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4505 Health-Related Quality of Life after Axi-Cel As a Second-Line Therapy in Patients with High-Risk Relapsed/Refractory Large B-Cell Lymphoma Who Are Ineligible for Autologous Stem Cell Transplantation: Results of the Alycante Phase II Trial

Program: Oral and Poster Abstracts
Session: 628. Aggressive Lymphomas: Cellular Therapies: Poster III
Hematology Disease Topics & Pathways:
Lymphomas, Diseases, Aggressive lymphoma, Lymphoid Malignancies
Monday, December 9, 2024, 6:00 PM-8:00 PM

Emilie Charton1*, Amelie Anota1*, Emmanuel Bachy, MD, PhD2, Guillaume Cartron, MD, PhD3*, François-Xavier Gros, MD4*, Franck Morschhauser, MD, PhD5, Lucie Oberic, MD6*, Thomas Gastinne, MD7*, Pierre Feugier, MD, PhD8*, Remy Dulery, MD, PhD9*, Catherine Thieblemont, MD10, Magalie Joris, MD11*, Fabrice Jardin, MD, PhD12*, Sylvain Choquet, MD13*, Olivier Casasnovas, MD14*, Gabriel Brisou, MD, PhD15*, Morgane Cheminant, MD, PhD16*, Jacques-Olivier Bay, MD, PhD17*, Francesco Llamas Gutierrez, MD18*, Cédric Portugues19*, Emmanuel Itti, MD, PhD20*, Xavier Pallard, MD, PhD21*, Paul Blanc-Durand22*, Yassine Al Tabaa, MD, PhD, PharmD23*, Clément Bailly, MD, PhD24*, Camille Laurent, MD, PhD25*, Francois Lemonnier26* and Roch Houot, MD, PhD27*

1Centre Léon Bérard, Lyon, FRA
2Lyon Sud Hospital, Lyon, France
3Centre Hospitalier Universitaire de Montpellier, Montpellier, France
4Hematology Department, Bordeaux University Hospital, Pessac, France
5Centre Hospitalier Régional Universitaire de Lille, Lille, France
6IUCT - Oncopole, Hematology Department, Toulouse, France
7Centre Hospitalier Universitaire de Nantes, Nantes, France
8CHU Brabois - Service d'Hématologie - Université Henri Poincaré, Nancy, France
9Clinical Hematology and Cellular Therapy, Sorbonne University, Saint-Antoine Hospital, Assistance Publique - Hôpitaux de Paris, INSERM UMRs 938, Paris, Île-de-France, France
10Hospital Saint-Louis, Paris, France
11Service d’Hématologie Clinique, Centre Hospitalier Universitaire Amiens-Picardie, Amiens, France
12INSERM U1245, Cancer and Brain Genomics, Centre Henri Becquerel, University of Rouen, Rouen, France
13Pitie-Salpetriere Hospital, Paris, France
14François Mitterand Hospital, Dijon, FRA
15Institut Paoli-Calmettes, Marseille, France
16Hopital Necker - Enfants Malades, AP-HP, Department of Hematology, Paris, France
17CHU ESTAING, Clermont-Ferrand, France
18Department of Pathology, CHU Pontchaillou, Rennes, France
19LYSARC, LYON, France
20Nuclear medicine department, Henri Mondor University Hospital, AP-HP, Créteil, FRA
21Centre Eugene Marquis, Rennes, France
22CHU Henri Mondor, Creteil, FRA
23Scintidoc Nuclear Medicine Center, Montpellier, France
24CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France
25Pathology Department, Institut Universitaire du Cancer , Oncopole, Toulouse, France
26Department of Hematology, Henri Mondor Hospital, CRETEIL, France
27Rennes university hospital - Hospital Pontchaillou, Rennes, France

Introduction: The ALYCANTE phase II trial, a LYSA study (ClinicalTrials.gov number NCT04531046), aimed to evaluate the investigator-assessed complete metabolic response at 3 months from the axi-cel infusion as a primary endpoint in patients with high-risk relapsed/refractory large B-cell lymphoma who are ineligible for autologous stem cell transplantation (Houot et al, Nature Medicine 2023). This study showed a significant improvement in complete metabolic response rate at 3 months based on historical controls (primary endpoint). However, there is little data on health-related quality of life (HRQoL) in this population of frail patients treated with CAR T-cells. The present study reports the HRQoL results as a secondary endpoint.

Methods: HRQoL was assessed using the EORTC QLQ-C30 cancer-specific questionnaire, the QLQ-NHL-HG29 high grade non-Hodgkin lymphoma module, and the EQ-5D-5L generic questionnaire at baseline, immediately before lymphodepletion, and at 1, 3, 6, 12, 24 and 36 months after CAR-T cell infusion. HRQoL scores were reported using mean and 95% confidence interval (95% CI) at baseline and at 3 months after infusion. Proportion of patients with deteriorated, stable and improved HRQoL at 3 months was reported for each HRQoL score. Adjusted mean change in HRQoL level using mixed model for repeated measure (MMRM) was described at each follow-up time up to 12 months and compared to baseline with a 95% CI. Clinically relevant change was defined as a change of at least 10 points for the QLQ-C30 and QLQ-NHL-HG29, 7 points for the EQ-5D-5L visual analogue scale (VAS), and 0.06 points for the EQ-5D-5L utility score. Unadjusted comparisons between ALYCANTE and ZUMA-7 phase III trial (Axi-cel arm) results were done as exploratory analysis at similar timepoints. Three dimensions (EORTC QLQ-C30 global health status, physical functioning and EQ-5D-5L VAS) were prespecified for the MMRM analyses.

Results: Among the 62 patients included in the ALYCANTE trial, 61 patients (98%) completed baseline and at least one post-baseline HRQoL evaluation. Patients presented a lower symptomatic level (lower HRQoL score) at 3 months compared to baseline with a clinically significant difference (greater than the clinical threshold of 10 points) for pain (mean = 11.9 [95% CI 5.4;18.4] at 3 months vs 25.1 [95% CI 17.7;32.6] at baseline), emotional impact (mean = 12.9 [95% CI 8.6;17.2] vs 23.8 [95% CI 17.9;29.6]) and worries/fears about health and functioning (mean = 22.1 [95% CI 16.8;27.3] vs 33.0 [95% CI 27.2;38.8]). At 1 month post-infusion, we observed a clinically and statistically significant deterioration (greater than the clinical threshold) in HRQoL for 4/22 dimensions and stable states (i.e. within the pre-defined clinical threshold) for the other 18/22 dimensions compared to baseline. Regarding the three prespecified dimensions, patients presented a significant deterioration for physical functioning (adjusted mean = -14.2 [95% CI -19.7;-8.7]) and stable states for global health status (-5.9 [95% CI -10.3;-1.5]) and VAS (0.4 [95% CI -4.0;4.7]) compared to baseline. At 3 months post-infusion, 45% of patients (N=18) and 73% of patients (N=30) presented a stable global health status and physical functioning, respectively, and 58% of patients (N=22) experienced an improvement in VAS compared to baseline. At 12 months, we observed a clinically and statistically significant improvement in HRQoL for 3/22 dimensions, including VAS (15.4 [95% CI 10.2;20.6]), and stable states in all other dimensions. In the exploratory analyses, baseline HRQoL level was similar between ALYCANTE and ZUMA-7, except for VAS (meanALYCANTE = 63.5 [95% CI 58.7;68.3] vs meanZUMA-7 = 72.4 [95% CI 69.5;75.2], with a difference exceeding the 7 points) in favor of ZUMA-7 patients and utility score (meanALYCANTE = 0.87 [95% CI 0.82;0.92] vs meanZUMA-7 = 0.80 [95% CI 0.77;0.84], with a difference exceeding the 0.06 points) in favor of ALYCANTE patients. Regarding the MMRM analysis for the three prespecified dimensions, similar results were observed over time between ALYCANTE and ZUMA-7.

Conclusions: Transplant-ineligible patients with high-risk relapsed/refractory large B-cell lymphoma treated with Axi-cel in second-line experienced an initial deterioration of HRQoL at 1 month after CAR-T cell infusion in a few dimensions, followed by either a return to the baseline score (stability) or an improvement after 3 months.

Disclosures: Bachy: ADC Therapeutics: Honoraria; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie, Roche, Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Other: Personal Fees, Research Funding; Janssen: Consultancy, Honoraria; Novartis: Honoraria, Other: Personal Fees; BeiGene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Pfizer: Honoraria, Other: Personal Fees; Kite, a Gilead Company: Consultancy, Honoraria, Other: Personal Fees. Cartron: Takeda: Honoraria; Roche, BMS, AbbVie, Ownards therapeutics, MAbQi, MedXcell, BeiGene: Consultancy; Gilead: Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Honoraria; Novartis: Honoraria; Roche: Consultancy, Honoraria; Ownards therapeutics: Consultancy; Beigene: Consultancy, Honoraria; BMS: Consultancy, Honoraria; MAbQi: Consultancy; Roche, BMS, Gilead, Novartis, Takeda, Beigen, Janssen, AbbVie: Honoraria; MedXcell: Consultancy. Morschhauser: Kite/Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Eisai: Honoraria; Epizyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genmab: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche/Genentech: Consultancy, Honoraria, Other: Payment for Expert Testimony, Honoraria for Scientific Lectures; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy. Oberic: Kite, a Gilead Company: Honoraria; Beigene: Honoraria; Roche: Honoraria; Janssen: Honoraria. Gastinne: Gilead/Kite: Honoraria; Gilead/Kite, BMS: Membership on an entity's Board of Directors or advisory committees; Roche: Other. Dulery: Takeda: Honoraria; Novartis: Honoraria; DCP-AP-HP: Research Funding; Philippe Foundation: Research Funding; Servier Foundation: Research Funding; Monahan Foundation: Research Funding; Arthur Sachs: Research Funding; Ligue Contre Le Cancer: Research Funding; Kite/Hilead: Other: Non-financial support. Thieblemont: AstraZeneca: Honoraria; ADC Therapeutics: Honoraria; Incyte Corporation: Consultancy, Honoraria, Speakers Bureau; Sanofi: Honoraria; Novartis: Consultancy, Honoraria, Other: Travel and accommodation, Speakers Bureau; Cellectis: Honoraria; Janssen: Consultancy, Honoraria, Other: Travel and accommodation, Research Funding, Speakers Bureau; Bayer: Consultancy, Honoraria, Other: Travel and accommodation, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel and accommodation, Research Funding, Speakers Bureau; BeiGene: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Other: Travel and accommodations, Research Funding, Speakers Bureau; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Other: Travel and accommodation, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Travel and Accommodation, Speakers Bureau; Kite/Gilead: Consultancy, Honoraria, Other: Travel and accommodation, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: Travel and accommodation, Speakers Bureau; University of Paris: Current Employment, Ended employment in the past 24 months; Regeneron: Consultancy, Honoraria. Jardin: Abbvie: Honoraria; Roche: Honoraria; Janssen: Honoraria; Kite, a Gilead Company: Honoraria; Novartis: Honoraria. Choquet: Kite-Gilead: Honoraria. Casasnovas: Kite-Gilead: Honoraria. Brisou: Kite-Gilead: Honoraria. Houot: Kite-Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead, Novartis, Bristol-Myers Squibb/Celgene, Incyte, Miltenyi, Roche, Abbvie: Consultancy; Kite/Gilead, Novartis, Incyte, Janssen, MSD, Takeda, Roche, Abbvie: Honoraria.

*signifies non-member of ASH