Kuvhurwa kweASH kwa2023 | Dr. Peihua Lu Anopa CAR-T yeRelapsed/Refractory AML Research

Chidzidzo chekiriniki chechikamu chekutanga cheCD7 CAR-T yeR/R AML chakaitwa nechikwata chaDaopei Lu paASH

Musangano wegore negore wechi65 weAmerican Society of Hematology (ASH) wakaitwa pasina internet (San Diego, USA) uye online musi wa9-12 Zvita, 2023. Nyanzvi dzedu dzakaratidza zvakanaka musangano uyu, dzichipa mhinduro dzekutsvaga dzinopfuura makumi matanhatu.

Mhedzisiro yazvino ye "Autologous CD7 CAR-T yerecovery/refractory acute myeloid leukemia (R/R AML)", yakataurwa nemuromo naProf. Peihua Lu vekuLudaopei Hospital muChina, yakagamuchirwa zvakanyanya.

Kurapwa kweR/R AML kune dambudziko

R/R AML haina fungidziro yakanaka, kunyangwe painenge ichiiswa allogeneic hematopoietic hematopoietic stem cell transplantation (allo-HSCT), uye pane chikonzero chekukurumidzira chekurapa nzira itsva dzekurapa. Sekureva kwaProf. Peihua Lu, kusarudza chinangwa kwakakosha mukutsvaga mishonga mitsva, uye vanenge 30% yevarwere veAML vanoratidza CD7 pamaleukemoblasts avo nemasero emhuka anouraya.

Kare, Chipatara cheLu Daopei chakashuma varwere makumi matanhatu vakashandisa CD7 CAR-T (NS7CAR-T) yakasarudzwa nenzira yechisikigo pakurapa T-cell acute leukemias uye lymphomas, zvichiratidza kushanda kwakakosha uye kuchengetedzeka kwakanaka. Kuchengetedzeka uye kushanda kwekuwedzera kweNS7CAR-T muvarwere vane CD7-positive R/R AML kwakaonekwa uye kwakaongororwa muchidzidzo chekiriniki chePhase I (NCT04938115) chakasarudzwa paMusangano weGore weASH uyu.

Pakati paChikumi 2021 naNdira 2023, varwere gumi vane CD7-positive R/R AML (CD7 expression >50%) vakanyoreswa muchidzidzo ichi, vaine makore akaenzana nemakore makumi matatu nemana (makore manomwe - makore makumi matanhatu nematatu) Avhareji yehuwandu hwegomarara revarwere vakanyoreswa yaive 17%, uye murwere mumwe chete aive nechirwere che diffuse extramedullary disease (EMD). Nguva yepakati kubva pakupatsanurwa kwemasero kusvika pakuiswa kweCAR-T cell yaive mazuva gumi nemashanu, uye kurapa kwekuchinja kwakabvumidzwa kune varwere vane chirwere chiri kuramba chichiipa vasati vapihwa mushonga. Varwere vese vakapihwa intravenous fludarabine (30 mg/m2/d) uye cyclophosphamide (300 mg/m2/d) lymphatic removal chemotherapy kwemazuva matatu akatevedzana.

Dudziro yeMuongorori: Kutanga kweKuderedza Zvakadzika

Vasati vanyoreswa, varwere vakanyoreswa nzira yekurapa ye frontline avhareji ye8 (kubva pa: 3-17). Varwere vanomwe vakange vamboiswa allogeneic hematopoietic stem cell transplantation (allo-HSCT), uye nguva yepakati pakati pekuisirwa uye kudzokera shure yaive mwedzi 12.5 (mwedzi 3.5-19.5). Mushure mekuisirwa, avhareji yepamusoro yemasero eNS7CAR-T aitenderera yaive 2.72×105 copies/μg (0.671~5.41×105 copies/μg) ye genomic DNA, iyo yakaitika pazuva rinenge re21 (zuva re14 kusvika zuva re21) zvichienderana ne q-PCR, uye pazuva re17 (zuva re11 kusvika zuva re21) zvichienderana ne FCM, iyo yaive 64.68% (40.08% kusvika 92.02%).

Purofesa Peihua Lu vakati bundu rakanyanya kuwanda muvarwere vakanyoreswa muchidzidzo ichi raive pedyo ne73%, uye paive nechiitiko chimwe chete apo murwere akamborapwa ka17 kare. Vaviri vevarwere vakamborapwa neHSCT vakadzoka mukati memwedzi mitanhatu mushure mekuisirwa bundu. Zviri pachena kuti kurapwa kwevarwere ava kwakazara ne "matambudziko nezvipingamupinyi".

Ruzivo runovimbisa

Mavhiki mana mushure mekuiswa kwemasero eNS7CAR-T, vanomwe (70%) vakawana relieve yakakwana (CR) mumongo wemapfupa, uye vatanhatu vakawana CR negative nekuda kwe microscopic residual disease (MRD). Varwere vatatu havana kuwana relieve (NR), murwere mumwe chete ane EMD akaratidza partial relieve (PR) pazuva rechi35 rekuongorora PET-CT, uye varwere vese vane NR vakawanikwa vaine CD7 kurasikirwa panguva yekutevera.

Nguva yepakati yekutarisa yaive mazuva 178 (mazuva 28-mazuva 776). Pavarwere vanomwe vakawana CR, varwere vatatu vakadzokera kuchipatara mushure mekuisirwa mushonga wechipiri vakazobatanidzwa ne NS7CAR-T cell consolidation second allo-HSCT mwedzi miviri mushure mekurerutsirwa mushonga weNS7CAR-T cell, uye murwere mumwe chete akaramba asina leukemia ari mupenyu pazuva rechi401, nepo varwere vaviri vakaisirwa mushonga wechipiri vakafa nezvikonzero zvisina kudzokera kuchipatara pazuva rechi241 nerechi776; vamwe varwere vana vasina kupinda mu HSCT consolidation, varwere vatatu vakadzokera kuchipatara pazuva rechi47, rechi83, nerechi89, zvichiteerana (kurasikirwa neCD7 kwakawanikwa muvarwere vese vatatu), uye murwere mumwe chete akafa nehutachiona hwemapapu.

Panyaya yekuchengetedzeka, ruzhinji rwevarwere (80%) vakasangana nechirwere chemild cytokine release syndrome (CRS) mushure mekuisirwa mushonga, varwere vegiredhi 7 I, giredhi 1 II, uye varwere vaviri (20%) vakasangana neCRS yegiredhi III. Hapana varwere vakasangana nechirwere chepfungwa, uye mumwe chete akava nechirwere chemild cutaneous graft-versus-host.

Izvi zvinoratidza kuti NS7CAR-T inogona kunge iri nzira yakanaka yekuwana CR yekutanga inoshanda kune varwere vane CD7-positive R/R AML, kunyangwe mushure mekurapwa kakawanda pakutanga. Uye iyi nzira inoshandawo kune varwere vanodzokera shure mushure me allo-HSCT vane ruzivo rwakachengeteka.

Prof. Lu vakati, "Kuburikidza nedata ratakawana panguva ino, kurapwa kweCD7 CAR-T kweR/R AML kunoshanda uye kunobvumirwa zvakanaka pakutanga, uye ruzhinji rwevarwere vakakwanisa kuwana CR uye kurerukirwa kwakadzika, izvo zvisiri nyore. Uye muvarwere veNR kana varwere vakadzokera shure, kurasikirwa neCD7 ndiro dambudziko guru. Kuti tiongorore zvizere kushanda kweNS7CAR-T mukurapa CD7-positive AML, kutevera pasina mubvunzo kunofanira kusimbiswa zvakanyanya nekuwana data rakawanda kubva kuvarwere vakawanda uye nguva yakareba yekutevera, asi izvi zvinopawo tariro yakawanda nechivimbo kukiriniki."