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ICANS is confusion, speech difficulty, and rarely seizures after CAR-T or bispecific therapy.
ICANS, the immune effector cell-associated neurotoxicity syndrome, is the confusion, speech difficulty and occasionally seizures that can follow CAR-T cell therapy or bispecific T-cell engagers. It is more common with CD28-costimulated CAR-T products and is managed with steroids, and a delayed parkinsonism has been seen rarely with BCMA-directed CAR-T such as cilta-cel. The term appears in the Acute lymphoblastic leukaemia, Diffuse large B-cell lymphoma and Multiple myeloma entries and in the drug records for Tisagenlecleucel, Obecabtagene autoleucel, Lisocabtagene maraleucel, Idecabtagene vicleucel and Epcoritamab. It also features in the bottlenecks on toxicity and the limits of the patient, on manufacturing living medicines, and on toxicity and quality of life being undervalued.
Showing the technology this term belongs to: CAR-T cell therapy.
Patients with small-cell lung cancer that has relapsed after chemotherapy now have a drug that works far better than topotecan or lurbinectedin, and it is the first T-cell engager approved for a solid tumour. Treatment requires inpatient monitoring for the first doses because of cytokine release syndrome, which most centres now manage on a short-stay basis. It does not yet apply to first-line treatment, where trials are ongoing.
CD20 x CD3 bispecifics gave patients whose lymphoma has failed CAR-T, or who cannot access it, an effective off-the-shelf treatment that can be started within days. Epcoritamab and glofitamab are now standard third-line options and are moving into earlier lines and combinations. They do not yet replace CAR-T, whose remissions appear more durable.
Axicabtagene ciloleucel as an option in relapsed follicular and marginal zone lymphoma. Compared with tisagenlecleucel in ELARA, the response rates are higher and the neurological toxicity substantially greater, which is the trade-off a patient and centre weigh.
Chemotherapy-free cellular therapy for follicular lymphoma that has stopped responding, with a toxicity profile mild enough that the treatment is deliverable outside the largest centres.
TRANSFORM confirmed ZUMA-7's conclusion with a different CD19 CAR-T and a more permissive design that allowed bridging chemotherapy, making the results closer to real-world practice. Liso-cel's low toxicity makes it attractive for older or frailer patients and for outpatient delivery. Together the two trials made CAR-T the standard second-line therapy for early-relapsing aggressive lymphoma.
ZUMA-7 rewrote second-line treatment for aggressive lymphoma: patients whose disease returns within a year of R-CHOP should be offered CAR-T rather than salvage chemotherapy and transplant. It is also one of the few cell-therapy trials to show an overall survival benefit despite crossover. Patients relapsing later than 12 months were not studied and transplant remains standard for them if chemosensitive.
Checkpoint inhibitors are now given to hundreds of thousands of patients a year, many in community clinics and emergency departments, so a common, explicit playbook for their autoimmune side effects saves lives. The guideline standardised when to stop, when to give steroids and when to escalate, and made multidisciplinary toxicity teams routine. It does not remove the judgement needed for rare events or for patients whose cancer is responding.
CARTITUDE-1 showed that a single CAR-T infusion can put late-stage myeloma into deep, multi-year remission, leading to FDA approval of cilta-cel in 2022 for heavily pretreated disease. It set the efficacy bar for BCMA-directed therapy and motivated moving CAR-T earlier (CARTITUDE-4). Late neurological toxicity and secondary malignancies remain the safety questions.
Shares Obecabtagene autoleucel, Idecabtagene vicleucel, ICANS, and whether thinking recovers after CAR-T, Step-up dosing (T-cell engagers).
Shares Treatment at the local hospital or at a cell-therapy centre far from home, Transplant or CAR-T at second line in diffuse large B-cell lymphoma, Brexucabtagene autoleucel, ELARA.
Shares Transplant or CAR-T at second line in diffuse large B-cell lymphoma, TRANSFORM: liso-cel CAR-T versus salvage chemotherapy and transplant in early-relapsing large B-cell lymphoma, Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study, JULIET.
Shares Transplant or CAR-T at second line in diffuse large B-cell lymphoma, JULIET: tisagenlecleucel for adults with relapsed or refractory diffuse large B-cell lymphoma, TRANSFORM: liso-cel CAR-T versus salvage chemotherapy and transplant in early-relapsing large B-cell lymphoma, JULIET.
Shares Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study, TRANSCEND NHL 001, ZUMA-7: axi-cel CAR-T instead of salvage chemotherapy and transplant for large B-cell lymphoma that relapses early, Lisocabtagene maraleucel.
Shares Transplant or CAR-T at second line in diffuse large B-cell lymphoma, TRANSFORM: liso-cel CAR-T versus salvage chemotherapy and transplant in early-relapsing large B-cell lymphoma, JULIET, ZUMA-1: axicabtagene ciloleucel for refractory large B-cell lymphoma, the first CAR-T approved for lymphoma.
Shares CD20 bispecific antibodies: step-up dosing, fixed duration and what it is like to take one, Cytokine release syndrome and ICANS: grading and management, Lisocabtagene maraleucel, Epcoritamab.
Shares JULIET: tisagenlecleucel for adults with relapsed or refractory diffuse large B-cell lymphoma, TRANSFORM: liso-cel CAR-T versus salvage chemotherapy and transplant in early-relapsing large B-cell lymphoma, JULIET, ZUMA-7: axi-cel CAR-T instead of salvage chemotherapy and transplant for large B-cell lymphoma that relapses early.