Axi-Cel’s QOL Gains in R/R LBCL Extend to Transplant-Ineligible Patients

An exploratory analysis of the phase 2 ALYCANTE trial (NCT04531046) reveals that patients with relapsed/refractory large B-cell lymphoma (LBCL) experience significant improvements in health-related quality of life (HRQOL) when treated with axicabtagene ciloleucel (Yescarta; axi-cel) as second-line treatment, regardless of transplant eligibility.¹

In the ALYCANTE trial, patients who were ineligible for autologous stem cell transplantation (ASCT) were treated with a single infusion of the chimeric antigen receptor (CAR) T-cell therapy. According to the new findings published in Blood Advances, there was an initial deterioration in HRQOL scores at 1 month postinfusion in physical, role, social functioning, and fatigue, which recovered by 3 months and remained stable or continued to improve by 12 months.

Importantly, the HRQOL improvements were found to be similar to, or in some cases better than, those seen in transplant-eligible patients treated with axi-cel in the phase 3 ZUMA-7 trial (NCT03391466). By 3 months after infusion, patients’ overall health status and fatigue levels had improved to match those typically reported by people of a similar age in the general population.

In April 2022, the FDA approved axi-cel as a second-line treatment for adult patients with LBCL who have relapsed within 12 months or are refractory following first-line chemoimmunotherapy.² This approval came after data from the ZUMA-7 trial showed that axi-cel significantly prolonged event-free survival relative to standard chemoimmunotherapy, high-dose therapy, and ASCT (HR, 0.40; 95% CI, 0.31-0.51; stratified P <.0001).³

Of note, axi-cel’s prescribing information contains a boxed warning for cytokine release syndrome (CRS) and neurologic toxicities. These new data provide a necessary framework for counseling patients who may be hesitant to undergo intensive CAR T-cell therapy due to concerns about functional decline. The study suggests that while the initial month of treatment may be strenuous, the long-term recovery leads to a quality of life that often exceeds their pretreatment state.

“Overall, the findings of this analysis highlight the consistent and meaningful impact of axi-cel on HRQOL irrespective of transplant eligibility,” Charton et al, study authors, wrote in the publication.¹ “Confirmation of these results in other countries should be performed to allow generalization of these results. These results further support the use of axi-cel as a second-line therapy for ASCT-ineligible patients with relapsed/refractory LBCL, expanding the applicability of CAR T-cell therapies across a broader patient population.”

About the ALYCANTE Trial

Expanding on the ZUMA-7 trial, ALYCANTE was a multicenter, open-label phase 2 study conducted in France and Belgium that evaluated axi-cel as second-line treatment for a different patient population with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma.⁴ The study enrolled 62 adult patients, specifically targeting those deemed ineligible for ASCT due to age, comorbidity, or prior ASCT. The median age of the cohort was 70 years (range, 49-81), reflecting the "real-world" nature of the transplant-ineligible population.

The primary end point of the main study was the complete metabolic response (CMR) rate at 3 months after axi-cel infusion, which was met with a 3-month CMR rate of 71.0% (95% CI, 58.1%-81.8%).⁵ The safety profile of axi-cel in the study was in line with expected toxicities, and grade 3 to grade 4 events of CRS and neurologic events occurred in 8.1% and 14.5% of patients, respectively.

The present analysis of HRQOL, an exploratory end point, utilized 2 validated instruments for measurement: the EORTC Quality of Life Questionnaire (EORTC QLQ-C30) and the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire.

REFERENCES

1. Charton E, Anota A, Bachy E, et al. Health-related quality of life after second-line axi-cel in transplant-ineligible patients with large B-cell lymphoma. Blood Advances. 2026;10(5):1773-1782. doi:10.1182/bloodadvances.2025018057

2. FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma. News release. United States Food and Drug Administration. April 1, 2022. Accessed March 24, 2026. https://tinyurl.com/4htsvpz7

3. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386(7):640-654. doi:10.1056/NEJMoa2116133

4. Axi-cel as a 2nd line therapy in patients with relapsed/refractory aggressive B lymphoma ineligible to autologous stem cell transplantation. ClinicalTrials.gov. Updated October 9, 2024. Accessed March 23, 2026. https://clinicaltrials.gov/study/NCT04531046

5. Houot R, Bachy E, Cartron G, et al. Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: a phase 2 trial. Nat Med. 2023;29(10):2593-2601. doi:10.1038/s41591-023-02572-5