I-Eflornithine ivunywe yi-USFDA kuziguli ezikhulile nezezingane ezine-neuroblastoma eyingozi kakhulu

I-FDA igunyaze eflornithine (IWILFIN, USWM, LLC) ngo-December 13, 2023, ukuze kwehliswe ingozi yokuphinda kwehliswe isifo kubantu abadala kanye nezingane ezine-neuroblastoma (HRNB) enobungozi obukhulu ababenempendulo eyingxenye ku-multiagent yangaphambilini, ukwelashwa kwe-multimodality, okufana ne-anti-GD2 immunotherapy.

Lokhu kuphawula ukugunyazwa kokuqala kwe-FDA kokwelashwa okuklanyelwe ukwehlisa amathuba okuphinda agule ezigulini ezisencane ezine-HRNB.

Ukusebenza kwahlolwa ocwaningweni oluqhathanise imiphumela evela ku-Study 3b (iqembu lokuhlola) no-Study ANBL0032 (iqembu lokulawula langaphandle elikhiqizwe ocwaningweni lomtholampilo). I-Study 3b (NCT02395666) bekuwukuhlola okumaphakathi okuningi obekunelebula evuliwe futhi okungahleliwe, okuhlanganisa amaqoqo amabili. Iziguli ezifanelekile eziyi-105 ezisengozini enkulu i-neuroblastoma kusuka eqenjini elilodwa (i-Stratum 1) banikezwe i-eflornithine ngomlomo, kabili ngosuku ngesilinganiso esinqunywa indawo yomzimba (BSA) kuze kube yilapho isifo siqhubeka, ubuthi obungamukeleki, noma iminyaka engu-2. I-Study 3b yahlelelwa kusengaphambili ukuze iqhathanise imiphumela nesilinganiso somlando sebhentshimakhi yesehlakalo sokusinda kwamahhala (EFS) kusukela kusifundo ANBL0032 njengoba kubikwe ezincwadini ezishicilelwe.

I-Study ANBL0032 bekuwuhlolo olumaphakathi, oluvulekile, olungahleliwe oluqhathanise i-dinutuximab, i-granulocyte-macrophage colony-stimulating factor, interleukin-2, ne-cis-retinoic acid ne-cis-retinoic acid yodwa ezigulini zezingane ezine-neuroblastoma enobungozi obukhulu. Ingalo yokulawula yangaphandle yayisekelwe kudatha evela ezigulini eziyi-1,241 ezingalweni yokuhlola.

Iziguli ezihlangabezane nenqubo yokuqhathanisa phakathi kwe-Study 3b ne-ANBL0032 futhi ezinedatha egcwele yama-covariate athile omtholampilo abhangqwe ngesilinganiso esingu-3:1 ngokusekelwe kuzikolo zabo zokuthambekela. Ukuhlaziywa okuyinhloko kufaka phakathi iziguli ezingama-90 ezelashwe nge-IWILFIN kanye neziguli ezilawulayo ezingama-270 ezivela ku-Study ANBL0032.

Isilinganiso esiyinhloko sokuphumelela kwakuwukusinda ngaphandle kwemicimbi (EFS), okwakuhlanganisa ukuqhubekela phambili kwesifo, ukuphinda, ukonakala kwesibili, noma ukufa nganoma iyiphi imbangela. Enye imethrikhi esebenzayo kwaba ukusinda okuphelele (OS), okwakuchazwa njengokufa kunoma iyiphi imbangela. Isilinganiso sengozi ye-EFS (HR) ekuhlaziyweni okuyinhloko kwakungu-0.48 ngesikhawu sokuzethemba esingu-95% (CI) sika-0.27 kuya ku-0.85. I-OS HR yayingu-0.32 ne-95% CI ka-0.15 kuya ku-0.70. Ngenxa yokungaqiniseki ekulinganiseni umphumela wokwelapha oza nomklamo wocwaningo olawulwa ngaphandle, ukuhlaziya okwengeziwe kwenziwa ekwakhiweni kwabantu abancane noma kusetshenziswa izindlela zezibalo ezihlukile. I-EFS HR ihluka phakathi kuka-0.43 (95% CI: 0.23, 0.79) no-0.59 (95% CI: 0.28, 1.27), kuyilapho i-OS HR isukela ku-0.29 (95% CI: 0.11, 0.72) kuya ku-0.45:95 0.21, 0.98).

Ocwaningweni 3b, imiphumela engemihle evame kakhulu (≥5%), ehlanganisa nokungahambi kahle kwelebhu, kwaba ikhala elivalekile, isifo sohudo, ukukhwehlela, i-sinusitis, inyumoniya, ukutheleleka komgudu wokuphefumula ongenhla, i-conjunctivitis, ukuhlanza, imfiva, i-rhinitis eguquguqukayo, ama-neutrophils aphansi, i-ALT ephezulu ne-AST, ukulahlekelwa ukuzwa, ukutheleleka kwesikhumba, kanye nokutheleleka komgudu womchamo.