Unyango lweBrexu-cel CAR-T lubonisa iziphumo ezithembisayo kwizigulane zabantu abadala ezisebenzisa i-R/R B-ALL
I-Brexucabtagene autoleucel (brexu-cel), unyango lweeseli ze-CD19 CAR-T, iye yaba lukhetho olubalulekileyo lonyango lwe-relapse/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) kubantu abadala. Ukwakha kwiziphumo zovavanyo lwe-ZUMA-3, i-brexu-cel ifumene imvume e-United States kwizigulane zabantu abadala ezine-R/R B-ALL. Nangona kunjalo, izifundo zokwenyani zibalulekile ukuqonda ngokupheleleyo ukusebenza kwayo kunye nokhuseleko ekusebenzeni kweklinikhi. Uphononongo olukhulu lwakutshanje olupapashwe kwi Ijenali ye-Clinical Oncology Inika ulwazi oluphambili malunga nokusebenza kwe-brexu-cel kwiqela elikhulu lezigulana, ityhila iziphumo ezikhuthazayo kumanqanaba okukhululwa kunye nokusinda.
Isishwankathelo soFundo
Olu phononongo lweziko ezininzi lubandakanye izigulane ezingama-204 zabantu abadala abane-R/R B-ALL abanyangwa ngaphandle kovavanyo lweklinikhi kumaziko ezonyango angama-31 eMelika. Izigulane ezili-189 zizonke zafumana ngempumelelo i-brexu-cel, kunye nomyinge weendlela ezine zonyango zangaphambili. Phantse isiqingatha sezigulane zazikhe zafumana i-hematopoietic stem cell transplantation (HSCT), ama-59% ayefumene i-blinatumomab, kwaye ama-48% ayenyangwe nge-inotuzumab ozogamicin. Ngexesha le-leukapheresis, ama-42% ezigulane ayekwimeko yokuxolelwa kwe-morphological, into eyayiza kubakhupha kuvavanyo lokuqala lwe-ZUMA-3.
Iziphumo eziphambili
Emva kokulandelelana okuphakathi kweenyanga ezili-11.4, iziphumo zophando zibonise ukusebenza kakuhle kwe-brexu-cel ekunyangeni i-R/R B-ALL:
- Impendulo epheleleyo (CR): Ama-90% ezigulana ezinyangiweyo zifumene impendulo epheleleyo, apho ama-79% abonisa ukukhululwa okuncinci kwesifo esisele (MRD).
- Ukusinda Okungenankqubela-phambili (PFS): I-PFS ephakathi yayiziinyanga ezili-9.5.
- Ukusinda Ngokupheleleyo (OS): I-Median OS ayifikelelwanga, nto leyo ebonisa ukuba isiphumo esinokuba sisigxina ekwandiseni ukusinda kwesigulana.
- Ukungalungi kwe-MRD: Kwizigulane ezihlolwe yi-MRD kusetyenziswa i-clonoSEQ next-generation sequencing, i-MRD negativity ngomhla wama-28 yayinxulunyaniswa nokuphuculwa kwe-PFS kunye ne-OS, nto leyo eyaqinisa ixabiso le-MRD njengesalathisi sokuxela kwangaphambili.
Impembelelo yoNyango lokuHlanganisa
Olu phononongo lufumanise ukuba izigulane ezifumene i-HSCT edibeneyo emva konyango lwe-brexu-cel zine-PFS engcono kakhulu xa kuthelekiswa nezo zingakhange zenze naluphi na unyango lokuqinisa okanye lokugcina. Kuhlalutyo lwe-multivariate, unyango lwe-HSCT (olwenziwa kwizigulane ezingama-30) emva kwe-CAR-T ludibene nomngcipheko oncitshisiweyo kakhulu wokuqhubela phambili kwesifo (HR=0.34).
Iprofayili yoKhuseleko
Nangona lusebenza kakuhle, unyango lwe-brexu-cel lubonise iziganeko ezimbi eziphawulekayo, ezibalulekileyo ekuqwalaselweni kwezonyango:
- I-Cytokine Release Syndrome (CRS) kunye ne-Neurotoxicity (ICANS): I-CRS ibikwe kwi-84% yezigulane, ezineemeko ezinzima (ibanga lesi-3 ukuya kwelesi-4) kwi-11%. I-ICANS yenzekile kwi-56% yezigulane, kunye neemeko ezinzima kwi-31%.
- Ukufa Nokufa Okungabuyeli Ebomini: Amashumi amathathu anesine ekhulwini ezigulana zafa ngexesha lophando, apho i-13% yokufa inganxulumananga nokukhula kwe-leukemia. Izigulana ezilishumi zafa kwiintsuku ezingama-28 zokuqala emva konyango ngenxa yetyhefu okanye usulelo, ingakumbi phakathi kwabo banesifo esiphezulu. Usulelo lwefungus yayiyeyona nto ixhaphakileyo yokufa okunxulumene nosulelo, nto leyo ebonisa imfuneko yokulawula usulelo ngononophelo.
Isiphelo
Iziphumo zolu phononongo lwehlabathi lokwenyani zihambelana neziphumo zovavanyo lwe-ZUMA-3, ziqinisekisa amazinga aphezulu e-brexu-cel e-CR-negative CR kunye neziphumo ezilungileyo zokusinda kwizigulane ezindala ze-R/R B-ALL. Nangona kunjalo, ubuthi obubalulekileyo, ingakumbi i-ICANS enzima kunye nokufa kwangethuba, bugxininisa ukubaluleka kwezicwangciso zokunciphisa umngcipheko, kubandakanya ukuthintela usulelo kunye nokubeka esweni ngokusondeleyo. Ukongeza, ukusetyenziswa konyango oludibeneyo lwe-HSCT emva kwe-CAR-T kuboniswe ukuba kuphucula ukusinda okungenankqubela phambili, okubonelela ngendlela enokwenzeka yokuphucula iziphumo zezigulane.
Olu phononongo lugxininisa indima ye-brexu-cel njengonyango oluqhelekileyo kwi-R/R B-ALL yabantu abadala ngelixa lugxininisa imingeni eqhubekayo ekulawuleni iziphumo zayo ezimbi.