Ukuvulwa kwe-ASH ka-2023 | UDkt. Peihua Lu Wethula i-CAR-T Yocwaningo lwe-AML oluphindaphindekile/oluphikisayo

Ucwaningo lwezokwelapha lwesigaba sokuqala lwe-CD7 CAR-T ye-R/R AML olwenziwe yiqembu likaDaopei Lu e-ASH

Umhlangano Waminyaka Yonke Wama-65 we-American Society of Hematology (ASH) ubanjelwe ngaphandle kwe-inthanethi (eSan Diego, e-USA) kanye naku-inthanethi ngoDisemba 9-12, 2023. Izazi zethu zenze umbukiso omuhle kakhulu walo mhlangano, zanikela ngemiphumela yocwaningo engaphezu kuka-60.

Imiphumela yakamuva ye-"Autologous CD7 CAR-T ye-relapse/refractory acute myeloid leukemia (R/R AML)", ebikwe ngomlomo nguSolwazi Peihua Lu waseLudaopei Hospital eShayina, ithole ukunakwa okukhulu.

Ukwelashwa kwe-R/R AML kuveza inkinga

I-R/R AML inesimo esibi sokubikezela, ngisho nalapho ifakwa i-allogeneic hematopoietic stem cell transplantation (allo-HSCT), futhi kunesidingo esiphuthumayo sezokwelapha sezinketho ezintsha zokwelapha. Ngokusho kukaSolwazi Peihua Lu, ukukhetha okuqondiwe kubalulekile ekufuneni izindlela zokwelapha ezintsha, futhi cishe ama-30% eziguli ze-AML aveza i-CD7 kuma-leukemoblast azo kanye namaseli okuzala abulalayo.

Ngaphambilini, iSibhedlela iLu Daopei sibike iziguli ezingu-60 ezisebenzise i-CD7 CAR-T (NS7CAR-T) ekhethiwe ngokwemvelo ekwelapheni i-T-cell acute leukemias kanye ne-lymphomas, okubonisa ukusebenza kahle okukhulu kanye nephrofayili yokuphepha enhle. Ukuphepha kanye nokusebenza kahle kokwanda kwe-NS7CAR-T ezigulini ezine-CD7-positive R/R AML kwabonwa futhi kwahlolwa ocwaningweni lwezokwelapha lweSigaba I (NCT04938115) olukhethwe kulo Mhlangano Waminyaka Yonke we-ASH.

Phakathi kukaJuni 2021 noJanuwari 2023, iziguli eziyi-10 ezine-CD7-positive R/R AML (ukubonakaliswa kwe-CD7 >50%) zabhaliswa kulolu cwaningo, zineminyaka ephakathi kwengu-34 (iminyaka engu-7 - 63) Umthwalo wesimila ophakathi weziguli ezibhalisiwe wawungu-17%, kanti isiguli esisodwa savezwa yisifo se-diffuse extramedullary (EMD). Isikhathi esimaphakathi kusukela ekuhlukanisweni kweseli kuya ekufakweni kweseli le-CAR-T sasiyizinsuku ezingu-15, kanti ukwelashwa kokuguquka kwavunyelwa ezigulini ezinezifo eziwohloka ngokushesha ngaphambi kokuba kufakwe. Zonke iziguli zathola i-intravenous fludarabine (30 mg/m2/d) kanye ne-cyclophosphamide (300 mg/m2/d) lymphatic removal chemotherapy izinsuku ezintathu zilandelana.

Ukuhumusha Komcwaningi: Ukuqala Kokunciphisa Okujulile

Ngaphambi kokubhaliswa, iziguli zathola ukwelashwa okuphambili okungu-8 (ububanzi: 3-17). Iziguli ezingu-7 zazithole ukwelashwa kwe-allogeneic hematopoietic stem cell (allo-HSCT), kanti isikhathi esiphakathi phakathi kokufakelwa nokubuyela emuva kwakuyizinyanga ezingu-12.5 (izinyanga ezingu-3.5-19.5). Ngemva kokufakwa, inani eliphakeme eliphakathi lamaseli e-NS7CAR-T ajikelezayo lalingamakhophi angu-2.72×105/μg (amakhophi angu-0.671~5.41×105/μg) we-genomic DNA, okwenzeka cishe ngosuku lwama-21 (usuku lwe-14 kuya kosuku lwama-21) ngokusho kwe-q-PCR, kanye nangosuku lwe-17 (usuku lwe-11 kuya kosuku lwama-21) ngokusho kwe-FCM, okwakungu-64.68% (40.08% kuya ku-92.02%).

Umthamo omkhulu kakhulu wesimila seziguli ezibhalise kulolu cwaningo wawucishe ube ngu-73%, futhi kwaba necala elilodwa lapho isiguli sathola khona ukwelashwa okungu-17 ngaphambilini, kusho uSolwazi Peihua Lu. Okungenani iziguli ezimbili ezathola ukwelashwa kwe-allo-HSCT zaphinde zabhekana nokubuyela kwesifo phakathi nezinyanga eziyisithupha zokufakelwa. Kusobala ukuthi ukwelashwa kwalezi ziguli kugcwele "ubunzima nezithiyo".

Idatha ethembisayo

Emasontweni amane ngemuva kokufakwa kweseli le-NS7CAR-T, eziyisikhombisa (70%) zithole ukuxolelwa okuphelele (CR) emnkantsheni wethambo, kanti eziyisithupha zithole i-CR negative ngenxa yesifo esisele se-microscopic (MRD). Iziguli ezintathu azizange zithole ukuxolelwa (NR), kanti isiguli esisodwa esine-EMD sibonisa ukuxolelwa okungaphelele (PR) ngosuku lwama-35 lokuhlolwa kwe-PET-CT, futhi zonke iziguli ezine-NR zatholakala zilahlekelwe yi-CD7 ngesikhathi sokulandelwa.

Isikhathi esimaphakathi sokubheka sasiyizinsuku ezingu-178 (izinsuku ezingu-28-izinsuku ezingu-776). Kulezi ziguli eziyisikhombisa ezithole i-CR, iziguli ezintathu ezaziphinde zabuyela emuva ngemva kokufakelwa i-substitution ngaphambilini zathola i-consolidation yesibili ye-allo-HSCT cishe ezinyangeni ezimbili ngemuva kokukhululwa yi-NS7CAR-T cell infusion, kanti isiguli esisodwa sahlala singenalo i-leukemia siphila ngosuku lwama-401, kanti iziguli ezimbili ezifakelwe i-substitution yesibili zafa ngezimbangela zokungaphindeli emuva ezinsukwini ezingama-241 kanye nezingu-776; ezinye iziguli ezine ezingazange zidlule kwi-consolidation yonke ye-HSCT, iziguli ezintathu zaphinde zabuyela emuva ezinsukwini ezingama-47, 83, kanye nezingu-89, ngokulandelana (ukulahlekelwa yi-CD7 kwatholakala kuzo zonke iziguli ezintathu), kanti isiguli esisodwa sashona ngenxa yokutheleleka kwamaphaphu.

Ngokuphepha, iningi leziguli (80%) lathola i-mild cytokine release syndrome (CRS) ngemva kokufakwa, kanti iziguli zebanga lesi-7 I, ibanga lesi-1 II, kanye neziguli ezimbili (20%) zathola i-CRS yebanga lesi-3. Azikho iziguli ezathola ubuthi be-neurological, kanti esinye sathola isifo se-mild cutaneous graft-versus-host.

Lo mphumela usikisela ukuthi i-NS7CAR-T ingaba yindlela ethembisayo yokufeza i-CR yokuqala esebenzayo ezigulini ezine-CD7-positive R/R AML, ngisho nangemva kokwelashwa ngezindlela eziningi kusenesikhathi. Futhi le ndlela iyiqiniso nasezigulini ezibhekana nokubuyela emuva ngemva kwe-allo-HSCT enephrofayili yokuphepha elawulekayo.

USolwazi Lu uthe, "Ngemininingwane esiyitholile kulokhu, ukwelashwa kwe-CD7 CAR-T kwe-R/R AML kusebenza kahle futhi kubekezelelwa kahle esigabeni sokuqala, futhi iningi leziguli likwazile ukuthola i-CR kanye nokukhululwa okujulile, okungelula. Futhi ezigulini ze-NR noma ezigulini eziphinde zabuyela ebudaleni, ukulahlekelwa yi-CD7 kuyinkinga enkulu. Ukuze kuhlolwe ngokugcwele ukusebenza kahle kwe-NS7CAR-T ekwelapheni i-CD7-positive AML, ukulandelwa ngokungangabazeki kusadinga ukuqinisekiswa ngokwengeziwe ngokuthola idatha eyengeziwe kubantu abaningi abagulayo kanye nesikhathi eside sokulandelwa, kodwa lokhu kunikeza ithemba elikhulu nokuzethemba emtholampilo."