Unyango lwe-CAR-T Loyisa Ukuqikelela Okubi kwi-B-Cell Lymphoma ePhakamileyo
Uphononongo lwakutshanje olupapashwe kwi Ukuqhubela phambili kwegaziityhila ukuba unyango lweeseli ze-CAR-T lubonelela ngeenzuzo ezibalulekileyo zeklinikhi kwizigulana ezinezinga eliphezulu I-B-Cell Lymphoma (HGBL), uhlobo olunobundlongondlongo kakhulu lwe-large B-cell lymphoma (LBCL). Uphononongo lwe-DESCAR-T LYSA, olwenziwe ngabaphandi baseFransi, lugxile kwizigulana ezifumene unyango lwe-CAR-T njengonyango lwesithathu okanye ngaphaya koko, kuquka abo bane-MYC kunye ne-BCL2 kunye/okanye i-BCL6 rearrangements—eyaziwa ngokuba yi-“double-hit” okanye “triple-hit” lymphoma.
Olu phononongo lubhalise izigulane ezingama-228 ezivela kwirejista ye-DESCAR-T yaseFransi, apho ezingama-73 kuzo zafunyaniswa zine-HGBL, ngelixa ezinye ezili-155 zazine-LBCL engekho phantsi kwe-HGBL. Olu phononongo lujolise ekuvavanyeni ukhuseleko kunye nokusebenza kakuhle konyango lwe-CAR-T kula maqela, kunye nexesha eliphakathi lokulandelela leenyanga ezili-18.5.
Iziphumo zityhile ukuba amazinga empendulo iyonke (ORR) kunye namazinga empendulo epheleleyo (CR) ayethelekiswa phakathi kwezigulane ze-HGBL kunye nezingengo-HGBL, kwi-68% kunye ne-60% kwi-HGBL, kunye ne-76% kunye ne-59% kwizigulana ezingezizo i-HGBL, ngokulandelelana (p=0.293 kunye ne-p=0.923). Ngaphezu koko, i-median progression-free survival (PFS) kwizigulana ze-HGBL yayiyiinyanga ezi-3.2, xa kuthelekiswa neenyanga ezi-4.5 kwizigulana ezingezizo i-HGBL, nangona lo mahluko wawungabalulekanga ngokwezibalo (p=0.103). Ngokufanayo, i-median overeal survival (OS) yayiyiinyanga ezili-15.4 kwizigulana ze-HGBL xa kuthelekiswa neenyanga ezili-18.3 kwizigulana ezingezizo i-HGBL (p=0.214).
Okunomdla kukuba, xa i-OS yayibalwa ukususela ngomhla izigulana ezazifanelekela unyango lwe-CAR-T, i-OS ephakathi kwizigulana ze-HGBL yehla yaya kwiinyanga eziyi-7.6, xa ithelekiswa neenyanga ezili-11.8 kwizigulana ezingezizo ze-HGBL (p=0.062), nto leyo ebonisa ukuba ixesha lolawulo lwe-CAR-T lidlala indima ebalulekileyo ekuphuculeni iziphumo.
Phakathi kweentlobo ezahlukeneyo ze-HGBL, abo bane-MYC-BCL2 double-hit lymphoma babeneziphumo ezimbi kakhulu, kunye ne-OS ephakathi yeenyanga eziyi-6.6 kuphela, ephantsi kakhulu kunezinye iintlobo ze-HGBL (HGBL-DH MYC-BCL6: iinyanga ezili-13.6, HGBL-NOS: iinyanga ezili-18.5) kunye nezigulane ezingezizo ze-HGBL (iinyanga ezili-11.8). Nangona kunjalo, akukho mahluko ubalulekileyo kwi-OS okanye kwi-PFS ofunyenweyo xa kuthelekiswa ixesha lokufakwa kwe-CAR-T.
Ukhuseleko lonyango lwe-CAR-T beluhambelana kuzo zombini amaqela e-HGBL kunye namaqela angengawo e-HGBL. Ukuvela kwe-cytokine release syndrome (CRS) kunye ne-immune effector cell-associated neurotoxicity syndrome (ICANS) bekufana phakathi kwamaqela amabini. Nangona kunjalo, ama-38% ezigulana ze-HGBL zazifuna ukhathalelo lwe-ICU kwi-CRS, nangona oku kufana neemfuno zonyango ezibonwa kwizigulana ezingengazo eze-HGBL.
Uphononongo lwe-DESCAR-T LYSA lubonisa amandla onyango lwe-CAR-T ekuphuculeni ukubikezela kwezigulane ezine-HGBL, nokuba kukwimigca yonyango yamva nje. Nangona i-CAR-T isenokungayoyisi ngokupheleleyo i-prognosis embi enxulunyaniswa nezinye iintlobo ezinobungozi obukhulu, ezifana ne-HGBL ephindwe kabini, olu phononongo lukhuthaza ukungenelela kwangoko ngonyango lwe-CAR-T, olunokubonelela ngeziphumo ezingcono zokusinda. Ngaphezu koko, ukunciphisa ixesha phakathi kwe-leukapheresis kunye nokufakwa kwe-CAR-T kunokuba yinto ebalulekileyo kwizigulane ezinezifo eziqatha ezifana ne-HGBL.
Olu phando lugxininisa ukubaluleka konyango lwe-CAR-T njengonyango olusebenzayo kwi-B-cell lymphoma ekumgangatho ophezulu kwaye lubonelela ngengqiqo ebalulekileyo yokuphucula amaxesha onyango ukuze kubekho iziphumo ezingcono zesigulana. Izifundo ezongezelelweyo ziyafuneka ukuze kuhlolwe iindlela zokuphucula ukusebenza kakuhle konyango lwe-CAR-T, ngakumbi kwiintlobo ze-lymphoma ezinzima.