I-Lifileucel igunyazwe yi-USFDA ngemelanoma engasabukeki noma ye-metastatic

I-Food and Drug Administration inikeze imvume esheshisiwe lifileucel (Amtagvi, Iovance Biotherapeutics, Inc.) ngomhla ka-Febhruwari 16, 2024. Lokhu kugunyazwa okweziguli ezikhulile ezinemelanoma engahlanjululwa noma ye-metastatic ezike zelashwa ngaphambilini nge-PD-1 evimba amasosha omzimba. Ukwengeza, iziguli kufanele zibe ne-BRAF V600 positive futhi zithole i-BRAF inhibitor ene-MEK inhibitor noma ngaphandle kwayo.

Uhlolo lwelebula evulekile, olungalo olulodwa lwenziwa emhlabeni wonke ezikhungweni eziningi namaqoqo ukuze kuhlolwe ukuphepha nokusebenza ezigulini ezinokungahoxiki noma ezine-metastatic. melanoma. Lezi ziguli zazithole ukwelashwa kwangaphambili okungenani ngokwelashwa okuhleliwe okukodwa, okuhlanganisa ne-PD-1 evimba amasosha omzimba. Uma kutholakala ukuthi bane-HIV yokuguqulwa kwe-BRAF V600, babephinde belashwe nge-BRAF inhibitor, nge-MEK inhibitor noma ngaphandle kwayo. Ezigulini ezingama-89 ezinikezwe i-lifileucel, ezimbili azizange zifakwe ngenxa yokuthi umkhiqizo awuzange ufeze okucacisiwe futhi ezinhlanu azifakwanga ngenxa yokuqhathaniswa komkhiqizo. I-Lifileucel yanikezwa ngemva kohlobo lokwelapha oluqeda i-lymphophosphamide ngethamo lika-60 mg/kg ngosuku nge-mesna izinsuku ezi-2, kulandele i-fludarabine ngethamo lika-25 mg/m2 nsuku zonke izinsuku ezi-5. Iziguli zanikezwa i-IL-2 (aldesleukin) ngethamo lika-600,000 IU/kg njalo emahoreni ayi-8 kuye kwayi-12 kuze kufike kumithamo emi-6 phakathi kwamahora ama-3 kuye kwangama-24 ngemuva kokumnika ukukhuthaza ukukhula kweseli ku-vivo. Umthamo omaphakathi we-lifileucel olethiwe wawungamaseli asebenzayo angama-21.1 × 109. Inombolo emaphakathi yemithamo ye-IL-2 (aldesleukin) ethunyelwe yayingu-6.

Amamethrikhi okusebenza ayinhloko kwakuyizinga lokuphendula lenhloso (ORR) kanye nobude besikhathi sokuphendula (DoR). Isikhathi esimaphakathi sokusabela kokuqala ku-lifileucel kwakuyizinyanga eziyi-1.5. Ucwaningo lwe-ORR lufake abahlanganyeli abangama-73 abanikezwe i-lifileucel ngaphakathi kwebanga lemithamo elinqunyiwe lamaseli asebenzayo angama-7.5 x109 kuya ku-72×109. Izinga lokuphendula lenhloso (ORR) lalingu-31.5% kanye nesikhawu sokuzithemba esingu-95% (CI) sika-21.1% kuya ku-43.4%, kanti ubude besikhathi sokuphendula (DoR) asifinyelelwanga (NR) nge-95% CI yezinyanga ezingu-4.1 I-NR.

Izinto ezinqumayo zihlanganisa Isexwayiso Esinebhokisi sokufa okuhlobene nokwelashwa, i-cytopenia eqinile eqinile, ukutheleleka okunzima, izinkinga zenhliziyo, nokukhubazeka kwezinso. Imiphumela emibi evame kakhulu (≥20%) ekwehleni kokwenzeka kwaba ukugodola, i-pyrexia, ukukhathala, i-tachycardia, isifo sohudo, i-febrile neutropenia, i-edema, ukuqubuka, i-hypotension, i-alopecia, ukutheleleka, i-hypoxia, ne-dyspnea.

Umthamo ophakanyisiwe we-lifileucel usukela ku-7.5 x 10^9 kuya ku-72 x 10^9 amaseli asebenzayo.