Ukwelashwa kwe-Brexu-cel CAR-T Kubonisa Imiphumela Ethembisayo Ezigulini Ezigulayo Ezigulayo Nezigulayo Zabantu Abadala

I-Brexucabtagene autoleucel (i-brexu-cel), ukwelashwa kwamaseli e-CD19 CAR-T, isibe yindlela yokwelapha ebalulekile ye-relapse/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) kubantu abadala. Ngokwakhela emiphumeleni yesilingo se-ZUMA-3, i-brexu-cel yamukelwa e-United States ezigulini zabantu abadala ezine-R/R B-ALL. Kodwa-ke, izifundo zangempela zibalulekile ukuze kuqondwe ngokugcwele ukusebenza kwayo kanye nokuphepha kwayo emtholampilo. Ucwaningo olukhulu lwamuva nje olushicilelwe ku- Ijenali ye-Clinical Oncology inikeza ukuqonda okubalulekile ngokusebenza kwe-brexu-cel kulo lonke iqembu leziguli, kwembula imiphumela ekhuthazayo emazingeni okuphumula kanye nokusinda.

Ukubuka Konke Kwesifundo

Lolu cwaningo oluhlanganisa izikhungo eziningi luhilele iziguli ezindala ezingu-204 ezine-R/R B-ALL ezelashwa ngaphandle kwezivivinyo zemitholampilo ezikhungweni zezokwelapha ezingu-31 e-United States. Iziguli ezingu-189 sezizonke zathola i-brexu-cel ngempumelelo, kanye nesilinganiso semigqa emine yokwelashwa yangaphambili. Cishe ingxenye yeziguli yayike yafakwa i-hematopoietic stem cell transplantation (HSCT), u-59% wayethole i-blinatumomab, kanti u-48% wayelashwe nge-inotuzumab ozogamicin. Ngesikhathi se-leukapheresis, u-42% weziguli wayesekukhululweni kwesimo somzimba, okuyisici esasizozikhipha esivivinyweni sokuqala se-ZUMA-3.

Okutholakele Okubalulekile

Ngemva kokulandelela okuphakathi kwezinyanga ezingu-11.4, imiphumela yocwaningo ibonise ukusebenza kahle okukhulu kwe-brexu-cel ekwelapheni i-R/R B-ALL:

• Impendulo Ephelele (CR): Ama-90% eziguli ezelashwe athole impendulo ephelele, kanti ama-79% abonise ukukhululeka okuncane kwesifo esisele (MRD).
• Ukusinda Okungenanqubekela-Phambili (PFS): Isilinganiso se-PFS sasiyizinyanga ezingu-9.5.
• Ukusinda Okuphelele (OS): I-Median OS ayifinyelelwanga, okuphakamisa umphumela ohlala isikhathi eside ekwandiseni ukusinda kwesiguli.
• Ukungalungi kwe-MRD: Ezigulini ezihlolwe i-MRD kusetshenziswa i-clonoSEQ next-generation sequencing, ukunganaki kwe-MRD ngosuku lwama-28 kwahlotshaniswa ne-PFS kanye ne-OS ethuthukisiwe, okuqinisa inani le-MRD njengesibonakaliso sokubikezela.

Umthelela Wokwelashwa Kokuhlanganisa

Ucwaningo luphinde lwathola ukuthi iziguli ezithole i-HSCT ehlanganisiwe ngemuva kokwelashwa nge-brexu-cel zazine-PFS engcono kakhulu uma kuqhathaniswa nalezo ezingazange zithole noma yiluphi ukwelashwa kokuqinisa noma kokulondoloza. Ekuhlaziyweni kwe-multivariate, ukwelashwa kwe-HSCT (okwenziwa ezigulini ezingu-30) ngemva kwe-CAR-T kwakuhlotshaniswa nengozi encishisiwe kakhulu yokuqhubeka kwesifo (HR=0.34).

Iphrofayili Yokuphepha

Naphezu kokusebenza kwayo kahle, ukwelashwa kwe-brexu-cel kube nemiphumela emibi ephawulekayo, okuyizinto ezibalulekile ekuphathweni kwezokwelapha:

• I-Cytokine Release Syndrome (CRS) kanye ne-Neurotoxicity (ICANS): I-CRS ibikwe ku-84% weziguli, ezinezimo ezimbi kakhulu (ibanga lesi-3-4) ku-11%. I-ICANS yenzeka ku-56% weziguli, kanti nezimo ezimbi kakhulu ku-31%.
• Ukufa Nokungaphinde Kubuye: Amaphesenti angamashumi amathathu nane eziguli ashone ngesikhathi socwaningo, kanti u-13% wokufa awuhlobene nokuqhubeka kwe-leukemia. Iziguli eziyishumi zashona zingakapheli izinsuku ezingu-28 zokuqala ngemva kokwelashwa ngenxa yobuthi noma ukutheleleka, ikakhulukazi kulabo abanomthwalo omkhulu wezifo. Ukutheleleka ngefungus kwakuyimbangela evame kakhulu yokufa okuhlobene nokutheleleka, okubonisa isidingo sokuphathwa kokutheleleka okuqaphile.

Isiphetho

Okutholakele kulolu cwaningo lwangempela kuvumelana nemiphumela yesilingo se-ZUMA-3, okuqinisekisa amazinga aphezulu e-brexu-cel e-CR engenayo i-MRD kanye nemiphumela emihle yokusinda kweziguli ezindala ze-R/R B-ALL. Kodwa-ke, ubuthi obukhulu, ikakhulukazi i-ICANS enzima kanye nokufa kwasekuqaleni, kugcizelela ukubaluleka kwamasu okunciphisa ubungozi, okuhlanganisa ukuvimbela ukutheleleka kanye nokuqapha eduze. Ngaphezu kwalokho, ukusetshenziswa kokwelashwa okuhlanganisiwe kwe-HSCT ngemuva kwe-CAR-T kuboniswe ukuthi kuthuthukisa ukusinda okungenalo ukuqhubekela phambili, okunikeza indlela engaba khona yokwenza ngcono imiphumela yeziguli.

Lolu cwaningo lugcizelela indima ye-brexu-cel njengokwelashwa okujwayelekile ku-R/R B-ALL yabantu abadala ngenkathi kugcizelelwa izinselele eziqhubekayo ekuphatheni imiphumela yayo emibi.