Lifileucel je odobril USFDA za neoperabilen ali metastatski melanom

Uprava za hrano in zdravila je izdala pospešeno odobritev lifilevcel (Amtagvi, Iovance Biotherapeutics, Inc.) dne 16. februarja 2024. Ta odobritev je namenjena odraslim bolnikom z neoperabilnim ali metastatskim melanomom, ki so bili predhodno zdravljeni s protitelesi za blokiranje PD-1. Poleg tega morajo biti bolniki pozitivni na BRAF V600 in so prejeli zaviralec BRAF z zaviralcem MEK ali brez njega.

An open-label, single-arm trial was conducted globally across multiple centers and cohorts to assess the safety and effectiveness in patients with unresectable or metastatic melanoma. These patients had received prior treatment with at least one systemic therapy, which included a PD-1 blocking antibody. If they tested positive for the BRAF V600 mutation, they had also been treated with a BRAF inhibitor, with or without a MEK inhibitor. Out of 89 patients who were given lifileucel, two were omitted because the product did not fulfill specifications and five were excluded owing to product comparability. Lifileucel was given after a lymphodepleting treatment regimen which included cyclophosphamide at a dose of 60 mg/kg daily with mesna for 2 days, followed by fludarabine at a dose of 25 mg/m2 daily for 5 days. Patients were administered IL-2 (aldesleukin) at a dosage of 600,000 IU/kg every 8 to 12 hours for up to 6 doses between 3 to 24 hours after infusion to promote cell growth in vivo. The median dose of lifileucel delivered was 21.1× 109 viable cells. The median number of IL-2 (aldesleukin) doses delivered was 6.

Primarne metrike učinkovitosti so bile objektivna stopnja odziva (ORR) in trajanje odziva (DoR). Mediani čas začetne reakcije na lifileucel je bil 1.5 meseca. Študija ORR je vključevala 73 udeležencev, ki so prejemali lifileucel v predpisanem razponu odmerkov od 7.5 x 109 do 72 x 109 živih celic. Objektivna stopnja odziva (ORR) je bila 31.5 % s 95-odstotnim intervalom zaupanja (CI) od 21.1 % do 43.4 %, mediana trajanja odziva (DoR) pa ni bila dosežena (NR) s 95-odstotnim intervalom zaupanja 4.1 meseca do št.

Gradivo za predpisovanje vključuje opozorilo v okvirju za smrt, povezano z zdravljenjem, dolgotrajno hudo citopenijo, hudo okužbo, težave s srcem in okvaro ledvic. Najpogostejši neželeni učinki (≥20 %) v padajočem vrstnem redu pojavljanja so bili mrzlica, pireksija, utrujenost, tahikardija, driska, febrilna nevtropenija, edem, izpuščaj, hipotenzija, alopecija, okužba, hipoksija in dispneja.

Predlagani odmerek lifileucela se giblje od 7.5 x 10^9 do 72 x 10^9 živih celic.