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Risicomanagement en toxiciteiten van CAR-T, bispecifieke antilichamen en ADC's bij multiple myeloom

Deze narratieve review beschrijft het toxiciteitsprofiel en risicomanagement van BCMA- en GPRC5D-gedirected immunotherapieën, waaronder CAR-T-cellen, bispecifieke antilichamen en antibody-drug conjugates, bij patiënten met multiple myeloom.

De auteurs categoriseren bijwerkingen in acute (CRS, ICANS, infecties), subacute (neurologische en cardiovasculaire complicaties) en langetermijneffecten (cytopenieën, secundaire maligniteiten). Daarnaast worden gevalideerde risicotools besproken, zoals de CAR-HEMATOTOX-score en de EASIX-index, die helpen bij het voorspellen van ernstige complicaties.

Voor veilige toepassing buiten gespecialiseerde centra is een multidisciplinaire infrastructuur met duidelijke verwijspaden en gerichte monitoring essentieel, mede gezien de toenemende beschikbaarheid van off-the-shelf therapieën in de community.

Abstract (original)

B-cell maturation antigen (BCMA), G protein-coupled receptor class C group 5 member D (GPRC5D)-directed immunotherapies, chimeric antigen receptor T-cell (CAR-T) products, bispecific T-cell engagers (BsAbs), and antibody-drug conjugates (ADCs), have transformed the management of MM. Their adoption is now extending beyond tertiary centers following FDA modifications for CAR-T safety and the rapid uptake of off-the-shelf bispecifics suitable for community delivery. Clinicians outside specialist hubs must therefore be conversant with the full toxicity spectrum, including rare but high-consequence events, both for informed consent and for the work-up of post-therapy complications. In this narrative review, we report on the published literature around toxicities of approved and investigational BCMA- and GPRC5D-directed therapies, drawing on pivotal trial data, real-world cohorts, pharmacovigilance studies, and consensus management recommendations, with emphasis on practical recognition and risk mitigation. This review presents toxicities by a temporal pattern including acute (CRS, ICANS, infection, ocular, mucocutaneous), subacute (cranial nerve palsies, parkinsonism, myelitis, peripheral neuropathies IEC-associated enterocolitis and cardiovascular events), and long-term (prolonged cytopenias, second primary malignancies). We discuss validated risk stratification tools, such as the CAR-HEMATOTOX score, EASIX index, and multidisciplinary geriatric assessment, which predicts severe ICANS, infection, and resource utilization, supporting individualized pre-treatment planning. Safe delivery of immune therapies in community settings requires infrastructure for acute critical care, neurology, ophthalmology, infectious disease and long-term surveillance, but is achievable when paired with validated risk stratification and clear referral pathways.

Dit artikel is een samenvatting van een publicatie in Cancers. Voor het volledige artikel, alle details en referenties verwijzen wij u naar de oorspronkelijke bron.

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DOI: 10.3390/cancers18132083