Kutsegulidwa kwa ASH kwa 2023 | Dr. Peihua Lu Apereka CAR-T ya Kafukufuku wa Relapsed/Refractory AML

Kafukufuku wa gawo loyamba wa CD7 CAR-T wa R/R AML wochitidwa ndi gulu la Daopei Lu ku ASH

Msonkhano Wapachaka wa 65 wa American Society of Hematology (ASH) unachitika pa intaneti (San Diego, USA) komanso pa intaneti pa Disembala 9-12, 2023. Akatswiri athu adawonetsa bwino msonkhanowu, ndipo adapereka zotsatira zofufuza zoposa 60.

Zotsatira zaposachedwa za "Autologous CD7 CAR-T for relaxed/refractory acute myeloid leukemia (R/R AML)", zomwe zanenedwa pakamwa ndi Pulofesa Peihua Lu wa Chipatala cha Ludaopei ku China, zalandiridwa kwambiri.

Chithandizo cha R/R AML chimabweretsa vuto

R/R AML ili ndi vuto loipa, ngakhale ikapatsidwa chithandizo cha allogeneic hematopoietic hematopoietic stem cell transplantation (allo-HSCT), ndipo pakufunika chithandizo chamankhwala mwachangu. Malinga ndi Pulofesa Peihua Lu, kusankha njira yopezera chithandizo ndikofunikira kwambiri pakufunafuna njira zatsopano zochiritsira, ndipo pafupifupi 30% ya odwala a AML amawonetsa ma CD7 pa leukemoblasts awo ndi maselo oyambitsa matenda oopsa.

M'mbuyomu, Chipatala cha Lu Daopei chinanena za odwala 60 omwe adagwiritsa ntchito CD7 CAR-T (NS7CAR-T) yosankhidwa mwachilengedwe pochiza matenda a khansa ya m'magazi ndi ma lymphoma a T-cell, zomwe zikusonyeza kuti ndi yothandiza kwambiri komanso yotetezeka. Chitetezo ndi mphamvu ya kukula kwa NS7CAR-T kwa odwala omwe ali ndi CD7-positive R/R AML zidawonedwa ndikuwunikidwa mu kafukufuku wazachipatala wa Gawo I (NCT04938115) wosankhidwa pa Msonkhano Wapachaka wa ASH.

Pakati pa Juni 2021 ndi Januwale 2023, odwala 10 onse omwe anali ndi CD7-positive R/R AML (CD7 expression >50%) adalembetsa mu kafukufukuyu, ndi zaka zapakati pa zaka 34 (zaka 7 - zaka 63) Chiwerengero chapakati cha chotupa cha odwala omwe adalembetsa chinali 17%, ndipo wodwala m'modzi adapezeka ndi matenda a diffuse extramedullary disease (EMD). Nthawi yapakati kuyambira pa kudzipatula kwa maselo mpaka kulowetsedwa kwa maselo a CAR-T inali masiku 15, ndipo chithandizo chosinthira chinaloledwa kwa odwala omwe ali ndi matenda omwe akuipiraipira msanga asanaperekedwe. Odwala onse adalandira intravenous fludarabine (30 mg/m2/d) ndi cyclophosphamide (300 mg/m2/d) lymphatic removal chemotherapy kwa masiku atatu otsatizana.

Kutanthauzira kwa Ofufuza: Kuyamba kwa Kuchepetsa Kuzama

Asanalembetsedwe, odwala adapatsidwa chithandizo chapakati cha 8 (kuyambira: 3-17). Odwala 7 adapatsidwa chithandizo cha allogeneic hematopoietic stem cell transplantation (allo-HSCT), ndipo nthawi yapakati pakati pa kuikidwa ndi kubwereranso inali miyezi 12.5 (miyezi 3.5-19.5). Pambuyo pa kulowetsedwa, chiwerengero chapakati cha maselo a NS7CAR-T ozungulira chinali makope 2.72×105/μg (0.671~5.41×105 makope/μg) a genomic DNA, zomwe zidachitika pafupifupi tsiku la 21 (tsiku la 14 mpaka tsiku la 21) malinga ndi q-PCR, ndipo patsiku la 17 (tsiku la 11 mpaka tsiku la 21) malinga ndi FCM, yomwe inali 64.68% (40.08% mpaka 92.02%).

Chiwerengero chachikulu cha odwala omwe adalembetsa mu kafukufukuyu chinali pafupifupi 73%, ndipo panali ngakhale munthu m'modzi yemwe wodwalayo adalandira chithandizo 17 m'mbuyomu, anatero Pulofesa Peihua Lu. Odwala awiri omwe adachitidwa opaleshoni ya allo-HSCT adabwereranso mkati mwa miyezi isanu ndi umodzi atapatsidwa opaleshoni. N'zoonekeratu kuti chithandizo cha odwalawa chili ndi "zovuta ndi zopinga".

Deta yolonjeza

Masabata anayi pambuyo poika maselo a NS7CAR-T, asanu ndi awiri (70%) adapeza chikhululukiro chonse (CR) mu fupa la mafupa, ndipo asanu ndi mmodzi adapeza CR negative chifukwa cha matenda otsalira a microscopic (MRD). Odwala atatu sanapeze chikhululukiro (NR), ndipo wodwala m'modzi yemwe ali ndi EMD adawonetsa chikhululukiro chochepa (PR) pa tsiku la 35 la PET-CT, ndipo odwala onse omwe ali ndi NR adapezeka kuti ali ndi kutayika kwa CD7 panthawi yotsatiridwa.

Nthawi yowunikira yapakati inali masiku 178 (masiku 28 mpaka masiku 776). Mwa odwala asanu ndi awiri omwe adapeza CR, odwala atatu omwe adabwereranso pambuyo popatsidwa chithandizo cham'mbuyomu adapatsidwa chithandizo chachiwiri cha allo-HSCT pafupifupi miyezi iwiri kuchokera pamene adapatsidwa chithandizo cha NS7CAR-T, ndipo wodwala m'modzi adakhalabe wopanda leukemia wamoyo pa tsiku la 401, pomwe odwala awiri omwe adalandira chithandizo chachiwiri adamwalira chifukwa cha zifukwa zosabwereranso pa masiku 241 ndi 776; odwala ena anayi omwe sanalandire chithandizo chachiwiri cha allo-HSCT, odwala atatu adabwereranso pa masiku 47, 83, ndi 89, motsatana (kutayika kwa CD7 kunapezeka mwa odwala onse atatu), ndipo wodwala m'modzi adamwalira ndi matenda a m'mapapo.

Ponena za chitetezo, odwala ambiri (80%) adakumana ndi mild cytokine release syndrome (CRS) atapatsidwa jekeseni, ndipo odwala a giredi 7 I, giredi 1 II, ndi odwala awiri (20%) adakumana ndi giredi III CRS. Palibe odwala omwe adakumana ndi vuto la neurotoxicity, ndipo m'modzi adadwala matenda amitsempha ya khungu omwe adalumikizidwa ndi graft-versus-host.

Zotsatirazi zikusonyeza kuti NS7CAR-T ikhoza kukhala njira yabwino yopezera CR yothandiza kwa odwala omwe ali ndi CD7-positive R/R AML, ngakhale atalandira chithandizo chambiri nthawi yomweyo. Ndipo njira imeneyi ndi yowonanso kwa odwala omwe amabwereranso kuchipatala atatha kugwiritsa ntchito mankhwala a allo-HSCT omwe ali ndi chitetezo chokwanira.

Pulofesa Lu anati, "Kudzera mu deta yomwe tapeza nthawi ino, chithandizo cha CD7 CAR-T cha R/R AML ndi chothandiza kwambiri ndipo chimaloledwa bwino pachiyambi, ndipo odwala ambiri adatha kupeza CR ndi kuchira kwakukulu, zomwe sizophweka. Ndipo mwa odwala a NR kapena odwala omwe abwereranso kuchipatala, kutayika kwa CD7 ndiye vuto lalikulu. Kuti tiwone bwino momwe NS7CAR-T imagwirira ntchito pochiza AML yokhala ndi CD7, kutsatira mosakayikira kuyenera kutsimikiziridwa kwambiri mwa kupeza deta yambiri kuchokera kwa odwala ambiri komanso nthawi yayitali yotsata, koma izi zimapatsanso chiyembekezo ndi chidaliro chachikulu ku chipatala."