March 2022: 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.) per il trattamento di pazienti adulti con mieloma multiplo recidivato o refrattario.
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 sperimentazione clinica that looked at the safety and efficacy of ciltacabtagene autoleucel in 97 patients with relapsed or refractory mieloma multiplo 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 sindrome da rilascio di citochine (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 ha un piano di valutazione e mitigazione del rischio che richiede agli ospedali e alle cliniche che distribuiscono la terapia di essere particolarmente certificati per riconoscere e affrontare la CRS e le tossicità del sistema nervoso. La FDA chiede alla società di condurre uno studio osservazionale post-marketing che coinvolga pazienti trattati con ciltacabtagene autoleucel per valutare la sicurezza a lungo termine.
CARVYKTI viene somministrato alla dose di 0.5-1.0106 cellule T vitali CAR-positive per kg di peso corporeo, con una dose massima di 1108 cellule T vitali CAR-positive per infusione.
