Ua loaʻa i kekahi polopeka kulanui Lūkini ma ka hopena o kona mau makahiki kanahikukūmāhiku ka maʻi myeloma holomua. Ma hope o ka loaʻa ʻana o nā lāʻau lapaʻau he nui a me ʻelua mau hoʻi hou ʻana o ka hoʻoili ʻana o ka autologous, ua aʻo ʻo ia e pili ana i ka lāʻau lapaʻau anti-cancer hou loa ʻo CAR-T ma Kina, no laila ua hele mai ʻo ia i Kina e loaʻa i ka lāʻau lapaʻau CAR-T cell a ua hoʻokuʻu maikaʻi ʻia ma hope o 13 mau lā o ka reinfusion. A ma ka moʻolelo hahai hou loa, ua ʻike mua ke kauka i kahi kūlana kala piha (CR) i kāna mau hopena hoʻokolohua.
ʻO ka lāʻau lapaʻau CAR-T, a i ʻole ka chimeric antigen receptor T-cell therapy, he holomua nui ia i ka immunotherapy cellular pilikino no ka maʻi kanesa. Pili ke kaʻina hana i ka hōʻiliʻili ʻana o nā T-cell o ka mea maʻi, a ma hope o ka hoʻololi ʻana i ka ʻenekinia genetic in vitro o nā T-cell e hoʻonui i ka hiki o nā T-cell ke ʻike pono i nā maʻi kanesa. A laila hoʻokomo hou ʻia kēia mau T-cell i hoʻololi ʻia (ʻo ia hoʻi, nā CAR-T cell) i ka mea maʻi.
ʻO KQ-2003 kahi huahana lapaʻau CAR T-cell dual-targeting BCMA/CD19, e hoʻohana ana i ka ʻōnaehana CAR parallel hou loa e hoʻonui i ka hana a me ke kūpaʻa o ke kelepona, a ʻo ka ʻōnaehana CAR pālua e hōʻoluʻolu i ka pale ʻana o ka antigen o ka lāʻau lapaʻau pahuhopu hoʻokahi.
ʻO ka pahuhopu o kahi noiʻi i hoʻomaka ʻia e ka mea noiʻi (NCT04714827) ma Kina e loiloi i ka palekana, ka hiki ke hoʻomanawanui, a me ka pono mua o nā pūnaewele KQ-2003 CAR-T i nā maʻi (pts) me ka relapsed/refractory multiple myeloma (RRMM), ʻoi aku hoʻi i ka poʻe me ka maʻi extramedullary (EMD).
ʻAno hana
ʻO kēia hoʻokolohua hoʻonui dosis, multi-center, open label, e hoʻopaʻa inoa i nā pts RRMM me ≥1 mau laina mua o ka lāʻau lapaʻau e komo pū ana me ka proteasome inhibitor (PI), a me ka lāʻau immunomodulatory (IMiDs), a/a i ʻole anti-CD38. Ua loaʻa i nā pts ka lymphodepletion me ka fludarabine (30 mg/m2/lā) a me ka cyclophosphamide (300 mg/m2/lā) i nā lā -5 a -3, a laila kahi hoʻokomo intravenous hoʻokahi o nā pūnaewele KQ-2003 CAR-T (lā 0) i ʻekolu mau pae mahele (DL) ma muli o kahi hoʻolālā maʻamau 3+3: DL1, DL2, a i ʻole DL3 (1.0, 2.0, a i ʻole 3.0 × 106 CAR+ cells/kg). ʻO ka pahuhopu ka loiloi ʻana i ka palekana, ka hoʻomanawanui, ka pono mua a me nā ʻano PK/PD, a e hoʻoholo i ka nui o ka mahele i ʻae ʻia (MTD), ka palena ʻona mahele (DLT). Ua loiloi ʻia ka pane hematological e like me nā pae hoʻohālikelike IMWG a me ka maʻi koena liʻiliʻi (MRD) e ke kahe hanauna hou (NGF). Ua loiloi ʻia ʻo EMD e like me nā pae hoʻohālikelike pane PET Refinement Proposal.
Nā Hualoaʻa
E like me ka palena lapaʻau Iulai 25, 2024, 23 mau pts (52.2% kāne; makahiki waena 64 (pae 52-77)) me RRMM i loaʻa iā KQ-2003 (3 DL1, 11 DL2 a me 9 DL3). ʻO ka lōʻihi o ka hahai ʻana he 13.7 mahina (pae 2.1-35.2). Ua loaʻa i nā Pts ka awelika o 5 mau laina mua o ka lāʻau lapaʻau (pae 2-11). 91.3% (21/23) he triple-refractory, a 26.1% (6/23) penta-refractory. 65.2% (15/23) he profile cytogenetic kiʻekiʻe/ultrahigh-risk.
He 60.9% (14/23) o nā pts i loaʻa iā EMD i ka wā mua, me 7 extramedullary extraosseous (EM-E), 5 extramedullary-bone related (EM-B), 2 pts me nā mea ʻelua.
I loko o ka hui EMD, ʻaʻohe o 5 pts (5/14, 35.7%) i nā ʻōkuhi ana koko, a ua loiloi ʻia ka pane e PET-CT.
ʻO ka helu pane holoʻokoʻa hematological (ORR) he 100.0% (18/18), me ka helu sCR/CR o 88.9% (16/18), ka helu VGPR o 11.1% (2/18). ʻO ka manawa waena i ka pane mua ʻana he 1.2 mo (N=18, pae 0.6–3.1; 22.2% ≤1.0 mo), a ʻo ka manawa waena i ka CR/sCR he 2.7 mo (N=16, pae 0.6–9.1; 50.0% ≤3.0 mo). No 19 mau pts hiki ke loiloi ʻia e MRD, 100% he MRD-negative (10-5), a ʻo ka helu 6-mo a me 12-mo MRD-neg he 80.0%(8/10) a me 100.0%(3/3), kēlā me kēia.
ʻO ka PET ORR o nā pts EMD he 85.7% (12/14), me 64.3% (9/14) ka pane metabolic piha (CMR), 21.4% (3/14) ka pane metabolic hapa (PMR) a me 14.3% (2/14) ka maʻi metabolic paʻa (SMD). 64.3% (9/14) a me 50.0% (7/14) o nā pts EMD he > 50% a me > 75% ka emi ʻana o ka nui o nā plasmacytomas ʻiʻo palupalu, kēlā me kēia. I loko o nā pts EMD 5 me ka ʻole o nā ʻōkuhi ana hematological, ʻo ka PET ORR he 80% (4/5) (2 CMR, 2 PMR a me 1 SMD).
ʻAʻole i hiki i ka manawa waena o ka pane (DOR) (NR). ʻO nā helu ola holomua ʻole (PFS) 6-mahina a me ke ola holoʻokoʻa (OS) he 86.5% (73.4–100) a me 86.2% (72.8–100), 12-mahina PFS a me nā helu OS he 75.3% (58.4–97.0) a me 86.2% (72.8–100). ʻO ka PFS waena a me OS he NR.
Ua make he 4 wale nō, me 2 i ka noiʻi ʻana a ua loiloi ʻia he pili i ka lāʻau lapaʻau (ʻo ia hoʻi ka maʻi pneumonia koʻikoʻi), a me 2 make no PD.
Ua ʻike ʻia ʻo CRS a me ICANS ma 21/23 (91.3%, papa 3/4 4.3%), a me 5/23 (21.7%, papa 3/4 8.7%). ʻO ka manawa waena i ka hoʻomaka ʻana o CRS he 5d (pae 1-9) me ka lōʻihi waena o 4d (pae 1-15). ʻO ka manawa waena i ka hoʻomaka ʻana o ICANS he 10 d (pae 8-23) me ka lōʻihi waena o 3d (pae 1-9). ʻAʻohe DLT i ʻike ʻia.
Ua hōʻike ka helu kope o nā pūnaewele CAR+ T KQ-2003 (VCN) ʻo ka median Tmax he 14.0, 11.5, a me 9.0 d ma DL1, DL2 a me DL3, kēlā me kēia. ʻO ka median Cmax he 140.6, 168.2, a me 83.9 kope/ug DNA me ka lōʻihi o ka hoʻomau ʻana. Ma waena o nā pts me 6 a me 12 mo' follow-up, 66.7% (10/15) a me 62.5% (5/8) i loaʻa nā pūnaewele CAR+ T i ʻike ʻia i loko o ke koko peripheral.
Nā hopena
Ua hōʻike ʻo BCMA/CD19 dual-targeting CAR-T KQ-2003 i ka pane mua, hohonu a paʻa hoʻi i ka RRMM me ka palekana i ʻae ʻia. ʻOi aku ka mea nui, ua hoʻokō ia i ka pono kūpono i nā pts EMD, me ka EM-E paʻakikī ke hoʻoponopono ʻia, kahi e pono ai ke noiʻi hou aku.
I kēia manawa, nui nā hoʻokolohua lapaʻau CAR-T ʻē aʻe ma Kina, a ke ʻimi nei lākou i nā maʻi. No ke kūkākūkā ʻana i nā lāʻau lapaʻau hou a me nā ʻenehana, hiki iā ʻoe ke hoʻokaʻaʻike aku i ka Beijing South Region Oncology Hospital International Department.
Helu Kelepona：4008803716
Leka uila:myimmnet@163.com
Nā Kuhikuhi
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
Ka manawa hoʻouna: Nov-26-2024