Ukuvulwa kwe-ASH ka-2023 | UDkt. Peihua Lu Uveza i-CAR-T yoPhando lwe-AML oluHlaziyiweyo/oluHlaziyiweyo

Uphononongo lweklinikhi lwesigaba soku-1 lwe-CD7 CAR-T ye-R/R AML olwenziwe liqela likaDaopei Lu e-ASH

INtlanganiso Yonyaka yama-65 ye-American Society of Hematology (ASH) ibanjelwe ngaphandle kwe-intanethi (eSan Diego, e-USA) nakwi-intanethi ngoDisemba 9-12, 2023. Iingcali zethu zenze umboniso omhle wale ngqungquthela, zinegalelo kwiziphumo zophando ezingaphezu kwama-60.

Iziphumo zamva nje ze-"Autologous CD7 CAR-T for relapse/refractory acute myeloid leukemia (R/R AML)", ezixelwe ngomlomo nguNjingalwazi Peihua Lu weSibhedlele saseLudaopei eTshayina, zifumene ingqwalasela eninzi.

Unyango lwe-R/R AML luzisa ingxaki

I-R/R AML ayinaso isiphumo esibi, nokuba isenziwa i-allo-HSCT, kwaye kukho imfuneko engxamisekileyo yezonyango ezintsha. Ngokutsho kukaNjingalwazi uPeihua Lu, ukukhetha okujoliswe kuko kubalulekile ekufuneni unyango olutsha, kwaye malunga ne-30% yezigulane ze-AML zibonisa i-CD7 kwi-leukemoblasts yazo kunye neeseli zomhlaza.

Ngaphambili, iSibhedlele iLu Daopei sixele ukuba izigulane ezingama-60 zisebenzise i-CD7 CAR-T (NS7CAR-T) ekhethiweyo ngokwendalo kunyango lwe-T-cell acute leukemias kunye ne-lymphomas, nto leyo ebonisa ukusebenza kakuhle kunye neprofayili yokhuseleko efanelekileyo. Ukhuseleko kunye nokusebenza kakuhle kokwandiswa kwe-NS7CAR-T kwizigulane ezine-CD7-positive R/R AML kubonwe kwaye kwavavanywa kwisifundo seklinikhi seSigaba sokuQala (NCT04938115) esikhethwe kule Ntlanganiso yoNyaka ye-ASH.

Phakathi kukaJuni 2021 noJanuwari 2023, izigulane ezili-10 ezine-CD7-positive R/R AML (ukubonakaliswa kwe-CD7 >50%) zibhalisiwe kolu phando, zineminyaka ephakathi kwengama-34 (iminyaka esi-7 ukuya kuma-63) Umthwalo ophakathi we-tumor yezigulana ezibhalisiweyo yayiyi-17%, kwaye isigulane esinye sabonakala sinesifo se-diffuse extramedullary disease (EMD). Ixesha eliphakathi ukusuka ekuhlukanisweni kweeseli ukuya ekufakweni kwe-CAR-T cell yayiziintsuku ezili-15, kwaye unyango lotshintsho lwavunyelwa kwizigulana ezinezifo eziwohlokayo ngokukhawuleza ngaphambi kokuba kufakwe i-infusion. Zonke izigulana zafumana i-intravenous fludarabine (30 mg/m2/d) kunye ne-cyclophosphamide (300 mg/m2/d) lymphatic removal chemotherapy iintsuku ezintathu ezilandelelanayo.

Ingcaciso yoMphengululi: Ukuqala kokunciphisa okunzulu

Ngaphambi kokubhaliswa, izigulana zafumana unyango oluphambili oluyi-8 (uluhlu: 3-17). Izigulana ezi-7 zafumana unyango oluphambili oluyi-allogeneic hematopoietic stem cell transplantation (allo-HSCT), kwaye ixesha eliphakathi phakathi kokufakelwa nokubuyela umva yayiziinyanga ezili-12.5 (iinyanga ezi-3.5-19.5). Emva kokufakelwa, incopho ephakathi yeeseli ze-NS7CAR-T ezijikelezayo yayiyiikopi eziyi-2.72×105/μg (0.671~5.41×105 copies/μg) ye-genomic DNA, eyenzeka malunga nosuku lwama-21 (usuku lwe-14 ukuya kusuku lwama-21) ngokwe-q-PCR, kwaye ngomhla we-17 (usuku lwe-11 ukuya kusuku lwama-21) ngokwe-FCM, eyayiyi-64.68% (40.08% ukuya kuma-92.02%).

Umthamo omkhulu wethumba kwizigulana ezibhalise kolu phando wawusondele kwi-73%, kwaye bekukho nenye imeko apho isigulana safumana unyango lwangaphambili oluyi-17, utshilo uNjingalwazi uPeihua Lu. Ubuncinane izigulana ezibini ezafumana i-allo-HSCT zafumana ukuphinda zibuye kwiinyanga ezintandathu emva kokufakelwa utyando. Kucacile ukuba unyango lwezi zigulana luzele "ziingxaki nemiqobo".

Idatha ethembisayo

Emva kweeveki ezine emva kokufakwa kweeseli ze-NS7CAR-T, ezisixhenxe (70%) zifumene i-complement remission (CR) kwi-bone mongo, kwaye ezintandathu zafumana i-CR negative kwi-microscopic residue disease (MRD). Izigulana ezintathu azizange zifumane i-remission (NR), isigulane esinye esine-EMD sibonisa i-partial remission (PR) ngosuku lwama-35 lovavanyo lwe-PET-CT, kwaye zonke izigulana ezine-NR zifunyenwe zilahlekelwe yi-CD7 emva kokulandelela.

Ixesha eliphakathi lokujonga yayiziintsuku ezili-178 (iintsuku ezingama-28 ukuya kwiintsuku ezingama-776). Kwizigulana ezisixhenxe ezifumene i-CR, izigulana ezintathu ezaziphinde zabuyela emva kokufakelwa ngaphambili zafumana i-consolidation yesibini ye-allo-HSCT malunga neenyanga ezi-2 emva kokukhululwa yi-NS7CAR-T cell infusion, kwaye esinye isigulana sahlala singenalo i-leukemia siphila ngomhla wama-401, ngelixa izigulana ezibini ezifakelwe i-osteo-fetal zafa ngenxa yezizathu ezingaphindi zibuyele emva ngomhla wama-241 nowama-776; ezinye izigulana ezine ezingazange zifumane i-consolidation epheleleyo ye-HSCT, izigulana ezi-3 zaphinda zabuyela emva ngomhla wama-47, wama-83, nowama-89, ngokulandelelana (ukulahleka kwe-CD7 kwafunyanwa kuzo zonke izigulana ezintathu), kwaye isigulana esinye safa ngenxa yosulelo lwemiphunga.

Ngokuphathelele ukhuseleko, uninzi lwezigulane (80%) zafumana i-mild cytokine release syndrome (CRS) emva kokufakwa, apho izigulane zebanga lesi-7 I, ibanga loku-1 II, kunye nezigulane ezi-2 (20%) zafumana i-CRS yebanga lesi-3. Akukho zigulane zafumana i-neurotoxicity, kwaye esinye safumana isifo se-mild cutaneous graft-versus-host.

Esi siphumo sibonisa ukuba i-NS7CAR-T isenokuba yindlela ethembisayo yokufikelela kwi-CR yokuqala esebenzayo kwizigulane ezine-CD7-positive R/R AML, nokuba sele zenze iindlela ezininzi zonyango kwangaphambili. Kwaye le ndlela ikwanjalo nakwizigulane eziphinda zibuyele umva emva kwe-allo-HSCT ezineprofayili yokhuseleko elawulekayo.

UNjingalwazi uLu uthe, "Ngedatha esiyifumeneyo ngeli xesha, unyango lwe-CD7 CAR-T lwe-R/R AML lusebenza kakuhle kwaye lunyamezeleka kakuhle kwinqanaba lokuqala, kwaye uninzi lwezigulane lukwazile ukufumana i-CR kunye nokukhululwa okunzulu, okungelula. Kwaye kwizigulane ze-NR okanye izigulane ezibuyele umva, ukulahleka kwe-CD7 yeyona ngxaki iphambili. Ukuze kuvavanywe ngokupheleleyo ukusebenza kwe-NS7CAR-T ekunyangeni i-CD7-positive AML, ukulandelela ngokungathandabuzekiyo kusafuneka kuqinisekiswe ngakumbi ngokufumana idatha engaphezulu kubantu abaninzi abagulayo kunye nexesha elide lokulandelela, kodwa oku kukwanika ithemba elikhulu kunye nokuzithemba kwikliniki."