities, were assessed. Patients over 65 years old or with co-morbidities had outcomes similar to younger patients without co-morbidities. However, patients over 65 years old had increased rates of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.

Transcript (edited for clarity)

Very excited to be presenting abstract 530, which is our real-world outcomes with axicabtagene ciloleucel or axi-cel for the treatment of large B-cell lymphoma. We know axi-cel is an autologous anti-CD19 CAR-T cell therapy. It’s approved for use in the third or later line treatment of a large B-cell lymphoma. And that’s based upon the ZUMA-1 clinical trial, the pivotal ZUMA-1 trial that led to those approvals...

Very excited to be presenting abstract 530, which is our real-world outcomes with axicabtagene ciloleucel or axi-cel for the treatment of large B-cell lymphoma. We know axi-cel is an autologous anti-CD19 CAR-T cell therapy. It’s approved for use in the third or later line treatment of a large B-cell lymphoma. And that’s based upon the ZUMA-1 clinical trial, the pivotal ZUMA-1 trial that led to those approvals. Now we know in the real world setting patients are being treated with axi-cel who have comorbidities that would’ve made them ineligible for treatment on ZUMA-1. And in fact, real world safety and efficacy results of axi-cel are out.

And it suggests that those patients can still benefit from axi-cel although the response rates and duration of response are more advantageous for patients who would’ve been eligible for ZUMA-1. So here in this study, we interrogated the axi-cel post-approval safety study, which is being conducted by the CIBMTR to assess the impact of age and comorbidities in the real-world setting. And in this study, 1500 patients were enrolled and here we’re presenting data on 1343 patients. And these were the patients that had at least 180 days follow up.

Importantly, 38% of these patients were 65 years of age or older. A small percentage, 4% had an ECOG performance status of two or greater. But overall 51% of the patients would not have been eligible for ZUMA-1 either because of elevated performance status or some comorbidity or CNS lymphoma being present. And so over half the patients in the real world are being treated who would not have been eligible for the pivotal ZUMA-1 study.

When we look at the objective response rate in these patients, 73.6% had a response and 56% of patients had a complete response. So very comparable to the pivotal ZUMA-1 data, and then, and the, with a median follow up of 13 months, median progression-free survival was 8.8 months. Median overall survival was 22.4 months. So despite these patients having comorbidities and over half, not having been eligible for the ZUMA-1 trial, we’re seeing similar progression-free survival and overall survival rates, which is very important. We look at the toxicity, cytokine release syndrome was seen in over 80% of patients, but grade three or higher severe cytokine release syndrome was seen in 8% of patients. Similarly, neurotoxicity, or ICANS reported in 55% of patients with grade three or higher ICANS in 25% of patients.

Now, when we looked at outcomes by some of the variables, advanced age, greater than equal to 65, didn’t impact efficacy outcomes. Patients had similar efficacy outcomes. Actually perhaps better efficacy outcomes. However, older patients had higher rates of CRS and ICANS. Patients with coexisting organ dysfunction had generally favorable outcomes of axi-cel, but the presence of moderate to severe hepatic, renal and cardiac diseases were associated with lower overall survival. And so really it’s an important study with a huge number of patients confirming that axi-cel can really have great efficacy outcomes in patients with relapse/refractory large B-cell lymphoma.

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