Maart 2022: Na vier of meer vorige reëls van terapie, insluitend 'n proteasoom inhibeerder (PI), 'n immunomodulerende middel (IMiD) en 'n anti-CD38 monoklonale teenliggaam, het die Food and Drug Administration ciltacabtagene autoleucel goedgekeur (CARVYKTI, Janssen Biotech, Inc.) vir die behandeling van volwasse pasiënte met terugval of refraktêre veelvuldige myeloom.
Ciltacabtagene autoleucel is 'n geneties gemanipuleerde outoloë chimeriese antigeenreseptor CAR T-selterapiebehandeling wat die B-sel rypwordingsantigeen (BCMA) teiken. Elke dosis word aangepas vir die pasiënt se eie T-selle, wat geoes word, geneties gemodifiseer word en dan weer in die pasiënt ingebring word.
CARTITUDE-1 (NCT03548207) was an open label, multicenter kliniese proef that looked at the safety and efficacy of ciltacabtagene autoleucel in 97 patients with relapsed or refractory veelvuldige myeloom 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 sitokienvrystellingsindroom (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 het 'n risiko-evaluering en versagtingsplan wat vereis dat hospitale en klinieke wat die terapie versprei, spesifiek gesertifiseer moet wees om CRS- en senuweestelseltoksisiteite te herken en aan te spreek. Die FDA vra die maatskappy om 'n post-bemarking waarnemingstudie uit te voer met pasiënte wat met ciltacabtagene autoleucel behandel is om langtermynveiligheid te bepaal.
CARVYKTI word gegee teen 'n dosis van 0.5-1.0106 CAR-positiewe lewensvatbare T-selle per kg liggaamsgewig, met 'n maksimum dosis van 1108 CAR-positiewe lewensvatbare T-selle per infusie.
