2022 marec: Po štirih ali več predhodnih linijah zdravljenja, vključno z zaviralcem proteasoma (PI), imunomodulatorjem (IMiD) in monoklonskim protitelesom proti CD38, je Uprava za hrano in zdravila odobrila ciltacabtagene autoleucel (CARVYKTI, Janssen Biotech, Inc.) za zdravljenje odraslih bolnikov z recidivom ali neodzivnim diseminiranim plazmocitomom.
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 klinično preskušanje that looked at the safety and efficacy of ciltacabtagene autoleucel in 97 patients with relapsed or refractory multipli mielom 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 sproščanja citokinov (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 načrt za oceno tveganja in ublažitev, ki zahteva, da so bolnišnice in klinike, ki distribuirajo terapijo, posebej certificirane za prepoznavanje in obravnavanje CRS in toksičnosti za živčni sistem. FDA prosi podjetje, da izvede postmarketinško opazovalno študijo, ki vključuje bolnike, zdravljene s ciltacabtagene autoleucelom, da oceni dolgoročno varnost.
CARVYKTI se daje v odmerku 0.5-1.0106 CAR-pozitivnih živih T-celic na kg telesne mase, z največjim odmerkom 1108 CAR-pozitivnih živih T-celic na infuzijo.
