Wani farfesa a jami'ar Rasha a ƙarshen shekarunsa na saba'in yana fama da cutar myeloma mai tsanani. Bayan ya yi jiyya da dama da kuma sake dawowa da dashen kansa sau biyu, ya sami labarin maganin CAR-T na zamani a China, don haka ya zo China don karɓar maganin ƙwayoyin CAR-T kuma an sallame shi lafiya bayan kwana 13 na sake haɗawa. Kuma a cikin sabon tarihin bin diddigin, likitan ya riga ya ga yanayin gafara (CR) gaba ɗaya a sakamakon bincikensa.
Maganin CAR-T, ko kuma maganin ƙwayoyin T-cell na chimeric antigen receptor, babban ci gaba ne a fannin maganin rigakafi na ƙwayoyin halitta na musamman don cutar kansa. Tsarin ya ƙunshi tattara ƙwayoyin T na majiyyaci, bayan haka ana yin gyare-gyaren injiniyan kwayoyin halitta na ƙwayoyin T a cikin vitro don haɓaka ikon ƙwayoyin T na gane cutar kansa ta musamman. Waɗannan ƙwayoyin T da aka gyara (watau, ƙwayoyin CAR-T) sannan a mayar da su ga majiyyaci.
KQ-2003 samfurin maganin ƙwayoyin T na CAR T ne mai haɗaka biyu na BCMA/CD19, yana amfani da sabon tsarin CAR mai layi ɗaya don haɓaka aikin ƙwayoyin halitta da juriya, kuma tsarin CAR guda biyu yana rage guje wa antigen na maganin manufa ɗaya.
Wani bincike da Mai Bincike Ya Fara (NCT04714827) da ake sa ran gudanarwa a China yana da nufin kimanta aminci, juriya, da kuma ingancin ƙwayoyin CAR-T na KQ-2003 a cikin marasa lafiya (pts) waɗanda suka sake dawowa/rage yawan myeloma (RRMM), musamman ga waɗanda ke da cutar extramedullary (EMD).
Hanyar
Wannan gwajin da aka yi, mai cibiya da yawa, mai buɗewa, yana nuna alamun RRMM tare da layukan magani ≥1 da suka gabata, gami da maganin hana proteasome (PI), da maganin immunomodulatory (IMiDs), da/ko anti-CD38. An sami lymphdepletion tare da fludarabine (30 mg/m2/rana) da cyclophosphamide (300 mg/m2/rana) a ranakun -5 zuwa -3, sannan a jiƙa ƙwayoyin CAR-T KQ-2003 (rana 0) a cikin jijiya guda ɗaya a cikin matakan allurai uku (DL) bisa ga ƙirar 3+3 na yau da kullun: DL1, DL2, ko DL3 (ƙwayoyin CAR+ 1.0, 2.0, ko 3.0×106/kg). Manufar ita ce a kimanta aminci, juriya, inganci na farko da halayen PK/PD, da kuma tantance matsakaicin adadin da aka jure (MTD), guba mai iyakance allurai (DLT). An tantance martanin jini bisa ga ka'idojin IMWG da kuma ƙarancin sauran cututtukan da suka rage (MRD) ta hanyar kwararar sabbin halittu (NGF). An tantance EMD bisa ga Ka'idojin Amsar PET na Gyaran Jiki.
Sakamako
Ya zuwa ƙarshen gwajin asibiti na Yuli 25, 2024, maki 23 (52.2% na maza; matsakaicin shekaru 64 (tsakanin 52-77)) tare da RRMM sun karɓi KQ-2003 (3 DL1, 11 DL2 da 9 DL3). Matsakaicin tsawon lokacin da aka bi shi shine watanni 13.7 (tsakanin 2.1-35.2). An sami matsakaicin layuka 5 na magani a baya (tsakanin 2-11). 91.3% (21/23) ba sa yin illa sau uku, kuma 26.1% (6/23) ba sa yin illa. 65.2% (15/23) suna da yanayin cytogenetic mai haɗari/mai matuƙar haɗari.
Kashi 60.9% (14/23) na pts suna da EMD a farkon, ciki har da 7 extramedullary extraosseous (EM-E), 5 extramedullary-bone related (EM-B), 2 pts tare da duka biyun.
A cikin ƙungiyar EMD, maki 5 (5/14, 35.7%) ba su da alamun auna jini, kuma an kimanta martanin ta hanyar PET-CT.
Adadin amsawar jijiyoyi gaba ɗaya (ORR) shine 100.0% (18/18), tare da ƙimar sCR/CR na 88.9% (16/18), ƙimar VGPR na 11.1% (2/18). Matsakaicin lokacin zuwa amsawar farko shine watanni 1.2 (N=18, kewayon 0.6–3.1; 22.2% ≤1.0 mo), kuma matsakaicin lokacin zuwa CR/sCR shine watanni 2.7 (N=16, kewayon 0.6–9.1; 50.0% ≤3.0 mo). Daga cikin maki 19 da za a iya kimantawa ta MRD, 100% sun kasance MRD-negative (10-5), kuma ƙimar MRD-neg na watanni 6 da 12 sune 80.0% (8/10) da 100.0% (3/3), bi da bi.
PET ORR na maki na EMD shine kashi 85.7% (12/14), gami da kashi 64.3% (9/14) cikakken amsawar metabolism (CMR), kashi 21.4% (3/14) na martanin metabolism na ɓangare (PMR) da kashi 14.3% (2/14) na cututtukan metabolism na dindindin (SMD). Kashi 64.3% (9/14) da kashi 50.0% (7/14) na maki na EMD suna da raguwar > 50% da > 75% a girman plasmacytomas na nama mai laushi, bi da bi. A cikin maki 5 na EMD ba tare da alamun auna jini ba, PET ORR shine kashi 80% (4/5) (CMR 2, PMR 2 da SMD 1).
Ba a kai matsakaicin tsawon lokacin amsawar ba (DOR) (NR). Adadin rayuwa ba tare da ci gaba ba (PFS) da jimlar rayuwa (OS) sun kasance 86.5% (73.4–100) da 86.2% (72.8–100), watanni 12 na PFS da OS sun kasance 75.3% (58.4–97.0) da 86.2% (72.8–100) bi da bi. Matsakaicin PFS da OS sune NR.
Jimillar mace-mace 4 sun faru, ciki har da 2 da aka yi nazari aka kuma tantance su a matsayin waɗanda suka shafi magani (duka ciwon huhu mai tsanani), da kuma 2 da suka mutu a PD.
An ga CRS da ICANS bi da bi a cikin 21/23 (91.3%, aji 3/4 4.3%), da 5/23 (21.7%, aji 3/4 8.7%). Matsakaicin lokacin fara CRS shine 5d (kewayon 1-9) tare da matsakaicin tsawon lokacin 4d (kewayon 1-15). Matsakaicin lokacin fara ICANS shine 10d (kewayon 8-23) tare da matsakaicin tsawon lokacin 3d (kewayon 1-9). Ba a lura da DLT ba.
Lambar kwafin ƙwayoyin CAR+ T (VCN) ta nuna matsakaicin Tmax shine 14.0, 11.5, da 9.0 a cikin DL1, DL2 da DL3, bi da bi. Matsakaicin Cmax shine 140.6, 168.2, da 83.9 kwafi/ug DNA tare da dogon lokaci na juriya. Daga cikin maki masu bin diddigin watanni 6 da 12, 66.7% (10/15) da 62.5% (5/8) suna da ƙwayoyin CAR+ T da za a iya ganowa a cikin jinin gefe.
Kammalawa
BCMA/CD19 mai haɗaka biyu CAR-T KQ-2003 ya nuna martani da wuri, mai zurfi da ɗorewa a cikin RRMM tare da aminci mai karɓuwa. Mafi mahimmanci, ya nuna tasiri mai kyau a cikin tasirin EMD, gami da EM-E mai sauƙin magancewa na asibiti, wanda ya cancanci ƙarin bincike.
A halin yanzu, akwai wasu gwaje-gwajen asibiti da yawa na CAR-T a China, kuma suna neman marasa lafiya. Don neman shawara kan sabbin magunguna da fasahohi, zaku iya tuntuɓar Sashen Kasa da Kasa na Asibitin Oncology na Yankin Kudu na Beijing.
Lambar Waya: 4008803716
Imel:myimmnet@163.com
Nassoshi
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
Lokacin Saƙo: Nuwamba-26-2024