ALYCANTE- AXI-CEL IN LYMPHOMA CAR T ELIGIBLE BUT NON-TRANSPLANT ELIGIBLE

Investigators from the Lymphoma Study Association (Lysa) have published the results from the ALYCANTE study in Nature Medicine: https://www.nature.com/articles/s41591-023-02572-5

Background

Previously in the ZUMA-7 study, Axicabtagene ciloleucel (axi-cel) demonstrated superior efficacy compared to standard of care as second-line therapy in patients with high-risk relapsed/refractory large B cell lymphoma considered eligible for autologous stem cell transplantation (ASCT)¹; however, in clinical practice, roughly half of patients with R/R LBCL are deemed unsuitable candidates for ASCT²

ALYCANTE, an open-label, phase 2 study, evaluated axi-cel as a second-line therapy in 62 patients with R/R LBCL who were considered ineligible for ASCT. The primary end point was investigator-assessed complete metabolic response at 3 months from axi-cel infusion. Key secondary end points included progression-free survival, overall survival and safety.

Results:

The study met its primary end point with a complete metabolic response of 71.0% (95% confidence interval, 58.1–81.8%) at 3 months. With a median follow-up of 12.0 months (range, 2.1–17.9), median progression-free survival was 11.8 months (95% confidence interval, 8.4–not reached) and overall survival was not reached. 52 patients (83.9%) received bridging therapy between study enrollment and axi-cel infusion. At 3 months from the axi-cel infusion, the investigator-assessed ORR was 75.8% (95% CI, 63.3–85.8%).In total, 37 patients (59.7%) remained in CMR, as assessed by the investigator, at 6 months from the axi-cel infusion (95% CI, 46.5–72.0%).

The investigator-assessed best ORR and best CMR were 90.3% and 79.0%, respectively.

When assessed by a central review panel, CMR and ORR at 3 months were 66.1% (95% CI, 53.0–77.7%) and 69.4% (95% CI, 56.4–80.4%), respectively. The best ORR and best CMR as assessed by the central review panel were 91.9% and 82.3%, respectively3.

There was no unexpected toxicity. Grade 3–4 cytokine release syndrome and neurologic events occurred in 8.1% and 14.5% of patients, respectively.

The investigators conclude that these results support axi-cel as second-line therapy in patients with R/R LBCL ineligible for HDCT/ASCT.Yescarta is indicated for the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL)and high-grade B-cell lymphoma (HGBL) that relapses within 12 months from completion of, or isrefractory to, first-line chemoimmunotherapy.

Yescartais indicated for the treatment of adult patients with relapsed or refractory (r/r) diffuse largeB-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL), after two ormore lines of systemic therapy. Limitation of Use: Yescarta is not indicated for the treatment of patients with primary or secondary. central nervous system lymphoma.

Yescarta is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy.

For further informationandfull list of adverse events, please refer to the approved prescribinginformation asavailableatIsraeliMinistryofHealthwebsite:

https://israeldrugs.health.gov.il/#!/byDrug

Any suspected adverse events should be reported to the Ministry of Health according to the National Regulationbyusing an online form athttps://sideeffects.health.gov.il/

Additionally, adverse events can be reported to Gilead:Safety_FC@gilead.com

This article is intended for healthcare providers only.

For any further questions please contact: medinfo.israel@gilead.com

© Gilead Sciences Israel Ltd. All rights reserved

IL-YES-0130, NOV2023

1. Locke FL, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. Engl. J. Med. 2022;386:640–654. doi: 10.1056/NEJMoa2116133
2. Sehn LH, Salles G. Diffuse large B-cell lymphoma. Engl. J. Med. 2021;384:842–858. doi: 10.1056/NEJMra2027612.
3. Houot 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: 1038/s41591-023-02572-5