2022 ožujak: Nakon četiri ili više prethodnih linija terapije, uključujući inhibitor proteasoma (PI), imunomodulatorno sredstvo (IMiD) i anti-CD38 monoklonsko protutijelo, Uprava za hranu i lijekove odobrila je ciltacabtagene autoleucel (CARVYKTI, Janssen Biotech, Inc.) za liječenje odraslih bolesnika s relapsom ili refraktornim multiplim mijelomom.
Ciltacabtagene autoleucel je genetski modificiran autologni himerni antigenski receptor CAR T-staničnog terapeutskog tretmana koji cilja na antigen sazrijevanja B-stanica (BCMA). Svaka je doza prilagođena pacijentovim vlastitim T-stanicama, koje se prikupljaju, genetski modificiraju i zatim ponovno unose u pacijenta.
CARTITUDE-1 (NCT03548207) was an open label, multicenter kliničko ispitivanje that looked at the safety and efficacy of ciltacabtagene autoleucel in 97 patients with relapsed or refractory multipli mijelom 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 sindrom oslobađanja citokina (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 ima procjenu rizika i plan ublažavanja koji zahtijeva da bolnice i klinike koje distribuiraju terapiju budu posebno certificirane za prepoznavanje i rješavanje toksičnosti CRS-a i živčanog sustava. FDA traži od tvrtke da provede postmarketinšku opservacijsku studiju koja uključuje pacijente liječene ciltacabtagene autoleucelom kako bi se procijenila dugoročna sigurnost.
CARVYKTI se daje u dozi od 0.5-1.0106 CAR-pozitivnih živih T-stanica po kg tjelesne težine, s maksimalnom dozom od 1108 CAR-pozitivnih živih T-stanica po infuziji.
