Uprofesa waseyunivesithi yaseRussia oseminyakeni yakhe yokugcina yama-70 unesifo esithuthukile se-multiple myeloma. Ngemva kokwelashwa kaningi kanye nokuphinda kabili kokufakelwa kwe-autologous, wafunda ngokwelashwa kwe-CAR-T okusezingeni eliphezulu eShayina, ngakho weza eShayina ukuzothola ukwelashwa kweseli le-CAR-T futhi wakhishwa kahle ngemva kwezinsuku ezingu-13 zokufakelwa kabusha. Futhi emlandweni wakamuva wokulandelela, udokotela usevele ebone isimo sokuphulukiswa okuphelele (CR) emiphumeleni yakhe yokuhlolwa.
Ukwelashwa kwe-CAR-T, noma ukwelashwa kwe-chimeric antigen receptor T-cell, kuyindlela enkulu yokwelapha nge-immunotherapy yamaseli eyenzelwe wena uqobo lomdlavuza. Le nqubo ihilela ukuqoqwa kwama-T-cell esiguli, ngemva kwalokho kwenziwa izinguquko zobunjiniyela bezakhi zofuzo zama-T-cells ukuze kuthuthukiswe ikhono lama-T-cell lokubona ngqo umdlavuza. Lawa ma-T-cell aguquliwe (okungukuthi, amaseli e-CAR-T) abese ebuyiselwa esigulini.
I-KQ-2003 ingumkhiqizo wokwelapha we-CAR T-cell we-BCMA/CD19 oqondisa kabili, usebenzisa isakhiwo se-CAR sakamuva esihambisanayo ukuthuthukisa umsebenzi weseli kanye nokuphikelela, kanye nesakhiwo se-CAR esikabili sinciphisa ukugwema i-antigen kokwelashwa okuqondiswe okukodwa.
Ucwaningo oluqalwe yi-Investigator-Initiated (NCT04714827) eShayina luhlose ukuhlola ukuphepha, ukubekezeleleka, kanye nokusebenza kahle kokuqala kwamaseli e-KQ-2003 CAR-T ezigulini (ama-pts) ezine-relapse/refractory multiple myeloma (RRMM), ikakhulukazi kulabo abanesifo sangaphandle kwe-medullary (EMD).
Indlela
Lesi sivivinyo sokwenyusa umthamo esisezindaweni eziningi, esivulelekile, sibhalisa ama-RRMM pts anemigqa yokwelapha engu-≥1 yangaphambili okuhlanganisa i-proteasome inhibitor (PI), kanye nomuthi wokulawula amasosha omzimba (i-IMiDs), kanye/noma i-anti-CD38. Ama-Pts athole i-lymphodepletion nge-fludarabine (30 mg/m2/ngosuku) kanye ne-cyclophosphamide (300 mg/m2/ngosuku) ezinsukwini -5 kuya ku-3, bese kuba ukuminyana okukodwa kwamaseli e-KQ-2003 CAR-T (ngosuku 0) emazingeni amathathu omthamo (DL) ngokusekelwe kumklamo ojwayelekile we-3+3: i-DL1, i-DL2, noma i-DL3 (amaseli angu-1.0, 2.0, noma angu-3.0×106 CAR+/kg). Inhloso kwakuwukuhlola ukuphepha, ukubekezeleleka, ukusebenza kahle kokuqala kanye nezici ze-PK/PD, kanye nokunquma umthamo obekezelelwe kakhulu (MTD), ubuthi obukhawulela umthamo (DLT). Impendulo ye-hematological ihlolwe ngokwe-IMWG criteria kanye ne-minimum residue disease (MRD) ngokugeleza kwesizukulwane esisha (NGF). I-EMD ihlolwe ngokwe-Proposal Refinement PET Response Criteria.
Imiphumela
Kusukela ngoJulayi 25, 2024, ama-pts angu-23 (abesilisa abangu-52.2%; ubudala obuphakathi kweminyaka engu-64 (ubude obungu-52-77)) abane-RRMM bathole i-KQ-2003 (3 DL1, 11 DL2 kanye no-9 DL3). Isikhathi sokulandelela esimaphakathi sasiyizinyanga ezingu-13.7 (ubude obungu-2.1-35.2). Ama-Pts athole isilinganiso semigqa emi-5 yokwelashwa kwangaphambilini (ubude obungu-2-11). Ama-91.3% (21/23) ayene-refractory kathathu, kanti ama-26.1% (6/23) ayene-penta refractory. Ama-65.2% (15/23) ayene-cytogenetic profile enengozi ephezulu/eyingozi kakhulu.
Ama-60.9% (14/23) ama-pts ayene-EMD ekuqaleni, kufaka phakathi ama-extraosseous angu-7 angaphandle kwe-medullary (EM-E), ama-5 ahlobene ne-extramedullary-bone (EM-B), ama-pts amabili nawo womabili.
Eqenjini le-EMD, amaphuzu ama-5 (5/14, 35.7%) awanazo izinkomba ezilinganiswayo ze-hematological, futhi impendulo yahlolwa yi-PET-CT.
Izinga lokuphendula jikelele le-Hematological (ORR) lalingu-100.0% (18/18), kanye nezinga le-sCR/CR elingu-88.9% (16/18), izinga le-VGPR elingu-11.1% (2/18). Isikhathi esimaphakathi kuya empendulweni yokuqala sasingu-1.2 izinyanga (N=18, ububanzi 0.6–3.1; 22.2% ≤1.0 izinyanga), kanti isikhathi esimaphakathi kuya ku-CR/sCR sasingu-2.7 izinyanga (N=16, ububanzi 0.6–9.1; 50.0% ≤3.0 izinyanga). Kuma-pts angu-19 ahlolwa yi-MRD, u-100% wawune-MRD-negative (10-5), kanti izinga le-MRD-neg lezinyanga ezi-6 kanye nezinyanga eziyi-12 lalingu-80.0%(8/10) kanye no-100.0%(3/3), ngokulandelana.
I-PET ORR yama-EMD pts yayingu-85.7%(12/14), okuhlanganisa impendulo ephelele ye-metabolic (CMR) engu-64.3%(9/14), impendulo engaphelele ye-metabolic (PMR) engu-21.4% (3/14) kanye nesifo esizinzile se-metabolic (SMD) esingu-14.3% (2/14). Ama-64.3% (9/14) kanye nama-50.0% (7/14) ama-EMD pts ayenokwehla okungu-> 50% kanye no-> 75% ngobukhulu be-plasmacytomas yezicubu ezithambile, ngokulandelana. Kuma-5 EMD pts angenazo izinkomba ezilinganiswayo ze-hematological, i-PET ORR yayingu-80% (4/5) (2 CMR, 2 PMR kanye ne-1 SMD).
Isikhathi esimaphakathi sempendulo (i-DOR) asifinyelelwanga (NR). Amazinga okusinda okungenazo inqubekela phambili (i-PFS) yezinyanga eziyi-6 kanye namazinga okusinda okuphelele (i-OS) ayengu-86.5% (73.4–100) kanye no-86.2% (72.8–100), amazinga e-PFS yezinyanga eziyi-12 kanye ne-OS ayengu-75.3% (58.4–97.0) kanye no-86.2% (72.8–100) ngokulandelana. Amazinga e-PFS ne-OS emaphakathi ayengu-NR.
Kufe abantu abane ngokuphelele, okuhlanganisa ababili ocwaningweni futhi bahlolwa njengokuhlobene nokwelashwa (kokubili i-pneumonia enzima), kanye nababili abafa ngenxa ye-PD.
I-CRS kanye ne-ICANS zibonwe ngokulandelana ku-21/23 (91.3%, ibanga 3/4 4.3%), kanye no-5/23 (21.7%, ibanga 3/4 8.7%). Isikhathi esimaphakathi sokuqala kwe-CRS sasiyizinsuku ezi-5 (ibanga 1–9) kanye nobude obumaphakathi bezinsuku ezi-4 (ibanga 1–15). Isikhathi esimaphakathi sokuqala kwe-ICANS sasiyizinsuku ezi-10 (ibanga 8–23) kanye nobude obumaphakathi bezinsuku ezi-3 (ibanga 1–9). Azikho i-DLT ezibonwe.
Inombolo yekhophi yamaseli e-KQ-2003 CAR+ T (i-VCN) ibonise ukuthi i-Tmax ephakathi yayingu-14.0, 11.5, kanye no-9.0 ngosuku ku-DL1, DL2 kanye ne-DL3, ngokulandelana. I-Cmax ephakathi yayingu-140.6, 168.2, kanye namakhophi angu-83.9/ug DNA enokuphikelela isikhathi eside. Phakathi kwamaphuzu anokulandelela kwezinyanga ezingu-6 kanye nezingu-12, u-66.7% (10/15) kanye no-62.5% (5/8) babe namaseli e-CAR+ T atholakalayo egazini elingaphandle.
Iziphetho
I-BCMA/CD19 i-CAR-T KQ-2003 eqondiswe kabili ibonise impendulo yokuqala, ejulile nehlala isikhathi eside ku-RRMM ngokuphepha okwamukelekayo. Okubaluleke kakhulu, isebenzise ukusebenza okuthembisayo kuma-EMD pts, kufaka phakathi i-EM-E engapheli yokwelapha, okufanele ihlolwe kabanzi.
Njengamanje, kunezinye izivivinyo eziningi ze-CAR-T eShayina, futhi zifuna iziguli. Ukuze uthole ukubonisana ngemithi emisha kanye nobuchwepheshe, ungaxhumana noMnyango Wezizwe Ngezizwe Wesibhedlela iBeijing South Region Oncology.
Inombolo yocingo: 4008803716
I-imeyili：myimmnet@163.com
Izinkomba
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
Isikhathi sokuthunyelwe: Novemba-26-2024