2022 март: След четири или повече предходни линии на терапия, включително протеазомен инхибитор (PI), имуномодулиращ агент (IMiD) и анти-CD38 моноклонално антитяло, Администрацията по храните и лекарствата одобри ciltacabtagene autoleucel (CARVYKTI, Janssen Biotech, Inc.) за лечение на възрастни пациенти с рецидивирал или рефрактерен мултиплен миелом.
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 клинично изпитване that looked at the safety and efficacy of ciltacabtagene autoleucel in 97 patients with relapsed or refractory множествен миелом 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 синдром на освобождаване на цитокини (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 има план за оценка и смекчаване на риска, който изисква болниците и клиниките, които разпространяват терапията, да бъдат специално сертифицирани за разпознаване и справяне с CRS и токсичността на нервната система. FDA иска от компанията да проведе постмаркетингово обсервационно проучване, включващо пациенти, лекувани с ciltacabtagene autoleucel, за да оцени дългосрочната безопасност.
CARVYKTI се прилага в доза от 0.5-1.0106 CAR-позитивни жизнеспособни Т-клетки на kg телесно тегло, с максимална доза от 1108 CAR-позитивни жизнеспособни Т-клетки на инфузия.
