Macallin jaamacadeed oo Ruush ah oo da'diisu tahay toddobaatameeyadii ayaa la ildaran cudurka myeloma-da badan ee horumarsan. Ka dib markii uu qaatay daawayn badan iyo laba jeer oo uu ku soo noq noqday tallaalkii autologous, wuxuu ka bartay daaweynta ugu casrisan ee ka hortagga kansarka ee CAR-T ee Shiinaha, sidaas darteed wuxuu u yimid Shiinaha si uu u helo daaweynta unugyada CAR-T waxaana si habsami leh looga saaray isbitaalka ka dib 13 maalmood oo dib loogu shubay. Diiwaankii ugu dambeeyay ee dabagalka, dhakhtarku wuxuu horey u arkay xaalad dhammaystiran oo cafis ah (CR) natiijooyinka baaritaankiisa.
Daaweynta CAR-T, ama daaweynta unugyada T-cell-ka ee soo-dhoweeyaha antigen-ka ee chimeric, waa horumar weyn oo laga sameeyay daaweynta difaaca jirka ee shaqsiga ah ee kansarka. Hawshu waxay ku lug leedahay ururinta unugyada T-ga ee bukaanka, ka dibna wax ka beddelka injineernimada hidde-sidaha ee unugyada T-ga ee in vitro ayaa la sameeyaa si kor loogu qaado awoodda unugyada T-ga si ay si gaar ah u aqoonsadaan kansarka. Unugyadan T-ga ee wax laga beddelay (tusaale ahaan, unugyada CAR-T) ayaa markaa dib loogu shubaa bukaanka.
KQ-2003 waa badeeco daaweyn ah oo laba-bartilmaameedsan oo ah unugyada CAR T-cell ee BCMA/CD19, iyadoo adeegsanaysa qaab-dhismeedka CAR ee ugu dambeeyay si kor loogu qaado dhaqdhaqaaqa unugyada iyo adkeysiga, qaab-dhismeedka CAR ee laba-geesoodka ahna wuxuu yareeyaa ka fogaanshaha antigen-ka ee daaweynta hal-bartilmaameed.
Daraasad la filayo oo uu bilaabay Baaraha (NCT04714827) oo laga sameeyay Shiinaha ayaa ujeedadeedu tahay in lagu qiimeeyo badbaadada, dulqaadka, iyo waxtarka hordhaca ah ee unugyada CAR-T ee KQ-2003 ee bukaanada (pts) ee qaba myeloma badan oo soo noqnoqda/aan la qabsan karin (RRMM), gaar ahaan kuwa qaba cudurka extramedullary (EMD).
Habka
Tijaabadan sii kordheysa ee qiyaasta ee mustaqbalka, oo leh xarumo badan, oo furan, waxay diiwaangelisaa dhibcaha RRMM oo leh ≥1 khadadka daaweynta hore oo ay ku jiraan daawada proteasome inhibitor (PI), iyo daawada immunomodulatory (IMiDs), iyo/ama anti-CD38. Pts waxay heleen lymphopletion oo leh fludarabine (30 mg/m2/maalintii) iyo cyclophosphamide (300 mg/m2/maalintii) maalmaha -5 ilaa -3, ka dibna hal irbad xididka ah oo ah unugyada KQ-2003 CAR-T (maalintii 0) saddex heer oo qiyaas ah (DL) oo ku salaysan naqshad 3+3 oo caadi ah: DL1, DL2, ama DL3 (1.0, 2.0, ama 3.0×106 unugyada CAR+/kg). Ujeeddadu waxay ahayd in la qiimeeyo badbaadada, dulqaadka, waxtarka hordhaca ah iyo astaamaha PK/PD, iyo in la go'aamiyo qiyaasta ugu badan ee la dulqaato (MTD), sunta xaddidaysa qiyaasta (DLT). Jawaabta dhiig-baxa waxaa lagu qiimeeyay iyadoo la raacayo shuruudaha IMWG iyo cudurka ugu yar ee haray (MRD) iyadoo la adeegsanayo socodka jiilka cusub (NGF). EMD waxaa lagu qiimeeyay sida ku cad Shuruudaha Jawaabta PET ee Dib-u-hagaajinta Soo-jeedinta.
Natiijooyinka
Laga bilaabo bishii Luulyo 25, 2024, 23 dhibcood (52.2% lab ah; da'da dhexe ee 64 (dhexdhexaadka ah 52-77)) oo leh RRMM waxay heshay KQ-2003 (3 DL1, 11 DL2 iyo 9 DL3). Muddada dabagalka dhexdhexaadka ah waxay ahayd 13.7 bilood (dhexdhexaadka ah 2.1-35.2). Pts waxay heleen dhexdhexaad ah 5 xariiq oo daaweyn hore ah (dhexdhexaadka ah 2-11). 91.3% (21/23) waxay ahaayeen saddex-geesood aan dib u celin karin, iyo 26.1% (6/23) oo aan dib u celin karin. 65.2% (15/23) waxay lahaayeen muuqaal cytogenetic ah oo khatar sare leh/khatar aad u sareysa.
60.9% (14/23) ee dhibcaha waxay lahaayeen EMD bilowga, oo ay ku jiraan 7 extramedullary extraosseous (EM-E), 5 extramedullary-lafo la xiriira (EM-B), 2 dhibcood oo labadaba leh.
Kooxda EMD, 5 dhibcood (5/14, 35.7%) ma laha tilmaameyaal la cabbiri karo oo ku saabsan dhiigga, jawaabtana waxaa qiimeeyay PET-CT.
Heerka jawaab celinta guud ee dhiigga (ORR) wuxuu ahaa 100.0% (18/18), iyadoo heerka sCR/CR uu ahaa 88.9% (16/18), heerka VGPR wuxuu ahaa 11.1% (2/18). Waqtiga dhexdhexaadka ah ee jawaabta koowaad wuxuu ahaa 1.2 bilood (N=18, kala duwanaanshaha 0.6–3.1; 22.2% ≤1.0 bilood), waqtiga dhexdhexaadka ah ee CR/sCR wuxuu ahaa 2.7 bilood (N=16, kala duwanaanshaha 0.6–9.1; 50.0% ≤3.0 bilood). 19 dhibcood oo la qiimeyn karo MRD, 100% waxay ahaayeen MRD-negative (10-5), heerka MRD-neg ee 6-bilood iyo 12-biloodna wuxuu ahaa 80.0% (8/10) iyo 100.0% (3/3), siday u kala horreeyaan.
PET ORR ee dhibcaha EMD waxay ahayd 85.7%(12/14), oo ay ku jiraan 64.3%(9/14) jawaab celin dhammaystiran oo dheef-shiid kiimikaad (CMR), 21.4% (3/14) jawaab celin qayb ahaan dheef-shiid kiimikaad (PMR) iyo 14.3% (2/14) cudur dheef-shiid kiimikaad oo deggan (SMD). 64.3% (9/14) iyo 50.0% (7/14) ee dhibcaha EMD waxay lahaayeen > 50% iyo > 75% hoos u dhac ku yimid cabbirka unugyada jilicsan ee plasmacytomas, siday u kala horreeyaan. 5ta dhibcood ee EMD ee aan lahayn tilmaamayaasha la cabbiri karo ee dhiigga, PET ORR waxay ahayd 80% (4/5) (2 CMR, 2 PMR iyo 1 SMD).
Muddada dhexdhexaadka ah ee jawaab celinta (DOR) lama gaarin (NR). Heerarka badbaadada aan horumarka lahayn ee 6-bilood (PFS) iyo guud ahaan badbaadada (OS) waxay ahaayeen 86.5% (73.4-100) iyo 86.2% (72.8-100), heerarka PFS iyo OS ee 12-bilood waxay ahaayeen 75.3% (58.4-97.0) iyo 86.2% (72.8-100) siday u kala horreeyaan. PFS-ka dhexdhexaadka ah iyo OS-ku waxay ahaayeen NR.
Guud ahaan 4 dhimasho ayaa dhacday, oo ay ku jiraan 2 daraasad lagu sameeyay oo lagu qiimeeyay inay la xiriiraan daaweynta (labadaba oof-wareen daran), iyo 2 dhimasho oo PD ah.
CRS iyo ICANS waxaa si kala duwan loogu arkay 21/23 (91.3%, heerka 3/4 4.3%), iyo 5/23 (21.7%, heerka 3/4 8.7%). Waqtiga dhexdhexaadka ah ee bilowga CRS wuxuu ahaa 5d (kala duwanaanshaha 1-9) iyadoo muddada dhexdhexaadka ah ay ahayd 4d (kala duwanaanshaha 1-15). Waqtiga dhexdhexaadka ah ee bilowga ICANS wuxuu ahaa 10 d (kala duwanaanshaha 8-23) iyadoo muddada dhexdhexaadka ah ay ahayd 3d (kala duwanaanshaha 1-9). Lama arag DLTs.
Lambarka nuqulka unugyada CAR+ T ee KQ-2003 (VCN) wuxuu muujiyay in dhexdhexaadka Tmax uu ahaa 14.0, 11.5, iyo 9.0 d ee DL1, DL2 iyo DL3, siday u kala horreeyaan. Cmax-ka dhexdhexaadka ah wuxuu ahaa 140.6, 168.2, iyo 83.9 nuqul/ug DNA oo leh muddo dheer oo adkeysi ah. Qodobbada la socda 6 iyo 12 bilood, 66.7% (10/15) iyo 62.5% (5/8) waxay lahaayeen unugyada CAR+ T ee la ogaan karo ee ku jira dhiigga durugsan.
Gunaanad
BCMA/CD19 oo laba-bartilmaameedsan oo CAR-T KQ-2003 ah ayaa muujisay jawaab hore, qoto dheer oo waara oo ku timid RRMM iyadoo leh badbaado la aqbali karo. Waxaa ka sii muhiimsan, waxay ku guuleysatay waxtarka wanaagsan ee EMD pts, oo ay ku jirto EM-E-ga aan la daaweyn karin ee kiliinikada, kaas oo mudan baaritaan dheeraad ah.
Waqtigan xaadirka ah, waxaa jira tijaabooyin caafimaad oo badan oo CAR-T ah oo ka jira Shiinaha, waxayna raadinayaan bukaanno. Si aad ula tashato daawooyinka cusub iyo teknoolojiyada, waxaad la xiriiri kartaa Waaxda Caalamiga ah ee Isbitaalka Oncology ee Gobolka Koonfureed ee Beijing.
Lambarka Taleefanka: 4008803716
Iimayl:myimmnet@163.com
Tixraacyada
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
Waqtiga boostada: Noofambar-26-2024