Pulofesa wa ku yunivesite ya ku Russia wazaka za m'ma 70 ali ndi matenda a multiple myeloma. Atalandira chithandizo chamankhwala ambiri komanso kubwereranso kawiri kwa opaleshoni ya autologous, adaphunzira za chithandizo chamakono chothana ndi khansa cha CAR-T ku China, kotero adabwera ku China kudzalandira chithandizo cha maselo a CAR-T ndipo adatulutsidwa bwino atatha masiku 13 akubwezeretsanso. Ndipo m'mbiri yaposachedwa, dokotalayo wawona kale mkhalidwe wa relieve (CR) mu zotsatira zake zowunika.
Chithandizo cha CAR-T, kapena chithandizo cha chimeric antigen receptor T-cell, ndi chitukuko chachikulu pa chithandizo cha maselo opangidwa ndi munthu payekha cha khansa. Njirayi imaphatikizapo kusonkhanitsa maselo a T a wodwalayo, kenako kusintha kwa majini a T-cells mu vitro kumapangidwa kuti kuwonjezere mphamvu ya maselo a T kuzindikira khansa. Maselo a T osinthidwawa (monga maselo a CAR-T) amabwezeretsedwa kwa wodwalayo.
KQ-2003 ndi mankhwala a BCMA/CD19 a CAR T-cell omwe amagwiritsa ntchito njira ziwiri, pogwiritsa ntchito kapangidwe katsopano ka CAR kofanana kuti awonjezere ntchito ya maselo ndi kupirira kwawo, ndipo kapangidwe ka CAR kawiri kamachepetsa kupewa kwa antigen kwa chithandizo chimodzi.
Kafukufuku woyambitsidwa ndi Ofufuza (NCT04714827) ku China cholinga chake ndi kuwunika chitetezo, kulekerera, komanso kugwira ntchito bwino kwa maselo a KQ-2003 CAR-T mwa odwala (pts) omwe ali ndi myeloma yambiri yobwereranso/yosasinthika (RRMM), makamaka kwa iwo omwe ali ndi matenda a extramedullary (EMD).
Njira
Kuyesa kumeneku, komwe kumakhala ndi malo ambiri, kotseguka, komanso kuchuluka kwa mlingo kumalembetsa ma RRMM pts okhala ndi njira ≥1 zamankhwala am'mbuyomu kuphatikiza proteasome inhibitor (PI), ndi mankhwala oletsa immunomodulatory (IMiDs), ndi/kapena anti-CD38. Ma Pts adalandira lymphodepletion ndi fludarabine (30 mg/m2/tsiku) ndi cyclophosphamide (300 mg/m2/tsiku) pa masiku -5 mpaka -3, kenako kulowetsedwa kamodzi m'mitsempha kwa maselo a KQ-2003 CAR-T (tsiku 0) m'magawo atatu a mlingo (DL) kutengera kapangidwe ka 3+3: DL1, DL2, kapena DL3 (maselo 1.0, 2.0, kapena 3.0×106 CAR+/kg). Cholinga chinali kuwunika chitetezo, kulekerera, mphamvu yoyambirira ndi makhalidwe a PK/PD, ndikudziwa mlingo waukulu wolekerera (MTD), poizoni woletsa mlingo (DLT). Yankho la magazi linayesedwa motsatira miyezo ya IMWG ndi matenda otsalira ochepa (MRD) ndi kayendedwe katsopano ka mbadwo (NGF). EMD inayesedwa motsatira Ndondomeko Yoyankhira ya Kukonzanso kwa PET.
Zotsatira
Pofika kumapeto kwa chithandizo chamankhwala cha Jul.25, 2024, mapointi 23 (52.2% amuna; apakati azaka 64 (apakati 52-77)) omwe ali ndi RRMM adalandira KQ-2003 (3 DL1, 11 DL2 ndi 9 DL3). Nthawi yotsatila yapakati inali miyezi 13.7 (apakati 2.1-35.2). Mapointi adalandira apakati a mizere 5 ya chithandizo cham'mbuyomu (apakati 2-11). 91.3% (21/23) anali ndi refractory katatu, ndipo 26.1% (6/23) penta-refractory. 65.2% (15/23) anali ndi cytogenetic profile yoopsa kwambiri/yoopsa kwambiri.
60.9% (14/23) ya ma pts anali ndi EMD poyambira, kuphatikizapo ma extramedullary extraosseous 7 (EM-E), 5 extramedullary-bone related (EM-B), 2 pts ndi zonse ziwiri.
Mu gulu la EMD, ma pts 5 (5/14, 35.7%) alibe zizindikiro zoyezera magazi, ndipo yankho linayesedwa ndi PET-CT.
Chiŵerengero cha mayankho onse a magazi (ORR) chinali 100.0% (18/18), ndi chiŵerengero cha sCR/CR cha 88.9% (16/18), chiŵerengero cha VGPR cha 11.1% (2/18). Nthawi yapakati mpaka yankho loyamba inali 1.2 mwezi (N=18, mulingo 0.6–3.1; 22.2% ≤1.0 mwezi), ndipo nthawi yapakati mpaka CR/sCR inali 2.7 mwezi (N=16, mulingo 0.6–9.1; 50.0% ≤3.0 mwezi). Pa ma pts 19 omwe amayesedwa ndi MRD, 100% anali opanda MRD (10-5), ndipo chiŵerengero cha MRD-neg cha miyezi 6 ndi 12 chinali 80.0% (8/10) ndi 100.0% (3/3), motsatana.
PET ORR ya ma EMD pts inali 85.7% (12/14), kuphatikizapo 64.3% (9/14) yankho lonse la kagayidwe kachakudya (CMR), 21.4% (3/14) yankho la kagayidwe kachakudya (PMR) ndi 14.3% (2/14) matenda okhazikika a kagayidwe kachakudya (SMD). 64.3% (9/14) ndi 50.0% (7/14) a ma EMD pts anali ndi > 50% ndi > 75% kuchepa kwa kukula kwa plasmacytomas ya minofu yofewa, motsatana. Mu ma EMD pts 5 opanda zizindikiro zoyezera zamagazi, PET ORR inali 80% (4/5) (2 CMR, 2 PMR ndi 1 SMD).
Nthawi yapakati yoyankhira (DOR) sinafike (NR). Chiwerengero cha miyezi 6 chopulumuka popanda kupita patsogolo (PFS) ndi chiwerengero cha moyo wonse (OS) chinali 86.5% (73.4–100) ndi 86.2% (72.8–100), chiwerengero cha miyezi 12 cha PFS ndi OS chinali 75.3% (58.4–97.0) ndi 86.2% (72.8–100) motsatana. Chiwerengero chapakati cha PFS ndi OS chinali NR.
Anthu anayi onse anamwalira, kuphatikizapo awiri omwe adapezeka pa kafukufuku ndipo adayesedwa kuti ndi okhudzana ndi chithandizo (onse awiri omwe ali ndi chibayo chachikulu), ndi awiri omwe adamwalira chifukwa cha PD.
CRS ndi ICANS motsatana zinawonedwa mu 21/23 (91.3%, giredi 3/4 4.3%), ndi 5/23 (21.7%, giredi 3/4 8.7%). Nthawi yapakati yoyambira CRS inali 5d (range 1-9) ndi nthawi yapakati ya 4d (range 1-15). Nthawi yapakati yoyambira ICANS inali 10d (range 8-23) ndi nthawi yapakati ya 3d (range 1-9). Palibe DLTs zomwe zinawonedwa.
Nambala ya makopi a maselo a KQ-2003 CAR+ T (VCN) inasonyeza kuti Tmax yapakati inali 14.0, 11.5, ndi 9.0 tsiku mu DL1, DL2 ndi DL3, motsatana. Cmax yapakati inali makope 140.6, 168.2, ndi 83.9 pa DNA imodzi yokhala ndi nthawi yayitali. Pakati pa mavoti omwe anali ndi miyezi 6 ndi 12 yotsatira, 66.7% (10/15) ndi 62.5% (5/8) anali ndi maselo a CAR+ T omwe amaoneka m'magazi ozungulira.
Mapeto
BCMA/CD19 yolimbana ndi zinthu ziwiri ya CAR-T KQ-2003 yawonetsa kuyankha koyambirira, kozama komanso kolimba mu RRMM yokhala ndi chitetezo chovomerezeka. Chofunika kwambiri, inali ndi mphamvu yodalirika mu EMD pts, kuphatikizapo EM-E yodwala, yomwe ikufunika kufufuzidwa kwina.
Pakadali pano, pali mayeso ena ambiri azachipatala a CAR-T ku China, ndipo akufunafuna odwala. Kuti mumve zambiri za mankhwala ndi ukadaulo watsopano, mutha kulumikizana ndi Dipatimenti Yapadziko Lonse ya Chipatala cha Oncology ku Beijing South Region.
Nambala ya Foni: 4008803716
Imelo：myimmnet@163.com
Zolemba
1.http://en.novatim-zj.com/show-28-32-1.html
2.https://ash.confex.com/ash/2024/webprogram/Paper201160.html
3.http://myimm.net/mianyizhiliao/1939.html
Nthawi yotumizira: Novembala-26-2024