March 2022: Pagkatapos ng apat o higit pang mga naunang linya ng therapy, kabilang ang isang proteasome inhibitor (PI), isang immunomodulatory agent (IMiD), at isang anti-CD38 monoclonal antibody, inaprubahan ng Food and Drug Administration ang ciltacabtagene autoleucel (CARVYKTI, Janssen Biotech, Inc.) para sa paggamot ng mga pasyenteng nasa hustong gulang na may relapsed o refractory multiple myeloma.
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 klinikal na pagsubok that looked at the safety and efficacy of ciltacabtagene autoleucel in 97 patients with relapsed or refractory maramihang myeloma 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 cytokine release syndrome (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.
Ang CARVYKTI ay may isang risk evaluation at mitigation plan na nangangailangan ng mga ospital at klinika na namamahagi ng therapy na partikular na sertipikadong kilalanin at tugunan ang CRS at nervous system toxicities. Hinihiling ng FDA sa kumpanya na magsagawa ng post-marketing observational study na kinasasangkutan ng mga pasyente na ginagamot ng ciltacabtagene autoleucel upang masuri ang pangmatagalang kaligtasan.
Ang CARVYKTI ay ibinibigay sa isang dosis na 0.5-1.0106 CAR-positive viable T-cells bawat kg ng timbang ng katawan, na may maximum na dosis na 1108 CAR-positive viable T-cells bawat pagbubuhos.
