2022 mars: After four or more prior lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody, the Food and Drug Administration has approved ciltacabtagene autoleucel (CARVYKTI, Janssen Biotech, Inc.) pour le traitement des patients adultes atteints de myélome multiple récidivant ou réfractaire.
Ciltacabtagene autoleucel is a genetically engineered autologous chimeric antigen receptor CAR T-cell therapy treatment that targets the B-cell maturation antigen (BCMA). Each dose is tailored to the patient’s own T-cells, which are harvested, genetically modified, and then reintroduced into the patient.
CARTITUDE-1 (NCT03548207) was an open label, multicenter essai clinique that looked at the safety and efficacy of ciltacabtagene autoleucel in 97 patients with relapsed or refractory le myélome multiple who had received at least three prior lines of therapy, including a PI, an IMiD, and an anti-CD38 monoclonal antibody, and who had disease progression on or after the last chemotherapy regimen Patients were given 0.51.0106 CAR-positive viable T cells per kg body weight of ciltacabtagene autoleucel. Efficacy was determined by an Independent Review committee utilising the International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma to assess overall response rate (ORR) and duration of response (DOR). The ORR was 97.9% (95 percent confidence interval: 92.7 percent, 99.7%). The median duration of response (DOR) was 21.8 months (95 percent CI: 21.8, NE) among the 95 patients who responded, with a median follow-up period of 18 months.
The CARVYKTI label includes a boxed warning for syndrome de libération de cytokines (CRS), hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), Parkinsonism and Guillain-Barré syndrome and their complications, and prolonged and/or recurrent cytopenia, which can all be fatal or life-threatening. Pyrexia, cytokine release syndrome, hypogammaglobulinemia, musculoskeletal pain, fatigue, infections, diarrhoea, nausea, encephalopathy, headache, coagulopathy, constipation, and vomiting were the most prevalent side effects of ciltacabtagene autoleucel.
CARVYKTI a un plan d'évaluation et d'atténuation des risques qui exige que les hôpitaux et les cliniques qui distribuent la thérapie soient particulièrement certifiés pour reconnaître et traiter les toxicités du SRC et du système nerveux. La FDA demande à la société de mener une étude observationnelle post-commercialisation impliquant des patients traités avec l'autoleucel de ciltacabtagène afin d'évaluer l'innocuité à long terme.
CARVYKTI est administré à une dose de 0.5 à 1.0106 lymphocytes T viables CAR-positifs par kg de poids corporel, avec une dose maximale de 1108 lymphocytes T viables CAR-positifs par perfusion.
