Ukungenelela Kwasekuqaleni Ngokwelashwa Kwe-CAR-T Kwe-B-Cell Lymphoma Enkulu Kubonisa Imiphumela Ethembisayo
Ucwaningo lwamuva nje olushicilelwe ku- Ukufakelwa Komnkantsha Wamathambobahlole ukusebenza kahle kokungenelela kusenesikhathi uma kuqhathaniswa nokwelashwa kweseli le-CAR-T ezigulini ezinezinkinga ezinkulu zempilo yengqondo. I-B-Cell Lymphoma (LBCL). Lwenziwe ezikhungweni ezintathu e-US nase-Israel, lolu cwaningo luhilele iziguli ezingu-354 ezelashwe ngokwelashwa kwe-CAR-T okuqondiswe ku-CD19 phakathi kuka-Ephreli 2016 noMashi 2024. Lolu cwaningo luhlose ukuhlola umthelela wokunikeza ukwelashwa kwe-CAR-T njengokwelashwa komugqa wesibili (ukwelashwa kwasekuqaleni) uma kuqhathaniswa nokwelashwa komugqa wesithathu noma kamuva (ukwelashwa sekwephuzile) kwe-LBCL ephinde yabuya noma engaphenduli.
Imiphumela ikhombisile ukuthi ukunikezwa kokuqala kokwelashwa kwe-CAR-T, uma kunikezwa ngenkathi umthwalo wesimila sesiguli uphansi futhi indawo yokuzivikela yomzimba ingcono, kwaba nemiphumela ethembisayo. Izinga lokuphendula eliphelele ngemva konyaka owodwa lalingu-87% ekwelashweni kwasekuqaleni kanye no-82% ekwelashweni kwasemuva, yize umehluko wawungabalulekile ngokwezibalo (p=0.3). Kodwa-ke, izinga lokusinda lilonke (OS) laliphezulu eqenjini lokwelashwa kwasekuqaleni, kanye nokusinda okungu-82% ngonyaka owodwa uma kuqhathaniswa no-71% eqenjini lokwelashwa kwasemuva (p=0.048).
Ngokuthakazelisayo, lolu cwaningo aluzange luthole umehluko omkhulu phakathi kwamaqembu amabili ekusindeni okungenakho ukuqhubeka (PFS), amazinga okubuyela emuva, noma ukufa okuhlobene nokwelashwa. Amazinga okubuyela emuva konyaka owodwa ayengu-37% eqenjini lokuqala kanye no-43% eqenjini eliphelile, ngaphandle komthelela omkhulu kusukela esikhathini sokuphathwa kwe-CAR-T (p=0.2). Lolu cwaningo luphinde lwathola ukuthi ukwanda kwe-cytokine release syndrome (CRS) yebanga lesi-2 noma ngaphezulu kwakuphansi kakhulu eqenjini lokwelashwa kokuqala (26%) uma kuqhathaniswa neqembu lokwelashwa sekwephuzile (39%) (p=0.031), okuphakamisa ukuthi ukungenelela kwangaphambilini kunganciphisa ubuthi obuthile obuhlobene nokwelashwa.
Lokhu okutholakele kusekela ukusetshenziswa kokwelashwa kwe-CAR-T njengokwelashwa kwesibili kwe-LBCL, njengoba kungavimbela izinkinga ezihlobene nokwelashwa kwesigaba esilandelayo, okuhlanganisa nokubekezelelana okuncishisiwe ngenxa yempilo yesiguli iyonke noma ukukhathala kwamaseli e-T. Ucwaningo luphinde lugcizelele isidingo socwaningo olwengeziwe lokuqonda izindlela zebhayoloji zokumelana ne-CAR-T kanye nokuhlola izindlela zokwelapha ezihlanganisiwe ezingaba khona ukuze kuthuthukiswe imiphumela kuzo zonke izigaba zokwelashwa.
Nakuba ucwaningo lubheka emuva futhi lungase lube nobandlululo kanye nokulandelela okulinganiselwe, imiphumela inikeza ukuqonda okubalulekile ngesikhathi esifanele sokwelashwa kwe-CAR-T ezigulini ze-LBCL. Okutholakele kusikisela ukuthi ukungenelela kusenesikhathi ngokwelashwa kwe-CAR-T kungathuthukisa ukusinda futhi kunciphise ubuthi, kunikeze isinyathelo esibalulekile ekuthuthukiseni amasu okwelapha lo mdlavuza onzima.