Ib tug xib fwb qhia ntawv hauv tsev kawm ntawv Lavxias uas muaj hnub nyoog xya caum xyoo raug mob qog nqaij hlav ntau yam mob myeloma. Tom qab kho ntau zaus thiab rov qab muaj ob zaug ntawm kev hloov pauv tus kheej, nws tau kawm txog kev kho mob qog nqaij hlav CAR-T tshiab hauv Suav teb, yog li nws tuaj rau Suav teb kom tau txais kev kho mob CAR-T cell thiab tau tawm hauv tsev kho mob tau zoo tom qab 13 hnub ntawm kev rov ua dua tshiab. Thiab hauv cov ntaub ntawv soj ntsuam tshiab tshaj plaws, tus kws kho mob twb pom tias nws tau zoo tag nrho (CR) hauv nws cov txiaj ntsig kuaj mob.
Kev kho mob CAR-T, lossis kev kho mob chimeric antigen receptor T-cell, yog ib qho kev tshawb pom loj hauv kev kho mob qog noj ntshav uas siv tus kheej. Cov txheej txheem no suav nrog kev sau cov T-cell ntawm tus neeg mob, tom qab ntawd kev hloov kho caj ces ntawm T-cell hauv vitro tau ua kom cov T-cell muaj peev xwm paub txog qog noj ntshav. Cov T-cell uas tau hloov kho no (piv txwv li, CAR-T cell) ces raug xa rov qab rau tus neeg mob.
KQ-2003 yog BCMA/CD19 dual-targeting CAR T-cell therapy khoom, siv cov qauv CAR sib luag tshiab los txhim kho cov haujlwm ntawm lub hlwb thiab kev ua haujlwm ntev, thiab cov qauv CAR ob npaug txo qhov kev zam ntawm cov antigen ntawm ib lub hom phiaj kho mob.
Ib txoj kev tshawb nrhiav uas tau pib los ntawm tus kws tshawb nrhiav (NCT04714827) hauv Suav teb lub hom phiaj yog los ntsuam xyuas kev nyab xeeb, kev kam rau siab, thiab kev ua haujlwm zoo ntawm KQ-2003 CAR-T hlwb hauv cov neeg mob (pts) uas muaj mob relapsed/refractory multiple myeloma (RRMM), tshwj xeeb tshaj yog rau cov neeg uas muaj mob extramedullary (EMD).
Txoj Kev
Qhov kev sim tshuaj no, ntau lub chaw, qhib daim ntawv lo, thiab nce koob tshuaj, sau npe rau RRMM pts nrog ≥1 kab kev kho mob yav dhau los suav nrog proteasome inhibitor (PI), thiab tshuaj immunomodulatory (IMiDs), thiab/lossis anti-CD38. Pts tau txais lymphodepletion nrog fludarabine (30 mg/m2/hnub) thiab cyclophosphamide (300 mg/m2/hnub) rau hnub -5 txog -3, thiab tom qab ntawd ib zaug txhaj tshuaj ntawm KQ-2003 CAR-T hlwb (hnub 0) hauv peb qib koob tshuaj (DL) raws li tus qauv 3+3 tsim: DL1, DL2, lossis DL3 (1.0, 2.0, lossis 3.0 × 106 CAR+ hlwb/kg). Lub hom phiaj yog los ntsuam xyuas kev nyab xeeb, kev kam rau siab, kev ua haujlwm ua ntej thiab cov yam ntxwv PK/PD, thiab txiav txim siab qhov siab tshaj plaws koob tshuaj kam rau siab (MTD), koob tshuaj txwv kev lom (DLT). Kev teb ntawm cov ntshav tau raug soj ntsuam raws li cov qauv IMWG thiab cov kab mob tsawg kawg nkaus (MRD) los ntawm cov kab mob tshiab (NGF). EMD tau raug soj ntsuam raws li Cov Qauv Teb Rov Qab PET.
Cov txiaj ntsig
Txij li thaum Lub Xya Hli 25, 2024 kev txiav txim siab hauv kev kho mob, 23 pts (52.2% txiv neej; hnub nyoog nruab nrab 64 (ntau yam 52-77)) nrog RRMM tau txais KQ-2003 (3 DL1, 11 DL2 thiab 9 DL3). Lub sijhawm saib xyuas nruab nrab yog 13.7 mo (ntau yam 2.1-35.2). Pts tau txais nruab nrab ntawm 5 kab kev kho mob yav dhau los (ntau yam 2-11). 91.3% (21/23) yog triple-refractory, thiab 26.1% (6/23) penta-refractory. 65.2% (15/23) muaj cov qauv cytogenetic muaj kev pheej hmoo siab / ultrahigh-risk.
60.9% (14/23) ntawm cov pts muaj EMD thaum pib, suav nrog 7 extramedullary extraosseous (EM-E), 5 extramedullary-bone related (EM-B), 2 pts nrog ob qho tib si.
Hauv pawg EMD, 5 pts (5/14, 35.7%) tsis muaj cov cim qhia txog ntshav, thiab cov lus teb tau raug soj ntsuam los ntawm PET-CT.
Tus nqi teb tag nrho ntawm cov ntshav (ORR) yog 100.0% (18/18), nrog rau tus nqi sCR/CR ntawm 88.9% (16/18), tus nqi VGPR ntawm 11.1% (2/18). Lub sijhawm nruab nrab rau thawj qhov kev teb yog 1.2 lub hlis (N = 18, ntau yam 0.6–3.1; 22.2% ≤1.0 lub hlis), thiab lub sijhawm nruab nrab rau CR/sCR yog 2.7 lub hlis (N = 16, ntau yam 0.6–9.1; 50.0% ≤3.0 lub hlis). Ntawm 19 MRD-evaluable pts, 100% yog MRD-negative (10-5), thiab 6-hli thiab 12-hli MRD-neg tus nqi yog 80.0% (8/10) thiab 100.0% (3/3), raws li.
Tus PET ORR ntawm EMD pts yog 85.7% (12/14), suav nrog 64.3% (9/14) kev teb metabolic tiav (CMR), 21.4% (3/14) kev teb metabolic ib nrab (PMR) thiab 14.3% (2/14) kab mob metabolic ruaj khov (SMD). 64.3% (9/14) thiab 50.0% (7/14) ntawm EMD pts muaj > 50% thiab > 75% txo qis hauv qhov loj ntawm cov nqaij mos plasmacytomas, raws li. Hauv 5 EMD pts tsis muaj cov ntsuas hematological, PET ORR yog 80% (4/5) (2 CMR, 2 PMR thiab 1 SMD).
Lub sijhawm nruab nrab ntawm kev teb (DOR) tsis tau mus txog (NR). Cov nqi ciaj sia nyob 6-hli tsis muaj kev nce qib (PFS) thiab tag nrho cov ciaj sia nyob (OS) yog 86.5% (73.4–100) thiab 86.2% (72.8–100), 12-hli PFS thiab OS nqi yog 75.3% (58.4–97.0) thiab 86.2% (72.8–100) raws li. Cov nqi PFS thiab OS nruab nrab yog NR.
Tag nrho muaj 4 tus neeg tuag, suav nrog 2 tus neeg raug tshawb fawb thiab ntsuas tias yog kev kho mob (ob qho tib si mob ntsws hnyav), thiab 2 tus neeg tuag rau PD.
CRS thiab ICANS tau pom nyob rau hauv 21/23 (91.3%, qib 3/4 4.3%), thiab 5/23 (21.7%, qib 3/4 8.7%). Lub sijhawm nruab nrab kom CRS pib yog 5d (ntau yam 1–9) nrog lub sijhawm nruab nrab ntawm 4d (ntau yam 1–15). Lub sijhawm nruab nrab kom ICANS pib yog 10 d (ntau yam 8–23) nrog lub sijhawm nruab nrab ntawm 3d (ntau yam 1–9). Tsis muaj DLTs tau pom.
Tus lej theej ntawm cov hlwb CAR+ T ntawm KQ-2003 (VCN) qhia tau tias qhov nruab nrab ntawm Tmax yog 14.0, 11.5, thiab 9.0 hnub hauv DL1, DL2 thiab DL3, raws li. Qhov nruab nrab ntawm Cmax yog 140.6, 168.2, thiab 83.9 daim theej/ug DNA nrog lub sijhawm ntev. Ntawm cov pts nrog 6 thiab 12 lub hlis kev saib xyuas, 66.7% (10/15) thiab 62.5% (5/8) muaj cov hlwb CAR+ T uas pom tau hauv cov ntshav ncig.
Cov Lus Xaus
BCMA/CD19 ob lub hom phiaj CAR-T KQ-2003 tau qhia txog kev teb thaum ntxov, tob thiab ruaj khov hauv RRMM nrog kev nyab xeeb txaus. Qhov tseem ceeb tshaj, nws tau ua haujlwm zoo hauv EMD pts, suav nrog kev kho mob EM-E, uas tsim nyog tshawb nrhiav ntxiv.
Tam sim no, muaj ntau lwm yam kev sim tshuaj CAR-T hauv Suav teb, thiab lawv tab tom nrhiav cov neeg mob. Yog xav tau kev sab laj txog cov tshuaj tshiab thiab cov thev naus laus zis, koj tuaj yeem tiv tauj Beijing South Region Oncology Hospital International Department.
Xov Tooj: 4008803716
Email:myimmnet@163.com
Cov ntaub ntawv siv los ua piv txwv
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
Lub sijhawm tshaj tawm: Kaum Ib Hlis-26-2024