Second-line axi-cel improves EFS in elderly patients with R/R LBCL

Second-line treatment with the CAR* T-cell therapy axicabtagene ciloleucel (axi-cel) led to significantly longer event-free survival (EFS) in patients aged ≥65 years with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) compared with standard of care (SoC), according to a preplanned subgroup analysis of the ZUMA-7** trial presented at EHA 2022.

This study consisted of 109 patients aged ≥65 years (61 percent male) with LBCL who had a relapse within ≤12 months after first-line chemoimmunotherapy. Participants were randomized to receive either axi-cel (n=51) or SoC (n=58). SoC therapy consisted of 2–3 cycles of investigator-selected platinum-based chemoimmunotherapy and high-dose therapy with autologous stem-cell transplantation. The primary endpoint of the study was EFS, which was defined as the time from randomization to the earliest date of disease progression. [EHA 2022, abstract S211]

At a median follow-up of 24.3 months, patients treated with axi-cel achieved significantly longer median EFS compared with SoC (21.5 vs 2.5 months; hazard ratio [HR], 0.276; descriptive p<0.0001). These results were despite more patients in the axi-cel than SoC group having high-risk features at baseline, such as sAAIPI*** of 2–3, elevated lactate dehydrogenase level, and HGBL⁺ with or without MYC and BCL2 and/or BCL6 rearrangement.

The 24-month EFS rate was also higher among patients on axi-cel than those on SoC (47.8 percent vs 15.1 percent).

Axi-cel-treated patients also demonstrated a significantly higher objective response rate compared with SoC-treated patients (88.0 percent vs 52.0 percent; odds ratio, 8.81; descriptive p<0.0001), with a complete response (CR) rate of 75.0 percent vs 33.0 percent.

The median overall survival (OS) was prolonged in the axi-cel vs the SoC group (HR, 0.517; descriptive p=0.0175), despite more than half of the patients in the SoC group having received off-protocol subsequent cellular immunotherapy, noted lead author Dr Anna Sureda from the Department of Hematology at Institut Català d’Oncologia-Hospitalet in Barcelona, Spain.

The estimated 2-year OS rate was higher in the axi-cel group than the SoC group (64.0 percent vs 51.0 percent).

Grade ≥3 adverse events (AEs) occurred in 94.0 percent of the patients in the axi-cel group and 82.0 percent in the SoC group, with 51.0 and 42.0 percent of the patients, respectively, reporting serious AEs. Pyrexia, neutropenia, and nausea were the most common AEs reported in both treatment groups. “Axi-cel had a manageable safety profile that was consistent with previous studies and real-world data in patients of all ages,” said Sureda.

Treatment with axi-cel vs SoC showed a clinically meaningful improvement in quality of life (QoL) between baseline and day 100, as shown by changes in mean scores of EORTC QLQ-C30 global health status, EORTC QLQ-C30 physical functioning, and EQ-5D-5L VAS (descriptive p<0.0001, p=0.0019, and p<0.0001, respectively).

“[Axi-cel has been] approved for the treatment of adult patients with R/R LBCL after ≥2 lines of systemic therapy and most recently, in the US, for R/R LBCL within 12 months of first-line chemoimmunotherapy,” said Sureda.

“Axi-cel demonstrated superiority over second-line SoC in patients [aged] ≥65 years, despite the greater frequency of high-risk features in the axi-cel group, with >eightfold greater median EFS, >threefold greater estimated 24-month EFS rate, over double the CR rate, and almost three times the proportion of patients receiving definitive therapy,” she said.

“[As] age can be a determining factor in the decision to use curative therapy, … these data demonstrate that older patients, who are frequently considered transplant ineligible based on age, can safely receive second-line curative intent therapy,” noted Sureda.

“The superior clinical outcomes and patient experience with axi-cel over SoC should help inform treatment choices in second-line R/R LBCL for patients [aged] ≥65 years,” she added.

*CAR: Chimeric antigen receptor

**ZUMA-7: Efficacy of axicabtagene ciloleucel compared to standard of care therapy in subjects with relapsed/refractory diffuse large B-cell lymphoma

***sAAIPI: second-line Age-Adjusted International Prognostic Index

⁺HGBL: High-grade B-cell lymphoma