Lifileucel probatur ab USFDA pro melanoma irresectibili vel metastatico

Cibus et medicamentis Administration dari accelerato approbatione lifileucel (Amtagvi, Iovance Biotherapeutics, Inc.) die 16 mensis Februarii anno 2024. Haec approbatio aegrotis adultis cum melanoma irresectabili vel metastatico, qui antea cum anticorpore PD-1 interclusione tractati sunt. Praeterea aegros BRAF V600 positivus esse oportet et inhibitorem MEK inhibitorem vel sine BRAF accepisse.

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.

Primaria efficacia metrica erant responsio obiectiva rate (ORR) et duratio responsionis (DoR). Medium tempus ad initialem reactionem ad lifileucel erat 1.5 menses. ORR studium includitur 73 participes qui lifileucel administrabantur intra dosis praescriptam latitudinem 7.5 x109 ad 72×109 cellulas viabiles. Ratus responsionis obiectiva (ORR) erat 31.5% cum intervallo fiduciae 95% (CI) 21.1% ad 43.4%, et mediana periodus responsionis (NR) cum 95% CI mensis ad 4.1 pervenerat. NR.

Materia praescripta includit Monitum inclusum ad mortem curationis relatam, gravem cytopenia, gravem contagionem, quaestiones cardiacas, et renum detrimentum. Frequentiores effectus adversae (≥20%) in ordine descendendo eventi erant frigora, pyrexia, languor, tachycardia, fluxus ventris, febrilis neutropenia, OEDEMA, temeraria, hypotension, alopecia, contagio, hypoxia, dyspnoea.

Moles dosis lifileucelis suggessit ab 7.5 x 10^9 ad 72 x 10^9 cellulis viables.