Unjingalwazi weyunivesithi yaseRashiya okwiminyaka yakhe yokugqibela engamashumi asixhenxe unesifo esiphambili se-multiple myeloma. Emva kokufumana unyango oluninzi kunye nokuphinda kabini utyando lwe-autologous, wafunda ngonyango oluphambili lokulwa nomhlaza i-CAR-T eTshayina, ngoko weza eTshayina ukuze afumane unyango lweeseli ze-CAR-T waza wakhululwa kakuhle emva kweentsuku ezili-13 zokufakelwa kwakhona. Kwaye kwingxelo yamva nje yokulandelela, ugqirha sele ebone imeko epheleleyo yokukhululwa (CR) kwiziphumo zakhe zovavanyo.
Unyango lwe-CAR-T, okanye unyango lwe-chimeric antigen receptor T-cell, luphumelelo olukhulu kwi-immunotherapy yeeseli ezenzelwe wena umhlaza. Le nkqubo ibandakanya ukuqokelelwa kwee-T-cells zesigulane, emva koko kwenziwa utshintsho lwe-in vitro genetic engineering yee-T-cells ukuphucula amandla ee-T-cells okubona ngokukodwa umhlaza. Ezi T-cells ziguquliweyo (oko kukuthi, ii-CAR-T cells) emva koko zibuyiselwa kwisigulana.
I-KQ-2003 yimveliso yonyango lwe-CAR T-cell ye-BCMA/CD19 ejolise kwiiseli ezimbini, isebenzisa ulwakhiwo lwamva nje lwe-CAR oluhambelanayo ukuphucula umsebenzi weseli kunye nokuqina, kunye nolwakhiwo lwe-CAR ezimbini lunciphisa ukuphepha i-antigen yonyango olujoliswe kwi-single target.
Uphononongo oluqalisiweyo loPhando (NCT04714827) eTshayina lujolise ekuvavanyeni ukhuseleko, ukunyamezeleka, kunye nokusebenza kakuhle kweeseli ze-KQ-2003 CAR-T kwizigulane (pts) ezine-relapse/refractory multiple myeloma (RRMM), ingakumbi kwabo banesifo esingaphandle kwe-medullary disease (EMD).
Indlela
Olu vavanyo lokunyuka kwedosi oluneziko ezininzi, oluvulelekileyo, oluneelebheli ezivulekileyo, lubhalisa ii-RRMM pts ezinemigca yonyango yangaphambili eyi-≥1 kuquka i-proteasome inhibitor (PI), kunye neyeza lokuguqula amasosha omzimba (ii-IMiD), kunye/okanye i-anti-CD38. Ii-Pts zifumene i-lymphodepletion nge-fludarabine (30 mg/m2/ngosuku) kunye ne-cyclophosphamide (300 mg/m2/ngosuku) kwiintsuku ezi-5 ukuya kwezi-3, kwaye emva koko kufakwe i-intravenous enye yeeseli ze-KQ-2003 CAR-T (ngosuku lwe-0) kumanqanaba amathathu edosi (i-DL) ngokusekelwe kuyilo oluqhelekileyo lwe-3+3: i-DL1, i-DL2, okanye i-DL3 (iiseli ze-1.0, 2.0, okanye i-3.0×106 CAR+/kg). Injongo yayikukuvavanya ukhuseleko, ukunyamezeleka, ukusebenza kakuhle kokuqala kunye neempawu ze-PK/PD, kunye nokumisela idosi ephezulu enyamezelekileyo (i-MTD), ubuthi obuncitshiswa yidosi (i-DLT). Impendulo ye-Hematological ihlolwe ngokweekhrayitheriya ze-IMWG kunye nesifo esincinci esisele (MRD) ngesizukulwana esitsha sokuhamba (NGF). I-EMD ihlolwe ngokweekhrayitheriya zempendulo ye-PET yokuHlaziya iSindululo.
Iziphumo
Ukususela ngoJulayi 25, 2024, abantu abangama-23 (52.2% besilisa; ubudala obuphakathi kweminyaka engama-64 (uluhlu lwama-52-77)) abane-RRMM bafumene i-KQ-2003 (3 DL1, 11 DL2 kunye ne-9 DL3). Ubude bokulandelela obuphakathi beenyanga ezili-13.7 (uluhlu lwama-2.1-35.2). Abantu abangama-91.3% (21/23) babene-refractory kathathu, kwaye abangama-26.1% (6/23) babene-refractory ye-penta. Ama-65.2% (15/23) ayene-cytogenetic profile enomngcipheko ophezulu/umngcipheko ophezulu.
Ama-60.9% (14/23) ee-pts ayene-EMD ekuqaleni, kuquka ii-7 ze-extramedullary extraosseous (EM-E), ii-5 ze-extramedullary-bone related (EM-B), ii-pts ezi-2 kuzo zombini.
Kwiqela le-EMD, ii-pts ezi-5 (5/14, 35.7%) azinazo izalathisi ezilinganiswayo ze-hematological, kwaye impendulo ihlolwe yi-PET-CT.
Izinga lokuphendula jikelele le-Hematological (ORR) yayiyi-100.0% (18/18), kunye nezinga le-sCR/CR eliyi-88.9% (16/18), izinga le-VGPR eliyi-11.1% (2/18). Ixesha eliphakathi ukuya kwimpendulo yokuqala yayiyi-1.2 inyanga (N=18, uluhlu 0.6–3.1; 22.2% ≤1.0 inyanga), kwaye ixesha eliphakathi ukuya kwi-CR/sCR yayiyi-2.7 inyanga (N=16, uluhlu 0.6–9.1; 50.0% ≤3.0 inyanga). Kwii-pts ezili-19 ezivavanywa yi-MRD, i-100% yayine-MRD-negative (10-5), kwaye izinga le-MRD-neg eliyi-6-mo kunye ne-12-mo ye-12 yayiyi-80.0%(8/10) kunye ne-100.0%(3/3), ngokwahlukeneyo.
I-PET ORR yee-EMD pts yayiyi-85.7%(12/14), kuquka ne-64.3%(9/14) impendulo epheleleyo ye-metabolic (CMR), i-21.4% (3/14) impendulo engaphelelanga ye-metabolic (PMR) kunye ne-14.3% (2/14) isifo se-metabolic esizinzileyo (SMD). I-64.3% (9/14) kunye ne-50.0% (7/14) yee-EMD pts yayinokunciphisa okungaphezulu kwe-50% kunye ne-75% ngobukhulu be-plasmacytomas yezicubu ezithambileyo, ngokulandelelana. Kwii-5 EMD pts ezingenazo izalathisi ezilinganiswayo ze-hematological, i-PET ORR yayiyi-80% (4/5) (2 CMR, 2 PMR kunye ne-1 SMD).
Ubude bexesha eliphakathi lokuphendula (i-DOR) abuzange bufikelelwe (NR). Amazinga okusinda okungenazo iinkqubela phambili (i-PFS) zeenyanga ezi-6 kunye namazinga okusinda ngokubanzi (i-OS) ayeyi-86.5% (73.4–100) kunye ne-86.2% (72.8–100), amazinga e-PFS yeenyanga ezili-12 kunye namazinga e-OS ayeyi-75.3% (58.4–97.0) kunye ne-86.2% (72.8–100) ngokwahlukeneyo. Amanqanaba e-PFS kunye ne-OS aphakathi ayeyi-NR.
Kufe abantu abane kuphela, kuquka ababini kuphando kwaye bavavanywa njengabanxulumene nonyango (zombini i-pneumonia enzima), kunye naba-2 abafa ngenxa ye-PD.
I-CRS kunye ne-ICANS zibonwe ngokulandelelana kwi-21/23 (91.3%, ibanga lesi-3/4 4.3%), kunye ne-5/23 (21.7%, ibanga lesi-3/4 8.7%). Ixesha eliphakathi lokuqalisa kwe-CRS yayiyi-5d (uluhlu 1–9) kunye nobude obuphakathi be-4d (uluhlu 1–15). Ixesha eliphakathi lokuqalisa kwe-ICANS yayiyi-10d (uluhlu 8–23) kunye nobude obuphakathi be-3d (uluhlu 1–9). Akukho DLTs zibonweyo.
Inombolo yekopi yeeseli ze-KQ-2003 CAR+ T (VCN) ibonise ukuba i-Tmax ephakathi yayiyi-14.0, 11.5, kunye ne-9.0 d kwi-DL1, DL2 kunye ne-DL3, ngokulandelelana. I-Cmax ephakathi yayiyi-140.6, 168.2, kunye ne-83.9 copies/ug DNA enobude obude bokuqhubeka. Phakathi kwamanqaku anokulandelelana kweenyanga ezi-6 nezili-12, ama-66.7% (10/15) kunye nama-62.5% (5/8) ayeneeseli ze-CAR+ T ezibonwayo kwigazi elingaphandle.
Izigqibo
I-BCMA/CD19 ejolise kabini kwi-CAR-T KQ-2003 ibonise impendulo yokuqala, enzulu nehlala ixesha elide kwi-RRMM ngokhuseleko olwamkelekileyo. Okubaluleke ngakumbi, ibonakalise ukusebenza okuthembisayo kwi-EMD pts, kuquka ne-EM-E enganyangekiyo yezonyango, ekufanele uphando olongezelelweyo.
Okwangoku, kukho ezinye iimvavanyo ezininzi zeklinikhi ze-CAR-T eTshayina, kwaye zikhangela izigulane. Ukuze ufumane iingcebiso ngamayeza amatsha kunye netekhnoloji, ungaqhagamshelana neSebe leMicimbi yeZibhedlele ze-Oncology zaseBeijing South Region.
Inombolo yefowuni: 4008803716
I-imeyile：myimmnet@163.com
Iireferensi
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
Ixesha leposi: Novemba-26-2024