2023 ASH Kutsegula | Dr. Peihua Lu Akupereka CAR-T kwa Kafukufuku Wobwereranso /Refractory AML

Phunziro lachipatala la gawo loyamba la CD7 CAR-T la R/R AML lolembedwa ndi gulu la Daopei Lu lidayamba pa ASH.

Msonkhano Wapachaka wa 65 wa American Society of Hematology (ASH) unachitika popanda intaneti (San Diego, USA) komanso pa intaneti pa December 9-12, 2023.Akatswiri athu adawonetsa bwino kwambiri msonkhano uno, ndikupereka zotsatira zoposa 60 zafukufuku.

Zotsatira zaposachedwa za "Autologous CD7 CAR-T for relapsed/refractory acute myeloid leukemia (R/R AML)", zomwe zinanenedwa ndi Prof. Peihua Lu wa kuchipatala cha Ludaopei ku China, adalandira chidwi kwambiri.

Chithandizo cha R/R AML chimapereka vuto

R/R AML ili ndi vuto losazindikira bwino, ngakhale ikadutsa allogeneic hematopoietic stem cell transplantation (allo-HSCT), ndipo pakufunika kufunikira kwachipatala kwa njira zatsopano zochizira. Malinga ndi Prof. Peihua Lu, kusankha chandamale ndikofunikira pakufufuza mankhwala atsopano, ndipo pafupifupi 30% ya odwala AML amasonyeza CD7 pa leukemoblasts awo ndi maselo oipa obadwa nawo.

M'mbuyomu, Chipatala cha Lu Daopei chinanena odwala 60 omwe adagwiritsa ntchito CD7 CAR-T (NS7CAR-T) yosankhidwa mwachilengedwe pochiza T-cell pachimake khansa ya m'magazi ndi ma lymphomas, kuwonetsa kuchita bwino komanso mbiri yabwino yachitetezo. kuwonjezeka kwa odwala omwe ali ndi CD7-positive R/R AML kunawonedwa ndikuwunikidwa mu phunziro lachipatala la Phase I (NCT04938115) losankhidwa pa Msonkhano Wapachaka wa ASH.

Pakati pa Juni 2021 ndi Januware 2023, odwala 10 omwe ali ndi CD7-positive R/R AML (CD7 mawu> 50%) adalembetsa nawo kafukufukuyu, omwe ali ndi zaka zapakati pazaka 34 (zaka 7 - 63) kuchuluka kwa odwala omwe adalembetsa anali 17%, ndipo wodwala m'modzi yemwe anali ndi matenda a extramedullary (EMD). Odwala onse analandira mtsempha wa fludarabine (30 mg/m2/d) ndi cyclophosphamide (300 mg/m2/d) lymphatic kuchotsa chemotherapy kwa masiku atatu otsatizana.

Kutanthauzira Kwakafukufuku: Dawn of Deep Mitigation

Asanalembetse, odwala adalandira chithandizo chapakati cha 8 (range: 3-17) kutsogolo. Odwala 7 anali atadutsa allogeneic hematopoietic stem cell transplantation (allo-HSCT), ndipo nthawi yapakati pakati pa kuikidwa ndi kubwereranso inali miyezi 12.5 (miyezi 3.5-19.5). makope/μg (0.671 ~ 5.41 × 105 makope/μg) a genomic DNA, zomwe zinachitika pafupifupi tsiku 21 (tsiku 14 mpaka tsiku 21) molingana ndi q-PCR, ndi tsiku 17 (tsiku 11 mpaka tsiku 21) malinga ndi FCM , yomwe inali 64.68% (40.08% mpaka 92.02%).

Chotupa chachikulu kwambiri cha odwala omwe adalembetsa nawo phunziroli chinali pafupi ndi 73%, ndipo panalinso vuto limodzi pomwe wodwalayo adalandira chithandizo cham'mbuyomu 17, adatero Prof. Peihua Lu. Osachepera awiri mwa odwala omwe adadwala allo-HSCT adakumananso ndi miyezi isanu ndi umodzi atamuika. Zikuwonekeratu kuti chithandizo cha odwalawa chili ndi "zovuta ndi zopinga".

Deta yolonjeza

Patatha milungu inayi NS7CAR-T cell infusion, asanu ndi awiri (70%) adapeza chikhululukiro chonse (CR) m'mafupa, ndipo asanu ndi limodzi adapeza CR negative ya microscopic residual disease (MRD). odwala atatu sanapeze chikhululukiro (NR), ndi wodwala m'modzi yemwe ali ndi EMD akuwonetsa kukhululukidwa pang'ono (PR) pa tsiku la 35 PET-CT kuunikira, ndipo odwala onse omwe ali ndi NR adapezeka kuti ali ndi CD7 kutaya pakutsatira.

Nthawi yowonera apakatikati inali masiku 178 (masiku 28-masiku 776). Mwa odwala asanu ndi awiri omwe adapeza CR, odwala atatu omwe adabwerera m'mbuyo atawaika m'mbuyomu adalumikizidwa kachiwiri allo-HSCT pafupifupi miyezi iwiri atakhululukidwa ndi kulowetsedwa kwa cell NS7CAR-T, ndipo wodwala m'modzi adakhalabe wopanda khansa ya m'magazi pa tsiku la 401, pomwe awiri sekondi- Odwala omwe adamuika adamwalira chifukwa chosabwereranso m'masiku 241 ndi 776; odwala ena anayi omwe sanapatsidwe gawo lophatikizana- HSCT, odwala 3 adayambiranso masiku 47, 83, ndi 89, motsatana (kutayika kwa CD7 kunapezeka mwa odwala onse atatu), ndipo wodwala m'modzi adamwalira ndi matenda am'mapapo.

Pankhani ya chitetezo, odwala ambiri (80%) adakumana ndi matenda otsika a cytokine release (CRS) atatha kulowetsedwa, ndi 7 grade I, 1 grade II, ndi 2 odwala (20%) adakumana ndi grade III CRS. palibe odwala omwe adakumana ndi vuto la neurotoxicity, ndipo m'modzi adadwala matenda ophatikizika amtundu wocheperako.

Zotsatirazi zikuwonetsa kuti NS7CAR-T ikhoza kukhala njira yodalirika yopezera CR yabwino kwa odwala omwe ali ndi CD7-positive R/R AML, ngakhale atalandira chithandizo chambiri chamtsogolo. Ndipo regimen iyi ndi yowonanso kwa odwala omwe amayambiranso pambuyo pa allo-HSCT omwe ali ndi mbiri yotetezeka yotetezeka.

Pulofesa Lu adati, "Kudzera mu deta yomwe tapeza nthawi ino, chithandizo cha CD7 CAR-T cha R / R AML ndi chothandiza kwambiri komanso cholekerera kumayambiriro, ndipo odwala ambiri adatha kukwaniritsa CR ndi kukhululukidwa kwakukulu. , zomwe sizili zophweka Ndipo kwa odwala a NR kapena odwala omwe abwereranso, kutaya kwa CD7 ndilo vuto lalikulu Kuti muwone bwino momwe NS7CAR-T imathandizira pochiza CD7-positive AML, mosakayikira kutsatiridwa kumafunikabe kutsimikiziridwa. mwa kupeza zambiri kuchokera kwa odwala ochulukirapo komanso nthawi yayitali yotsatila, koma izi zimaperekanso chiyembekezo komanso chidaliro ku chipatala. "