Umwarimu wo muri kaminuza y’Uburusiya uri mu kigero cy’imyaka 70 arwaye indwara ya myeloma nyinshi. Nyuma yo kuvurwa inshuro nyinshi no kongera gutera ubwoko bw’indwara inshuro ebyiri, yamenye uburyo bugezweho bwo kuvura kanseri bwa CAR-T mu Bushinwa, bityo aza mu Bushinwa guhabwa ubuvuzi bwa CAR-T cells maze avanwa mu bitaro neza nyuma y’iminsi 13 yo kongera gutera. Kandi mu nyandiko iheruka gukurikiranwa, muganga yamaze kubona ko yakize burundu (CR) mu bisubizo bye.
Ubuvuzi bwa CAR-T, cyangwa se ubuvuzi bwa chimeric antigen receptor T-cells, ni intambwe ikomeye mu buvuzi bwihariye bw’uturemangingo twa kanseri. Ubu buryo bukubiyemo gukusanya uturemangingo twa T-cells tw’umurwayi, hanyuma hagakorwa impinduka mu buryo bwa “in vitro genetic engineering” za T-cells kugira ngo hongerwe ubushobozi bwa T-cells bwo kumenya kanseri by’umwihariko. Utu turemangingo twa T-cells twahinduwe (ni ukuvuga uturemangingo twa CAR-T) twongera gukoreshwa ku murwayi.
KQ-2003 ni umuti wa BCMA/CD19 ukoresha uburyo bwa T-cells za CAR T, ukoresha imiterere ya CAR igezweho kugira ngo wongere imikorere y’uturemangingo no gukomeza kwatwo, kandi imiterere ya CAR ebyiri igabanye uburyo bwo kwirinda antigens ku miti imwe.
Inyigo yatangijwe n’Umushakashatsi (NCT04714827) mu Bushinwa igamije gusuzuma umutekano, kwihanganira, n’ubushobozi bw’ibanze bw’uturemangingo twa KQ-2003 CAR-T mu barwayi (pts) bafite myeloma nyinshi yasubiwemo/ishobora kugabanuka (RRMM), cyane cyane ku bafite indwara yo hanze ya medullary (EMD).
Uburyo
Iyi gerageza ry’igerageza ry’inyongera ry’umuti riboneka mu byiciro byinshi, rifunguye, ryerekana RRMM pts hamwe n’imirongo ≥1 y’ubuvuzi bwabanje harimo inhibitor ya proteasome (PI), n’umuti ugabanya ubukana bw’umubiri (IMiDs), cyangwa anti-CD38. Pts bahawe lymphodepletion hamwe na fludarabine (30 mg/m2/umunsi) na cyclophosphamide (300 mg/m2/umunsi) ku minsi 5 kugeza kuri 3, hanyuma hagatangwa umutsi umwe mu mitsi wa KQ-2003 CAR-T selile (umunsi 0) mu byiciro bitatu by’umuti (DL) hashingiwe ku gipimo gisanzwe cya 3+3: DL1, DL2, cyangwa DL3 (1.0, 2.0, cyangwa 3.0 × 106 CAR+ selile / kg). Intego yari ugusuzuma umutekano, kwihanganira, ubushobozi bw’ibanze n’imiterere ya PK/PD, no kumenya igipimo ntarengwa cyihanganirwa (MTD), uburozi bugabanya umuti (DLT). Ibisubizo by’amaraso byapimwe hakurikijwe ibipimo bya IMWG n’indwara ntoya zisigara (MRD) hakoreshejwe uburyo bushya bwo kuvura indwara (NGF). EMD yapimwe hakurikijwe ibipimo bya Proposal Response PET.
Ibisubizo
Kugeza ku itariki ya 25 Nyakanga 2024, amanota 23 (52.2% by'abagabo; imyaka 64 (hagati ya 52-77)) hamwe na RRMM bahawe KQ-2003 (3 DL1, 11 DL2 na 9 DL3). Igihe cyo gukurikirana cyari amezi 13.7 (hagati ya 2.1-35.2). Amasomo yari yahawe impuzandengo y'imirongo 5 ya mbere y'ubuvuzi (hagati ya 2-11). 91.3% (21/23) bari bafite impuzandengo eshatu, naho 26.1% (6/23) bafite impuzandengo ya penta. 65.2% (15/23) bari bafite impuzandengo y'ubugimbi/impanuka ikomeye cyane.
60.9% (14/23) by'udukoko twari dufite EMD mu ntangiriro, harimo 7 two mu bwoko bwa extramedullary extraosseous (EM-E), 5 two mu bwoko bwa extramedullary-bone related (EM-B), 2 twombi.
Mu itsinda rya EMD, amanota 5 (5/14, 35.7%) nta bimenyetso bipima amaraso bifite, kandi igisubizo cyasuzumwe na PET-CT.
Igipimo rusange cy’ubutabazi bw’amaraso (ORR) cyari 100.0% (18/18), hamwe n’igipimo cya sCR/CR cya 88.9% (16/18), igipimo cya VGPR cya 11.1% (2/18). Igihe cyo hagati kugeza ku gisubizo cya mbere cyari ukwezi 1.2 (N=18, hagati ya 0.6–3.1; 22.2% ≤1.0 mo), naho igihe cyo hagati kugeza ku gisubizo cya CR/sCR cyari ukwezi 2.7 (N=16, hagati ya 0.6–9.1; 50.0% ≤3.0 mo). Muri pts 19 za MRD, 100% zari MRD-negative (10-5), naho igipimo cya MRD-neg cy’amezi 6 na 12 cyari 80.0% (8/10) na 100.0% (3/3), uko bikurikirana.
PET ORR y'ibipimo bya EMD yari 85.7% (12/14), harimo 64.3% (9/14) igisubizo cyuzuye cya metabolism (CMR), 21.4% (3/14) igisubizo cy'igice cya metabolism (PMR) na 14.3% (2/14) indwara ihoraho ya metabolism (SMD). 64.3% (9/14) na 50.0% (7/14) by'ibipimo bya EMD byagabanutseho > 50% na > 75% mu bunini bwa plasmacytomas zoroshye z'uturemangingo, uko bikurikirana. Muri ibi byiciro 5 bya EMD bitarimo ibimenyetso bipima amaraso, PET ORR yari 80% (4/5) (2 CMR, 2 PMR na 1 SMD).
Igihe cyo gusubiza (DOR) nticyagezweho (NR). Igipimo cy'ubuzima budafite iterambere ry'amezi 6 (PFS) n'igipimo cy'ubuzima rusange (OS) cyari 86.5% (73.4–100) na 86.2% (72.8–100), igipimo cya PFS y'amezi 12 na OS cyari 75.3% (58.4–97.0) na 86.2% (72.8–100) uko bikurikirana. Igipimo cy'ubuzima busanzwe (PFS) na OS cyari NR.
Impfu 4 zose zabaye, harimo 2 mu bushakashatsi bwakozwe kandi bugasuzumwa nk'ubufitanye isano n'ubuvuzi (zombi zirimo umusonga ukomeye), n'izindi 2 zapfuye kubera PD.
CRS na ICANS byagaragaye muri 21/23 (91.3%, urwego rwa 3/4 4.3%), na 5/23 (21.7%, urwego rwa 3/4 8.7%). Igihe cyo hagati cya CRS cyatangiye cyari 5d (intera ya 1-9) hamwe n'igihe cyo hagati cya 4d (intera ya 1-15). Igihe cyo hagati cya ICANS cyatangiye cyari 10d (intera ya 8-23) hamwe n'igihe cyo hagati cya 3d (intera ya 1-9). Nta DLTs zagaragaye.
Umubare wa kopi y’uturemangingo twa KQ-2003 CAR+ T (VCN) wagaragaje ko igipimo cya Tmax cyari 14.0, 11.5, na 9.0 d muri DL1, DL2 na DL3, uko bikurikirana. Igipimo cya Cmax cyari kopi 140.6, 168.2, na 83.9 kuri ADN imwe kandi yamaze igihe kirekire. Mu bakurikiranye amezi 6 na 12, 66.7% (10/15) na 62.5% (5/8) bari bafite uturemangingo twa CAR+ T twashoboraga kugaragara mu maraso yo mu gice cy’imbere.
Umwanzuro
BCMA/CD19 CAR-T KQ-2003 yagaragaje igisubizo cyihuse, cyimbitse kandi kirambye muri RRMM kandi ifite umutekano ukwiye. Ikirenzeho, yagaragaje imikorere myiza mu ndwara za EMD, harimo na EM-E idakira, ikwiye gukorwaho iperereza ryimbitse.
Kuri ubu, hari andi magerageza menshi ya CAR-T mu Bushinwa, kandi barimo gushaka abarwayi. Kugira ngo ubone inama ku miti mishya n'ikoranabuhanga, ushobora kuvugana n'Ishami Mpuzamahanga ry'Ibitaro bya Oncology bya Beijing Region South.
Nimero ya Terefone: 4008803716
Imeri:myimmnet@163.com
Amareferensi
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
Igihe cyo kohereza: Ugushyingo-26-2024