Real-world comparison of lisocabtagene maraleucel and axicabtagene ciloleucel in large B-cell lymphoma: an inverse probability of treatment weighting analysis with 3-year follow up
Lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel) are FDA- and EMAapproved chimeric antigen receptor (CAR) T-cell therapies for relapsed/refractory large B-cell lymphoma (LBCL). However, comparative real-world analyses of their efficacy and toxicity with extended follow-up ar...
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| Vydáno v: | Haematologica (Roma) Ročník 110; číslo 9; s. 2040 - 2054 |
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Fondazione Ferrata Storti
01.09.2025
Ferrata Storti Foundation |
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| Abstract | Lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel) are FDA- and EMAapproved chimeric antigen receptor (CAR) T-cell therapies for relapsed/refractory large B-cell lymphoma (LBCL). However, comparative real-world analyses of their efficacy and toxicity with extended follow-up are lacking. We conducted a retrospective study of 160 LBCL patients treated at the Fred Hutchinson Cancer Center with commercial liso-cel or axi-cel per standard of care. Using inverse probability of treatment weighting (IPTW) to mitigate treatment allocation bias and multivariable adjustments to minimize other sources of confounding, we assessed the impact of CAR T-cell product type on outcomes. Axi-cel was associated with significantly higher rates of cytokine release syndrome (CRS; G1+: adjusted OR [aOR] 4.27, p=0.004; G2+: aOR 2.88, p=0.006), immune effector cell-associated neurotoxicity syndrome (ICANS; G1+: aOR 2.10, p=0.048), and immune effector cell-associated hematotoxicity (ICAHT; G1+: aOR 8.09, p |
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| AbstractList | Lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel) are FDA- and EMAapproved chimeric antigen receptor (CAR) T-cell therapies for relapsed/refractory large B-cell lymphoma (LBCL). However, comparative real-world analyses of their efficacy and toxicity with extended follow-up are lacking. We conducted a retrospective study of 160 LBCL patients treated at the Fred Hutchinson Cancer Center with commercial liso-cel or axi-cel per standard of care. Using inverse probability of treatment weighting (IPTW) to mitigate treatment allocation bias and multivariable adjustments to minimize other sources of confounding, we assessed the impact of CAR T-cell product type on outcomes. Axi-cel was associated with significantly higher rates of cytokine release syndrome (CRS; G1+: adjusted OR [aOR] 4.27, p=0.004; G2+: aOR 2.88, p=0.006), immune effector cell-associated neurotoxicity syndrome (ICANS; G1+: aOR 2.10, p=0.048), and immune effector cell-associated hematotoxicity (ICAHT; G1+: aOR 8.09, p Lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel) are Food and Drug Administration- and European Medicines Agency-approved chimeric antigen receptor (CAR) T-cell therapies for relapsed/refractory large B-cell lymphoma (LBCL). However, comparative real-world analyses of their efficacy and toxicity with extended follow-up are lacking. We conducted a retrospective study of 160 LBCL patients treated at the Fred Hutchinson Cancer Center with commercial liso-cel or axi-cel per standard of care. Using inverse probability of treatment weighting (IPTW) to mitigate treatment allocation bias and multivariable adjustments to minimize other sources of confounding, we assessed the impact of CAR T-cell product type on outcomes. Axi-cel was associated with significantly higher rates of cytokine release syndrome (CRS; grade [G]1+: adjusted odds ratio [aOR] =4.27; P=0.004; G2+: aOR=2.88; P=0.006), immune effector cell-associated neurotoxicity syndrome (ICANS; G1+: aOR=2.10; P=0.048), and immune effector cell-associated hematotoxicity (ICAHT; G1+: aOR=8.09; P<0.001; G2+: aOR=3.86; P=0.001). Axi-cel was also associated with more frequent use of supportive care measures, such as tocilizumab (aOR=2.50; P=0.017), dexamethasone (aOR=2.77; P=0.007), and cefepime (aOR=3.37; P=0.001). We could not confirm statistically significant differences in the response rates and survival outcomes after liso-cel versus axi-cel (complete response: aOR=1.12; P=0.8; overall survival: adjusted hazard ratio [aHR] =1.34; P=0.3; progression-free survival: aHR=0.97; P=0.9; duration of response: aHR=0.89; P=0.7; cumulative incidence of relapse: aHR=0.92; P=0.8). In summary, although axicel was associated with greater toxicity requiring more intensive management, the response rates and survival outcomes were comparable between axi-cel and liso-cel. Lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel) are Food and Drug Administration- and European Medicines Agency-approved chimeric antigen receptor (CAR) T-cell therapies for relapsed/refractory large B-cell lymphoma (LBCL). However, comparative real-world analyses of their efficacy and toxicity with extended follow-up are lacking. We conducted a retrospective study of 160 LBCL patients treated at the Fred Hutchinson Cancer Center with commercial liso- cel or axi-cel per standard of care. Using inverse probability of treatment weighting (IPTW) to mitigate treatment allocation bias and multivariable adjustments to minimize other sources of confounding, we assessed the impact of CAR T-cell product type on outcomes. Axi-cel was associated with significantly higher rates of cytokine release syndrome (CRS; grade [G]1+: adjusted odds ratio [aOR] =4.27; P=0.004; G2+: aOR=2.88; P=0.006), immune effector cell-associated neurotoxicity syndrome (ICANS; G1+: aOR=2.10; P=0.048), and immune effector cell-associated hematotoxicity (ICAHT; G1+: aOR=8.09; P<0.001; G2+: aOR=3.86; P=0.001). Axi-cel was also associated with more frequent use of supportive care measures, such as tocilizumab (aOR=2.50; P=0.017), dexamethasone (aOR=2.77; P=0.007), and cefepime (aOR=3.37; P=0.001). We could not confirm statistically significant differences in the response rates and survival outcomes after liso-cel versus axi-cel (complete response: aOR=1.12; P=0.8; overall survival: adjusted hazard ratio [aHR] =1.34; P=0.3; progression-free survival: aHR=0.97; P=0.9; duration of response: aHR=0.89; P=0.7; cumulative incidence of relapse: aHR=0.92; P=0.8). In summary, although axicel was associated with greater toxicity requiring more intensive management, the response rates and survival outcomes were comparable between axi-cel and liso-cel.Lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel) are Food and Drug Administration- and European Medicines Agency-approved chimeric antigen receptor (CAR) T-cell therapies for relapsed/refractory large B-cell lymphoma (LBCL). However, comparative real-world analyses of their efficacy and toxicity with extended follow-up are lacking. We conducted a retrospective study of 160 LBCL patients treated at the Fred Hutchinson Cancer Center with commercial liso- cel or axi-cel per standard of care. Using inverse probability of treatment weighting (IPTW) to mitigate treatment allocation bias and multivariable adjustments to minimize other sources of confounding, we assessed the impact of CAR T-cell product type on outcomes. Axi-cel was associated with significantly higher rates of cytokine release syndrome (CRS; grade [G]1+: adjusted odds ratio [aOR] =4.27; P=0.004; G2+: aOR=2.88; P=0.006), immune effector cell-associated neurotoxicity syndrome (ICANS; G1+: aOR=2.10; P=0.048), and immune effector cell-associated hematotoxicity (ICAHT; G1+: aOR=8.09; P<0.001; G2+: aOR=3.86; P=0.001). Axi-cel was also associated with more frequent use of supportive care measures, such as tocilizumab (aOR=2.50; P=0.017), dexamethasone (aOR=2.77; P=0.007), and cefepime (aOR=3.37; P=0.001). We could not confirm statistically significant differences in the response rates and survival outcomes after liso-cel versus axi-cel (complete response: aOR=1.12; P=0.8; overall survival: adjusted hazard ratio [aHR] =1.34; P=0.3; progression-free survival: aHR=0.97; P=0.9; duration of response: aHR=0.89; P=0.7; cumulative incidence of relapse: aHR=0.92; P=0.8). In summary, although axicel was associated with greater toxicity requiring more intensive management, the response rates and survival outcomes were comparable between axi-cel and liso-cel. |
| Author | Till, Brian G. Iovino, Lorenzo Wu, Qian Vicky Kimble, Erik L. Gopal, Ajay K. Hirayama, Alexandre V. Shadman, Mazyar Cassaday, Ryan D. Poh, Christina Otegbeye, Folashade Maloney, David G. Gauthier, Jordan Chapuis, Aude G. Jeon, Yein Portuguese, Andrew J. Huang, Jennifer J. Taheri, Mahnoosh Liang, Emily C. Basom, Ryan S. Albittar, Aya Milano, Filippo |
| AuthorAffiliation | 2 University of Washington , Seattle, WA 1 Fred Hutchinson Cancer Center , Seattle, WA 3 Washington State University, Pullman, WA 4 MD Anderson Cancer Center, Houston, TX, USA |
| AuthorAffiliation_xml | – name: 1 Fred Hutchinson Cancer Center , Seattle, WA – name: 2 University of Washington , Seattle, WA – name: 4 MD Anderson Cancer Center, Houston, TX, USA – name: 3 Washington State University, Pullman, WA |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 AJP reports consultancy/honoraria from Capvision and Karyopharm Therapeutics. AVH has received research funding from Juno Therapeutics and Nektar Therapeutics; and has received honoraria from Bristol Myers Squibb. AKG has received research funding from Merck, BMS, Gilead Sciences, Seagen, Teva, Pfizer, Janssen Oncology, Millennium, IgM, I-Mab, Takeda, BeiGene, and AstraZeneca; and reports consultancy/honoraria from Pfizer, Seagen, Janssen Oncology, SciTek, Compliment Corporation, Millennium, Gilead Sciences, Nurix, Cellectar, Kite/Gilead, Morphosys/Incyte, I-Mab, TG Therapeutics, Pfizer, ADC therapeutics, Amgen, Actinium Pharmaceuticals, Takeda, Epizyme, and Merck. RDC has received research funding from Amgen, Kite/Gilead, Incyte, Merck, Pfizer, Servier, and Vanda Pharmaceuticals; consultancy/honoraria from Amgen, Autolus, Jazz, Kite/Gilead, and Pfizer; discloses membership on a board or advisory committee for Autolus and PeproMene Bio; and discloses that spouse was employed by and owned stock in Seagen. BGT reports research funding from Mustang Bio and Juno Therapeutics; patents/ royalties from Mustang Bio; and consultancy for Mustang Bio and Proteios Technology. DGM has received research funding from Kite, Juno Therapeutics, Celgene, Legend Biotech, and BMS; honoraria from BMS, Caribou Biosciences, Inc. Celgene, Genentech, Incyte, Juno Therapeutics, Kite, Lily, Mustang Bio, Novartis, and Umoja; and reports membership on a board or advisory committee for A2 Biotherapeutics, Navan Technologies, Chimeric Therapeutics, Genentech, BMS, ImmPACT Bio, Gilead Sciences, Interius, and BMS. Disclosures |
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| Snippet | Lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel) are FDA- and EMAapproved chimeric antigen receptor (CAR) T-cell therapies for... Lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel) are Food and Drug Administration- and European Medicines Agency-approved chimeric... |
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| SubjectTerms | Adult Aged Aged, 80 and over Antigens, CD19 - therapeutic use Biological Products Cell Therapy & Immunotherapy Female Follow-Up Studies Humans Immunotherapy, Adoptive - adverse effects Immunotherapy, Adoptive - methods Lymphoma, Large B-Cell, Diffuse - drug therapy Lymphoma, Large B-Cell, Diffuse - immunology Lymphoma, Large B-Cell, Diffuse - mortality Lymphoma, Large B-Cell, Diffuse - pathology Lymphoma, Large B-Cell, Diffuse - therapy Male Middle Aged Receptors, Chimeric Antigen Retrospective Studies Tissue Extracts - adverse effects Tissue Extracts - therapeutic use Treatment Outcome |
| Title | Real-world comparison of lisocabtagene maraleucel and axicabtagene ciloleucel in large B-cell lymphoma: an inverse probability of treatment weighting analysis with 3-year follow up |
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