Introduction

Lisocabtagene maraleucel (liso-cel) is an autologous CD19-directed CAR T cell therapy approved for the treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) based on the TRANSCEND (Abramson et al, Lancet 2020), TRANSFORM (Kamdar et al, Lancet 2022), and PILOT studies (Sehgal et al, Lancet Oncol 2022). Extending clinical trial results for liso-cel to the real-world setting, we performed a multicenter retrospective study to evaluate the safety and efficacy of liso-cel in standard of care practice.

Methods

Patients (pts) aged ≥18 years with LBCL who received commercial liso-cel infusion between February 2021 (time of FDA approval) and June 2023 at 7 academic US medical centers were identified from the Cell Therapy Consortium registry. Pt and treatment characteristics were summarized descriptively, and the Kaplan Meier method was used for survival outcomes. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT consensus criteria. Tumor response was assessed per Lugano criteria locally by the treating clinician.

Results

As of 6/10/2023, 101 pts underwent liso-cel infusion. Detailed baseline pt characteristics are shown in Table 1. Median age at apheresis was 71 years (range: 30-85) with 35% of pts ≥75 years, 60% were male, 16% had an ECOG PS of ≥2 at apheresis, and 11% had active secondary CNS involvement. By histology, 86% of pts had DLBCL, 7% HGBL, 5% TFL, and 2% PMBCL. Baseline comorbidities included diabetes (18%), stage IV chronic kidney disease (5%), cerebrovascular disease (5%), impaired cardiac ejection fraction (2%), pulmonary dysfunction (2%), impaired hepatic function (2%), and active infection (3%), with 68% having a Charlson Comorbidity Index score of ≥3. Due to comorbidities, 30% of pts would have been ineligible for the TRANSCEND clinical trial. The median number of prior therapies was 3 (range: 1-8) and 16% of pts underwent prior autologous stem cell transplant. Bridging therapy was used in 62% of pts including 41% receiving polatuzumab-based treatment, 24% chemoimmunotherapy, and 21% radiation therapy. Seven (7%) pts received liso-cel on an expanded access trial (NCT04400591) due to a non-conforming product. Median time from apheresis to CAR T-cell infusion was 39 days (IQR: 34-43) and 85% of CAR T-cell infusions occurred inpatient.

Any Grade CRS occurred in 49% (3% were Grade ≥3) and any Grade ICANS occurred in 26% (10% were Grade ≥3). Median onset of CRS and ICANS was 4 and 6 days following liso-cel infusion, respectively. Tocilizumab was administered in 31% and 31% of pts received steroids for toxicity management. Nine deaths (9%) unrelated to lymphoma progression occurred at a median of 1.2 months (range: 0.3-4.3) with 2 due to infectious complications, 2 due to other malignancy, 1 due to grade 5 neurologic toxicity, 1 due to concurrent grade 5 neurologic toxicity and grade 5 CRS, 1 due to accidental death, and 2 due to unknown causes. The 6-month incidence of non-relapse mortality was 8% (95% CI, 3.4% - 15%).

The overall response rate (ORR) to bridging therapy, as assessed prior to lymphodepletion, was 45% with 17% achieving a complete response (CR). Following liso-cel infusion, response assessment was performed at day 30 and/or day 90 according to treating center practice, or in those determined to have clinical progression. Of the 89 pts evaluable at day 30, the ORR was 81% with 63% achieving a CR. Among 76 pts evaluable at day 90, the ORR was 63% with 58% achieving a CR. With a median follow-up of 10.3 months (range 0.3-22.8), month 6 outcomes were 62.7% (95% CI, 52.8% - 74.3%) for progression-free survival, 71.6% (95% CI, 60.9% - 84.1%) for duration of response, and 77.1% (95% CI, 68.4% - 86.9%) for overall survival ( Figure 1).

Conclusions

These analyses confirm that efficacy and safety are similar or superior to those of patients enrolled in liso-cel prospective clinical trials for R/R LBCL. Notably, these outcomes were achieved in pts predominately of advanced age and with a significant comorbid burden, recognizing that one-third would have been ineligible for TRANSCEND. These results also likely reflect advancements in patient selection and toxicity management including the real world utilization of novel bridging therapy to temporize and debulk disease. Follow-up is ongoing and updated data will be presented at the meeting.

Riedell:CRISPR Therapeutics: Research Funding; Calibr: Research Funding; CVS Caremark: Consultancy; Sana Biotechnology: Consultancy; Nektar Therapeutics: Membership on an entity's Board of Directors or advisory committees; Intellia Therapeutics: Membership on an entity's Board of Directors or advisory committees; Nurix Therapeutics: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Genmab: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Fate Therapeutics: Research Funding; Nkarta: Research Funding; MorphoSys: Research Funding; Tessa Therapeutics: Research Funding; Roche: Research Funding; Xencor: Research Funding. Nastoupil:Gilead Sciences/Kite Pharma: Honoraria, Research Funding; Genentech, Inc., Genmab, Gilead/Kite, Janssen, Merck, Novartis, Takeda: Honoraria, Research Funding; AstraZeneca: Honoraria; Regeneron: Honoraria; AbbVie: Honoraria; Daiichi Sankyo: Honoraria, Research Funding; DeNovo: Honoraria; Caribou Biosciences: Honoraria, Research Funding; Bristol Myers Squibb/Celgene: Honoraria, Research Funding; ADC Therapeutics: Honoraria. Ahmed:Kite: Consultancy, Research Funding; BMS: Consultancy. Maziarz:AlloVir: Consultancy, Research Funding; Athersys: Other: Patent holder; Orca Therapeutics: Research Funding; Gamida: Research Funding; Kite: Consultancy; Novartis: Consultancy, Research Funding. Hu:AbbVie: Membership on an entity's Board of Directors or advisory committees. Schuster:Juno Therapeutics: Research Funding; DTRM: Research Funding; Merck: Research Funding; Nanovecter: Consultancy; Pharmacyclics: Consultancy; Celgene: Consultancy, Research Funding; BiGene: Consultancy; Acerta: Consultancy; Loxo: Consultancy; Legend Biotech: Consultancy; Janssen: Consultancy; Genentech/Roche: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; MustangBio: Consultancy; Morphosys: Consultancy; Abbvie: Research Funding; Adaptive Biotechnologies: Research Funding; TG Therapeutics: Research Funding; Nordic: Consultancy; Regeneron: Consultancy; Novartis: Consultancy, Research Funding. Chen:Fate: Research Funding; Intellia: Consultancy; Kite: Consultancy, Research Funding; Elsevier: Consultancy; Novartis: Research Funding. Oluwole:Allogene: Research Funding; Epizyme: Consultancy; Nektar: Consultancy; Cargo: Consultancy; Novartis: Consultancy; Kite, a Gilead Company/ Gilead: Consultancy, Research Funding; Caribou: Consultancy; AbbVie: Consultancy; Daiichi Sankyo: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; TGR: Consultancy; ADC: Consultancy, Speakers Bureau; Gilead: Consultancy, Honoraria. Bachanova:ADC: Membership on an entity's Board of Directors or advisory committees; Allogene: Membership on an entity's Board of Directors or advisory committees; Miltenyi: Other: DSMB; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Citius: Research Funding; Incyte: Research Funding; Gamida Cell: Research Funding. McGuirk:Juno Therapeutics: Consultancy; Kite: Consultancy, Research Funding; Allovir: Consultancy, Research Funding; EcoR1 Capital: Consultancy; Magenta Therapeutics: Consultancy; Novartis: Research Funding; Fresenius Biotech: Research Funding; Astellas Pharma: Research Funding; Bellicum Pharmaceuticals: Research Funding; Pluristem Therapeutics: Research Funding; Gamida Cell: Research Funding. Perales:Merck: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Orcabio: Consultancy, Current equity holder in publicly-traded company, Honoraria; Omeros: Consultancy, Current equity holder in publicly-traded company, Honoraria; Allovir: Consultancy; Cidara Therapeutics: Consultancy, Other; Nektar Therapeutics: Consultancy, Honoraria, Research Funding; Allogene: Research Funding; Karyopharm: Consultancy, Honoraria; Medigene: Consultancy, Other; Sellas Life Sciences: Consultancy; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; Adicet: Honoraria; Astellas: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Syncopation: Honoraria; DSMB: Other; Exevir: Consultancy, Honoraria; Equillium: Consultancy, Honoraria; Caribou: Consultancy, Honoraria; Miltenyi Biotec: Honoraria; NexImmune: Consultancy, Current equity holder in publicly-traded company; Servier: Other; Incyte: Consultancy, Honoraria, Research Funding; Kite: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; VectivBio AG: Consultancy, Honoraria; Vor Biopharma: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Celgene: Honoraria. Bishop:BMS, Kite/Gilead, Servier, AstraZeneca, ADC Therapeutics, Incyte: Speakers Bureau; Chimeric Therapeutics: Consultancy; Incyte: Honoraria, Other: Travel support, Speakers Bureau; Autolus: Consultancy, Research Funding; Triumvira: Research Funding; Immatics: Research Funding; Arcellx: Consultancy, Research Funding; WindMIL Therapeutics: Consultancy; Bluebird Bio: Consultancy; Iovance: Consultancy; Sanofi: Honoraria, Speakers Bureau; Tmunity: Research Funding; Celgene: Honoraria; Sana Biotechnology: Consultancy; CRISPR Therapeutics: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau; Servier: Speakers Bureau; ADC Therapeutics: Speakers Bureau; KITE/Gilead, Novartis, CRISPR Therapeutics, Autolus Therapeutics, BMS/JUNO Therapeutics, Incyte, Sana Biotechnology, Iovance Biotherapeutics, In8bio, Chimeric Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Honoraria, Other: Travel support, Speakers Bureau; BMS: Honoraria, Other: Travel support, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: Travel support, Research Funding. Porter:Mirror Biologics: Membership on an entity's Board of Directors or advisory committees; National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Sana Therapeutics: Consultancy, Current equity holder in publicly-traded company; Tmunity: Patents & Royalties; Genentech: Current equity holder in publicly-traded company; DeCart: Membership on an entity's Board of Directors or advisory committees; Capstan Bio: Honoraria; BMS: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Angiocrine Bio: Membership on an entity's Board of Directors or advisory committees; Wiley and Sons Publishing: Honoraria.

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2023
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