2023 ASH Ukuvulwa | UDkt. Peihua Lu Wethula I-CAR-T Yocwaningo Lwe-AML Olubuyelelwe kabusha /Refractory

Ucwaningo lomtholampilo lwesigaba I se-CD7 CAR-T se-R/R AML olwenziwa yiqembu lika-Daopei Lu luqala ngo-ASH

Umhlangano Waminyaka Yonke Wama-65 we-American Society of Hematology (ASH) wabanjwa ungaxhunyiwe ku-inthanethi (e-San Diego, e-USA) futhi ku-inthanethi ngo-December 9-12, 2023.Izazi zethu zenze umbukiso omuhle wale ngqungquthela, zanikela ngemiphumela yocwaningo engaphezu kuka-60.

Imiphumela yakamuva ye-"Autologous CD7 CAR-T for relapsed/refractory acute myeloid leukemia (R/R AML)", ebikwe ngomlomo uProf. Peihua Lu weSibhedlela saseLudaopei eChina, inakwe kakhulu.

Ukwelashwa kwe-R/R AML kuveza inkinga

I-R/R AML ine-prognosis embi, ngisho nalapho i-allogeneic hematopoietic stem cell transplantation (i-allo-HSCT), futhi kunesidingo esiphuthumayo somtholampilo sezinketho zokwelapha ezinoveli.NgokukaProf. Peihua Lu, ukukhethwa okuhlosiwe kubalulekile ekufuneni izindlela zokwelapha ezintsha, futhi cishe u-30% weziguli ze-AML ziveza i-CD7 kuma-leukemoblasts azo kanye namaseli abulalayo abangela ukuzalwa.

Ngaphambilini, isibhedlela iLu Daopei sabika iziguli ezingu-60 ezifake isicelo se-CD7 CAR-T (NS7CAR-T) ezikhethiwe ngokwemvelo zokwelashwa kwe-T-cell acute leukemias kanye ne-lymphomas, okubonisa ukusebenza kahle okuphawulekayo kanye nephrofayili yokuphepha evumayo.Ukuphepha nokusebenza kwe-NS7CAR-T ukunwetshwa kweziguli ezine-CD7-positive R/R AML kwabonwa futhi kwahlolwa ocwaningweni lomtholampilo lweSigaba I (NCT04938115) olukhethelwe lo Mhlangano Waminyaka Yonke we-ASH.

Phakathi kukaJuni 2021 noJanuwari 2023, isibalo seziguli eziyi-10 ezine-CD7-positive R/R AML (inkulumo ye-CD7> 50%) zabhaliswa ocwaningweni, zineminyaka yobudala engama-34 (iminyaka eyi-7 - iminyaka engama-63)Isimila esimaphakathi. Umthwalo weziguli ezibhalisiwe wawungu-17%, kanti isiguli esisodwa sanikezwa isifo esibizwa ngokuthi i-diffuse extramedullary disease (EMD) . ukumnika kwalawulwa.Zonke iziguli zithole i-fludarabine emithanjeni (30 mg/m2/d) kanye ne-cyclophosphamide (300 mg/m2/d) i-lymphatic remove chemotherapy izinsuku ezintathu ezilandelanayo.

Ukuhunyushwa Komcwaningi: I-Dawn of Deep Mitigation

Ngaphambi kokubhaliswa, iziguli zithole i-median ye-8 (ububanzi: 3-17) yokwelapha engaphambili. Iziguli ezingu-7 zazithole i-allogeneic hematopoietic stem cell transplantation (i-allo-HSCT), futhi isikhathi esimaphakathi phakathi kokufakelwa kanye nokubuyela emuva kwakuyizinyanga ezingu-12.5 (izinyanga ezingu-3.5-19.5) . amakhophi/μg (0.671~5.41×105 amakhophi/μg) e-DNA ye-genomic, eyenzeka cishe ngosuku lwama-21 (usuku lwe-14 kuya osukwini lwama-21) ngokusho kwe-q-PCR, futhi ngosuku lwe-17 (usuku lwe-11 kuya osukwini lwama-21) ngokusho kwe-FCM , okwakungu-64.68% ( 40.08% kuya ku-92.02%).

Umthwalo we-tumor ophakeme kakhulu weziguli ezibhalise ocwaningweni wawusondele ku-73%, futhi kwakukhona ngisho necala elilodwa lapho isiguli sasithole ukwelashwa kwangaphambilini kwe-17, kusho uProf. Peihua Lu. Okungenani ezimbili zeziguli ezathola i-allo-HSCT zaphinde zaphindeka phakathi nezinyanga eziyisithupha zokufakelwa kabusha. Kuyacaca ukuthi ukwelashwa kwalezi ziguli kugcwele "ubunzima nezithiyo".

Idatha ethembisayo

Emasontweni amane ngemuva kokujova iseli le-NS7CAR-T, abayisikhombisa (70%) bathole ukuxolelwa okuphelele (CR) emnkantsheni, kwathi abayisithupha bathola i-CR negative ye-microscopic residual disease (MRD). iziguli ezintathu azizange zizuze ukukhululwa (NR), nesiguli esisodwa esine-EMD esibonisa ukukhululwa okuyingxenye (PR) ngosuku lwe-35 ukuhlolwa kwe-PET-CT, futhi zonke iziguli ezine-NR zatholakala ukuthi zine-CD7 yokulahlekelwa ekulandeleni.

Isikhathi sokubuka esimaphakathi kwakuyizinsuku eziyi-178 (izinsuku ezingama-28-izinsuku ezingama-776). Ezigulini eziyisikhombisa ezithole i-CR, iziguli ezintathu ezaziphinde zabuyela emuva ngemva kokufakelwa kabusha zathola ukuhlanganiswa kwe-allo-HSCT yesibili cishe izinyanga ezi-2 ngemva kokukhululwa ngokufakwa kweseli ye-NS7CAR-T, futhi isiguli esisodwa sahlala singenayo i-leukemia siphila ngosuku lwama-401, kuyilapho ezimbili zesibili- iziguli zokufakelwa zafa ngenxa yezizathu zokungabuyeli ezinsukwini ezingama-241 no-776; ezinye iziguli ezine ezingazange zithole ukuhlanganiswa kwe-HSCT, iziguli ezi-3 zaphindela emuva ezinsukwini ezingama-47, 83, nezingama-89, ngokulandelana (ukulahleka kwe-CD7 kutholakale kuzo zontathu iziguli), kanti isiguli esisodwa sashona ngenxa yesifo samaphaphu.

Mayelana nokuphepha, iningi leziguli (80%) labhekana ne-mild cytokine release syndrome (CRS) ngemva kokujova, ne-7 grade I, 1 grade II, kanye neziguli ze-2 (20%) zathola i-CRS ye-grade III. azikho iziguli ezaba ne-neurotoxicity, futhi esi-1 saba nesifo esithambile se-graft-versus-host.

Lo mphumela uphakamisa ukuthi i-NS7CAR-T ingaba uhlobo oluthembisayo lokuthola i-CR yokuqala esebenzayo ezigulini ezine-CD7-positive R/R AML, ngisho nangemva kokuthola imigqa eminingi yokwelashwa ngaphambili. Futhi lolu hlobo lwemithi luyiqiniso ezigulini ezibuyelwa wumqemane ngemva kwe-allo-HSCT enephrofayili yokuphepha elawulekayo.

UProfesa Lu uthe, "Ngolwazi esilutholile ngalesi sikhathi, ukwelashwa kwe-CD7 CAR-T ye-R/R AML kusebenza kahle futhi kubekezelelwa kahle ekuqaleni, futhi iningi leziguli likwazile ukuthola i-CR kanye nokukhululwa okujulile. , okungekho lula Futhi ezigulini ze-NR noma iziguli eziphinde zagula, ukulahlekelwa kwe-CD7 kuyinkinga enkulu Ukuze kuhlolwe ngokugcwele ukusebenza kwe-NS7CAR-T ekwelapheni i-CD7-positive AML, ukulandelela ngokungangabazeki kusadinga ukuqinisekiswa okwengeziwe. ngokuthola idatha eyengeziwe kubantu abaningi beziguli kanye nesikhathi eside sokulandelela, kodwa lokhu kunikeza ithemba elikhulu nokuzethemba emtholampilo."