Marts 2022: 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.) pieaugušo pacientu ar recidivējošu vai refraktāru multiplo mielomu ārstēšanai.
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 klīniskā pētījuma that looked at the safety and efficacy of ciltacabtagene autoleucel in 97 patients with relapsed or refractory multiplā mieloma 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 citokīnu atbrīvošanās sindroms (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 ir riska novērtēšanas un mazināšanas plāns, kas paredz, ka slimnīcām un klīnikām, kas izplata terapiju, jābūt īpaši sertificētām, lai atpazītu un novērstu DRS un nervu sistēmas toksicitāti. FDA lūdz uzņēmumam veikt pēcreģistrācijas novērošanas pētījumu, iesaistot pacientus, kuri ārstēti ar ciltakabtagene autoleucel, lai novērtētu ilgtermiņa drošību.
CARVYKTI ievada devā 0.5–1.0106 CAR pozitīvas dzīvotspējīgas T-šūnas uz kg ķermeņa svara, maksimālā deva ir 1108 CAR pozitīvas dzīvotspējīgas T-šūnas vienā infūzijā.
