2022 Martie: 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.) pentru tratamentul pacienților adulți cu mielom multiplu recidivat sau refractar.
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 studiu clinic that looked at the safety and efficacy of ciltacabtagene autoleucel in 97 patients with relapsed or refractory mielom multiplu 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 sindromul de eliberare de citokine (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 are un plan de evaluare și atenuare a riscurilor care necesită ca spitalele și clinicile care distribuie terapia să fie certificate în mod special pentru a recunoaște și aborda toxicitățile SRC și ale sistemului nervos. FDA cere companiei să efectueze un studiu observațional după punerea pe piață care să implice pacienți tratați cu ciltacabtagene autoleucel pentru a evalua siguranța pe termen lung.
CARVYKTI se administrează în doză de 0.5-1.0106 celule T viabile CAR pozitive per kg de greutate corporală, cu o doză maximă de 1108 celule T viabile CAR pozitive per perfuzie.
