Ukwelashwa kwe-CAR-T Kunqoba Ukubikezela Okubi ku-Lymphoma Ye-B-Cell Esezingeni Eliphezulu
Ucwaningo lwamuva nje olushicilelwe ku- Ukuthuthuka Kwegazikwembula ukuthi ukwelashwa ngamaseli e-CAR-T kunikeza izinzuzo ezibalulekile zezokwelapha ezigulini ezinezinga eliphezulu I-B-Cell Lymphoma (HGBL), uhlobo olunamandla kakhulu lwe-large B-cell lymphoma (LBCL). Ucwaningo lwe-DESCAR-T LYSA, olwenziwe abacwaningi baseFrance, lugxile ezigulini ezithole ukwelashwa kwe-CAR-T njengokwelashwa komugqa wesithathu noma ngaphezulu, kufaka phakathi lezo ezine-MYC kanye ne-BCL2 kanye/noma i-BCL6 rearrangements—ezaziwa ngokuthi i-“double-hit” noma i-“triple-hit” lymphoma.
Ucwaningo lubhalise iziguli ezingu-228 ezivela ku-French DESCAR-T registry, ezingu-73 zazo zatholakala zine-HGBL, kanti ezinye ezingu-155 zazine-LBCL engeyona i-HGBL. Ucwaningo luhlose ukuhlola ukuphepha nokusebenza kahle kokwelashwa kwe-CAR-T kula maqembu, ngesikhathi sokulandelela esimaphakathi sezinyanga ezingu-18.5.
Okutholakele kwembule ukuthi amazinga okuphendula jikelele (ORR) kanye namazinga okuphendula okuphelele (CR) ayefana phakathi kweziguli ze-HGBL kanye nezingezona eze-HGBL, ku-68% kanye no-60% we-HGBL, kanye no-76% kanye no-59% kwabangebona abe-HGBL, ngokulandelana (p=0.293 kanye no-p=0.923). Ngaphezu kwalokho, ukusinda okuphakathi nendawo okungenalo inqubekela phambili (PFS) kweziguli ze-HGBL kwakuyizinyanga ezingu-3.2, uma kuqhathaniswa nezinyanga ezingu-4.5 kweziguli ezingezona eze-HGBL, yize lo mehluko wawungabalulekile ngokwezibalo (p=0.103). Ngokufanayo, ukusinda okuphakathi nendawo (OS) kwakuyizinyanga ezingu-15.4 kweziguli ze-HGBL uma kuqhathaniswa nezinyanga ezingu-18.3 kweziguli ezingezona eze-HGBL (p=0.214).
Ngokuthakazelisayo, lapho i-OS ibalwa kusukela ngosuku iziguli ezifanelekela ukwelashwa kwe-CAR-T, i-OS ephakathi nendawo yeziguli ze-HGBL yehle yaya ezinyangeni ezingu-7.6, uma kuqhathaniswa nezinyanga ezingu-11.8 zeziguli ezingezona eze-HGBL (p=0.062), okubonisa ukuthi isikhathi sokuphathwa kwe-CAR-T sidlala indima ebalulekile ekuthuthukiseni imiphumela.
Phakathi kwezinhlobo ezahlukene ze-HGBL, labo abane-MYC-BCL2 double-hit lymphoma babe nemiphumela emibi kakhulu, nge-OS ephakathi yezinyanga ezingu-6.6 kuphela, ephansi kakhulu kunezinye izinhlobo ze-HGBL (HGBL-DH MYC-BCL6: izinyanga ezingu-13.6, HGBL-NOS: izinyanga ezingu-18.5) kanye neziguli ezingezona eze-HGBL (izinyanga ezingu-11.8). Naphezu kwalokhu, akukho mehluko obalulekile ku-OS noma ku-PFS otholakale lapho kuqhathaniswa isikhathi sokufakwa kwe-CAR-T.
Ukuphepha kokwelashwa kwe-CAR-T bekufana kuwo womabili amaqembu e-HGBL kanye namaqembu angewona awe-HGBL. Ukuvela kwe-cytokine release syndrome (CRS) kanye ne-immune effector cell-associated neurotoxicity syndrome (ICANS) bekufana phakathi kwamaqembu amabili. Kodwa-ke, ama-38% eziguli ze-HGBL ayedinga ukunakekelwa kwe-ICU kwe-CRS, yize lokhu kwakufana nezidingo zokwelapha ezibonwa ezigulini ezingewona awe-HGBL.
Ucwaningo lwe-DESCAR-T LYSA luqokomisa amandla okwelashwa kwe-CAR-T ekuthuthukiseni ukubikezela kweziguli ezine-HGBL, ngisho nasezindleleni zakamuva zokwelashwa. Nakuba i-CAR-T ingase ingakunqobi ngokuphelele ukubikezela okubi okuhlobene nezinhlobo ezithile eziyingozi kakhulu, njenge-HGBL ephindwe kabili, ucwaningo lukhuthaza ukungenelela kusenesikhathi ngokwelashwa kwe-CAR-T, okungase kunikeze imiphumela engcono yokusinda. Ngaphezu kwalokho, ukunciphisa isikhathi phakathi kwe-leukapheresis kanye nokufakwa kwe-CAR-T kungaba yinto ebalulekile ezigulini ezinesifo esinamandla njenge-HGBL.
Lolu cwaningo lugcizelela ukubaluleka kokwelashwa kwe-CAR-T njengokwelashwa okuphumelelayo kwe-B-cell lymphoma esezingeni eliphezulu futhi lunikeza ukuqonda okubalulekile ekwenzeni ngcono isikhathi sokwelashwa ukuze kube nemiphumela engcono yesiguli. Kudingeka izifundo ezengeziwe ukuze kuhlolwe izindlela zokuthuthukisa ukusebenza kahle kokwelashwa kwe-CAR-T, ikakhulukazi ezinhlotsheni ze-lymphoma eziyinselele.