Second-Line Axi-Cel Is Efficacious, Safe in Real-World Patients With R/R LBCL

Dasom (Caroline) Lee, MD

Treatment with axicabtagene ciloleucel (axi-cel; Yescarta) demonstrated similar early efficacy as second-line therapy in real-world patients with relapsed/refractory large B-cell lymphoma (LBCL) compared with outcomes for patients treated with the CAR T-cell therapy during the phase 3 ZUMA-7 trial (NCT03391466), according to Dasom (Caroline) Lee, MD.¹

Lee highlighted key findings from a real-world analysis evaluating second-line axi-cel in patients with relapsed/refractory LBCL at the 2024 ASH Annual Meeting. In April 2022, the FDA approved axi-cel for the treatment of adult patients with LBCL that is refractory to first-line chemoimmunotherapy or relapses within 12 months of receiving chemoimmunotherapy.²

Findings from the real-world study showed that at a median follow-up of 12.0 months (95% CI, 11.5-12.1), all eligible patients (n = 436) experienced an objective response rate (ORR) of 79% and a complete response rate of 64%.¹ Notably, the ORR was 79% for patients who would have been eligible for ZUMA-7 or had unknown eligibility (n = 213); and for patients who would have been ineligible for the phase 3 study (n = 210).

The 12-month event-free survival (EFS) rate for all patients in the real-world study was 53% (95% CI, 48%-58%), and the 12-month overall survival (OS) rate was 71% (95% CI, 56%-76%).

Any-grade cytokine release syndrome (CRS) occurred in 87% of patients; however, grade 3 or higher CRS was reported in 5% of patients. The rates of any-grade and grade 3 or higher immune effector cell–associated neurotoxicity syndrome (ICANS) were 50% and 22%, respectively.

In an interview with OncLive^®, Lee discussed the rationale behind the real-world analysis of second-line axi-cel, how to navigate challenges of evaluating outcomes in this patient population, and the use of axi-cel in the broader clinical setting.

Lee is a fellow in the Division of Hematology at Stanford University in Palo Alto, California.

OncLive: What was the rationale for conducting the real-world analysis of second-line axi-cel in patients with relapsed/refractory LBCL?

Lee: The ZUMA-7 trialwas very impressive, and its [data] led to the approval of [axi-cel as] second-line therapy in the LBCL setting. [Axi-cel generated] had an OS benefit [vs standard-of-care chemoimmunotherapy] at 5 years of follow-up.

However, whether [axi-cel] is well tolerated and has the same efficacy is [generally] unknown in the real-world setting. That was the motivation for our study. This is particularly important because this patient population is so diverse; therefore, we want to characterize which patients are doing well and which patients are not, and then we can share that information with our patient population.

How did this real-world population compare with the population enrolled in ZUMA-7?

From our study, we learned that [approximately] half of the [real-world] patients [52%] would have been ineligible for ZUMA-7, and the major factors leading to ineligibility were organ impairment [34%] and prior malignancies [16%]. That was very helpful in determining how we interacted with or treated patients because that would give us an understanding of what we should expect when treating the patients, given their [baseline] characteristics.

What were the key findings from the real-world study presented at the 2024 ASH Annual Meeting?

We included 446 patients [in the analysis] with a median follow-up of 12.0 months. We found that 52% of patients would have been ineligible for the ZUMA-7 trial. Most importantly, we demonstrated similar [real-world] effectiveness [with axi-cel compared with data from] ZUMA-7, including for EFS and OS, as well as the safety profile, including the [the rates of] CRS and ICANS. These are encouraging data for our patient population getting second-line therapy.

How do the safety results influence best practices for toxicity management in the real-world setting?

We found that the toxicity profile, including [rates of] CRS or ICANS, was similar to [the short-term follow-up] from the ZUMA-7 trial. We will do longer follow-up to confirm those findings.

We do know that there [was a higher incidence of] non-relapse mortality at 6 months for patients [who would have been] ineligible for ZUMA-7. Therefore, with longer follow-up, we can confirm these findings and find out what causes are driving this non-relapse mortality. Then, we can work on preventing those complications for this patient population.

How do these findings support the use of axi-cel in a broader clinical setting? What implications do the data have for patient selection?

When looking at the baseline characteristics, we had an older patient population [in the real-world study], given that we have transitioned from third line beyond or second-line therapy. Also, we have learned there are a lot of patients with comorbidities as well, given the older age. So learning more about the risk stratification of these patients and how that will affect the outcomes, will be very helpful, and that will be something that we’d like to do with a deeper analysis with long-term follow-up.

References

1. Lee DC, Kambhampati S, Odstricil-Bobillo MS, et al. Real-world early outcomes of second-line axicabtagene ciloleucel (axi-cel) therapy in patients (pts) with relapsed or refractory (R/R) large B-cell lymphoma (LBCL). Blood. 2024;144(supp 1):526. doi:10.1182/blood-2024-199139
2. FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma. FDA. April 1, 2022. Accessed January 3, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-axicabtagene-ciloleucel-second-line-treatment-large-b-cell-lymphoma