{"entity":{"id":"lisocabtagene-maraleucel","kind":"drug","name":"Lisocabtagene maraleucel","aka":[],"tldr":"Lisocabtagene maraleucel is the only CAR-T approved for chronic lymphocytic leukaemia, for patients whose disease has outrun both BTK and BCL-2 inhibitors.","summary":"TRANSCEND CLL 004: in CLL/SLL after BTK and venetoclax failure, CR/CRi 18-20%, ORR 47%, uMRD in blood 64%, durable in complete responders; accelerated approval March 2024. Also approved in LBCL (second line, TRANSFORM), follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma (2025). Defined 1:1 CD4:CD8 composition; 4-1BB costimulation. Lower CRS/ICANS than CD28-based products.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Lisocabtagene_maraleucel","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Lisocabtagene%20maraleucel"}],"tags":[],"related":[],"cancers":["cll","dlbcl","cll-relapsed","primary-mediastinal-b-cell-lymphoma"],"sections":[],"technologies":["car-t"],"targets":["cd19"],"drugs":[],"companies":["bms"],"institutions":[],"pathways":[],"terms":["crs","icans"],"trials":["transcend-cll-004","nct07015242"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Breyanzi","code":"liso-cel","modality":"CAR-T (CD19, defined CD4:CD8)","mechanism":"Autologous CD19 CAR-T (4-1BB) manufactured as separate CD4 and CD8 components and infused at a fixed ratio.","approvals":[{"region":"US","year":2021,"indication":"Relapsed/refractory LBCL after ≥2 lines"},{"region":"US","year":2022,"indication":"Second-line LBCL (TRANSFORM)"},{"region":"US","year":2024,"indication":"Relapsed/refractory CLL/SLL after BTK inhibitor and BCL-2 inhibitor (accelerated)"}],"mechanismSteps":["Leukapheresis; CD4 and CD8 T cells transduced and expanded separately","Lymphodepletion with fludarabine/cyclophosphamide","Fixed 1:1 CD4:CD8 infusion engages CD19 on CLL cells","Expansion is slower than CD28 CARs, moderating CRS; complete responders show long-term uMRD"],"dosing":{"route":"Single IV infusion (two components)","schedule":"90-110 × 10^6 CAR+ T cells (CLL)","monitoring":"CRS/ICANS (boxed warning), prolonged cytopenias, hypogammaglobulinaemia, secondary T-cell malignancy warning","source":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Breyanzi"},"toxicity":[{"event":"Cytokine release syndrome","anyGradePct":83,"grade3PlusPct":9,"source":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Breyanzi","note":"TRANSCEND CLL 004"},{"event":"Neurotoxicity","anyGradePct":46,"grade3PlusPct":20},{"event":"Prolonged cytopenias","grade3PlusPct":54}],"access":[],"regulatoryEvents":[{"date":"2024-03-14","type":"approval","region":"US","note":"First CAR-T in CLL (TRANSCEND CLL 004), accelerated"},{"date":"2024-03-21","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint; the confirmatory requirement was still open 2.5 years later, when the FDA's table was read.","indication":"Adult patients with relapsed/ refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in patients who have received at least two prior lines of therapy including a Bruton’s tyrosine kinase (BTK) inhibitor and a B-cell lymphoma-2 (BCL-2) inhibitor"},{"date":"2024-05-15","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint, with a confirmatory trial required.","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lisocabtagene-maraleucel-follicular-lymphoma","indication":"Adult patients with relapsed or refractory follicular lymphoma (FL) who have received two or more prior lines of systemic therapy"},{"date":"2026-02-20","type":"conversion","region":"US","note":"Confirmed: the accelerated approval of 2024 converted to traditional approval 1.8 years after it was granted.","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lisocabtagene-maraleucel-follicular-lymphoma","indication":"Adult patients with relapsed or refractory follicular lymphoma (FL) who have received two or more prior lines of systemic therapy"}]},"route":"/drugs/lisocabtagene-maraleucel/","neighbours":{"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"follicular-lymphoma","kind":"cancer","name":"Follicular lymphoma","route":"/cancers/follicular-lymphoma/"},{"id":"mantle-cell-lymphoma","kind":"cancer","name":"Mantle cell lymphoma","route":"/cancers/mantle-cell-lymphoma/"},{"id":"marginal-zone-lymphoma","kind":"cancer","name":"Marginal zone lymphoma","route":"/cancers/marginal-zone-lymphoma/"},{"id":"primary-mediastinal-b-cell-lymphoma","kind":"cancer","name":"Primary mediastinal (thymic) large B-cell lymphoma","route":"/cancers/primary-mediastinal-b-cell-lymphoma/"},{"id":"cll-relapsed","kind":"cancer","name":"Relapsed or refractory chronic lymphocytic leukaemia","route":"/cancers/cll-relapsed/"}],"technology":[{"id":"car-t-manufacturing-process","kind":"technology","name":"Autologous CAR-T manufacturing, batch by batch","route":"/technologies/car-t-manufacturing-process/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"}],"target":[{"id":"cd19","kind":"target","name":"CD19","route":"/targets/cd19/"},{"id":"cd28","kind":"target","name":"CD28","route":"/targets/cd28/"}],"company":[{"id":"bms","kind":"company","name":"Bristol Myers Squibb","route":"/companies/bms/"}],"term":[{"id":"btki-bcl2i-resistance-mutations","kind":"term","name":"BTK C481S, PLCG2 and BCL2 G101V resistance mutations","route":"/terms/btki-bcl2i-resistance-mutations/"},{"id":"crs","kind":"term","name":"Cytokine release syndrome (CRS)","route":"/terms/crs/"},{"id":"lymphoma-tx-crs-icans","kind":"term","name":"Cytokine release syndrome and ICANS: grading and management","route":"/terms/lymphoma-tx-crs-icans/"},{"id":"icans","kind":"term","name":"ICANS (neurotoxicity)","route":"/terms/icans/"},{"id":"lymphoma-tx-immunoglobulin-replacement","kind":"term","name":"Immunoglobulin replacement after CAR-T, bispecifics and long anti-CD20 treatment","route":"/terms/lymphoma-tx-immunoglobulin-replacement/"},{"id":"lymphoma-tx-car-t-pathway","kind":"term","name":"The CAR-T pathway in lymphoma: referral, apheresis, bridging and the waiting","route":"/terms/lymphoma-tx-car-t-pathway/"},{"id":"lymphoma-tx-uk-access","kind":"term","name":"What the NHS in England funds for lymphoma, appraisal by appraisal","route":"/terms/lymphoma-tx-uk-access/"}],"trial":[{"id":"nct07015242","kind":"trial","name":"A Study of the Efficacy and Safety of Lisocabtagene Maraleucel (Liso-cel) as First-Line Therapy in Adults With Transplant-Ineligible Primary Central Nervous System Lymphoma","route":"/trials/nct07015242/"},{"id":"transcend-cll-004","kind":"trial","name":"TRANSCEND CLL 004","route":"/trials/transcend-cll-004/"},{"id":"transcend-nhl-001","kind":"trial","name":"TRANSCEND NHL 001","route":"/trials/transcend-nhl-001/"}],"paper":[{"id":"paper-transcend-nhl-001-liso-cel-lancet-2020","kind":"paper","name":"Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study","route":"/key-papers/paper-transcend-nhl-001-liso-cel-lancet-2020/"},{"id":"paper-transform-liso-cel-lancet-2022","kind":"paper","name":"TRANSFORM: liso-cel CAR-T versus salvage chemotherapy and transplant in early-relapsing large B-cell lymphoma","route":"/key-papers/paper-transform-liso-cel-lancet-2022/"}],"roadmap":[{"id":"lymphoma-roadmap","kind":"roadmap","name":"Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting","route":"/roadmaps/lymphoma-roadmap/"}],"idea":[{"id":"lymphoma-ev-manufacturing-time-as-a-trial-endpoint","kind":"idea","name":"Report the time from apheresis to infusion as a trial endpoint, not a logistics footnote","route":"/ideas/lymphoma-ev-manufacturing-time-as-a-trial-endpoint/"}],"person":[{"id":"stanley-riddell","kind":"person","name":"Stanley R. Riddell","route":"/people/stanley-riddell/"}],"biomarker":[{"id":"cd19-expression","kind":"biomarker","name":"CD19 expression (CD19-positive)","route":"/biomarkers/cd19-expression/"}]}}