2022 Maret: Setelah empat atau lebih lini terapi sebelumnya, termasuk proteasome inhibitor (PI), agen imunomodulator (IMiD), dan antibodi monoklonal anti-CD38, Food and Drug Administration telah menyetujui ciltacabtagene autoleucel (CARVYKTI, Janssen Biotech, Inc.) untuk pengobatan pasien dewasa dengan multiple myeloma yang kambuh atau refrakter.
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 uji klinis that looked at the safety and efficacy of ciltacabtagene autoleucel in 97 patients with relapsed or refractory mieloma multipel 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 pelepasan sitokin (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 memiliki evaluasi risiko dan rencana mitigasi yang mengharuskan rumah sakit dan klinik yang mendistribusikan terapi untuk disertifikasi secara khusus untuk mengenali dan mengatasi CRS dan toksisitas sistem saraf. FDA meminta perusahaan untuk melakukan studi observasi pasca-pemasaran yang melibatkan pasien yang diobati dengan autoleucel ciltacabtagene untuk menilai keamanan jangka panjang.
CARVYKTI diberikan dengan dosis 0.5-1.0106 sel T viabel CAR-positif per kg berat badan, dengan dosis maksimum 1108 sel T viabel CAR-positif per infus.
