He ahorangi whare wānanga Rūhia, kei te mutunga o ōna tau whitu tekau, e pāngia ana e te mate myeloma maha kua whanake. Whai muri i tana whiwhinga i ngā maimoatanga maha me te rua o ngā hokinga mai o te whakawhitinga pūtau autologous, ka ako ia mō te rongoā ārai-matepukupuku hou CAR-T i Haina, nō reira i haere mai ia ki Haina ki te whiwhi rongoā pūtau CAR-T, ā, i tukuna pai ia i muri i ngā rā 13 o te whakaurunga anō. Ā, i roto i ngā tuhinga whai muri hou, kua kite kē te tākuta i te āhua murunga katoa (CR) i roto i ngā hua o tana whakamātautau.
Ko te rongoā CAR-T, te rongoā pūtau-T rānei e whakamahi ana i te chimeric antigen receptor, he putanga nui i roto i te rongoā ārai mate pūtau whaiaro mō te mate pukupuku. Ko te tukanga e uru ana ki te kohikohi i ngā pūtau-T o te tūroro, ā, muri iho ka mahia ngā whakarerekētanga ira i roto i te taiwhanga o ngā pūtau-T hei whakarei ake i te kaha o ngā pūtau-T ki te kite motuhake i ngā mate pukupuku. Kātahi ka tukuna anō ēnei pūtau-T kua whakarerekētia (arā, ngā pūtau CAR-T) ki te tūroro.
Ko te KQ-2003 he hua whakaora pūtau-T CAR arotahi-rua BCMA/CD19, e whakamahi ana i te hanganga CAR whakarara hou hei whakarei ake i te mahi me te pumau o te pūtau, ā, mā te hanganga CAR takirua ka whakaiti i te karo i te mate pāwera o te whakaora ūnga kotahi.
Ko te whāinga o tētahi rangahau i tīmatahia e te Kairangahau (NCT04714827) i Haina ko te aromatawai i te haumaru, te manawanui, me te whai huatanga tuatahi o ngā pūtau KQ-2003 CAR-T i roto i ngā tūroro (pts) me te myeloma maha kua hoki mai/aukati (RRMM), inā koa ko te hunga he mate extramedullary (EMD).
Tikanga
Ko tēnei whakamātautau whakanekehanga horopeta, maha-pokapū, tuwhera tapanga, e whakauru ana i ngā tāngata RRMM me ngā raina rongoā o mua ≥1 tae atu ki te aukati proteasome (PI), me te rongoā immunomodulatory (IMiDs), me/ranei te anti-CD38. I whiwhi ngā tāngata i te lymphodepletion me te fludarabine (30 mg/m2/rā) me te cyclophosphamide (300 mg/m2/rā) i ngā rā -5 ki te -3, kātahi ka werohia kotahi te werohanga ā-uaua o ngā pūtau KQ-2003 CAR-T (rā 0) i roto i ngā taumata horopeta e toru (DL) i runga i te hoahoa paerewa 3+3: DL1, DL2, DL3 rānei (1.0, 2.0, 3.0×106 rānei ngā pūtau CAR+/kg). Ko te whāinga he aromatawai i te haumaru, te manawanui, te whai huatanga tuatahi me ngā āhuatanga PK/PD, me te whakatau i te horopeta manawanui mōrahi (MTD), te paitini whakawhāiti horopeta (DLT). I aromatawaihia te urupare toto i runga i ngā paearu IMWG me te iti rawa o te mate toenga (MRD) e te rerenga whakatupuranga hou (NGF). I aromatawaihia te EMD i runga i ngā Paearu Whakautu PET mō te Whakatikatika Tono.
Ngā Hua
I te mutunga haumanu o te 25 o Hūrae, 2024, 23 ngā tohu (52.2% tāne; te pakeke toharite 64 (te whānuitanga 52-77)) me te RRMM i whiwhi KQ-2003 (3 DL1, 11 DL2 me te 9 DL3). Ko te roanga aroturuki toharite he 13.7 marama (te whānuitanga 2.1-35.2). Kua whiwhi ngā tohu i te toharite o te 5 raina rongoā o mua (te whānuitanga 2-11). 91.3% (21/23) he ātete-toru, ā, 26.1% (6/23) he ātete-penta. 65.2% (15/23) he kōtaha cytogenetic mōrearea-tiketike/tino mōrearea-tiketike.
60.9% (14/23) o ngā tohu i pāngia e te EMD i te tīmatanga, tae atu ki te 7 o ngā tohu extramedullary extraosseous (EM-E), 5 o ngā tohu extramedullary-bone e pā ana (EM-B), 2 o ngā tohu me ngā mea e rua.
I roto i te rōpū EMD, e 5 ngā tohu (5/14, 35.7%) kāore he tohu ine toto, ā, i aromatawaitia te urupare mā te PET-CT.
Ko te tere urupare whānui o te toto (ORR) he 100.0% (18/18), me te tere sCR/CR he 88.9% (16/18), me te tere VGPR he 11.1% (2/18). Ko te wā waenga ki te urupare tuatahi he 1.2 marama (N=18, awhe 0.6–3.1; 22.2% ≤1.0 marama), ā, ko te wā waenga ki te CR/sCR he 2.7 marama (N=16, awhe 0.6–9.1; 50.0% ≤3.0 marama). O ngā tohu 19 ka taea te arotake i te MRD, 100% he MRD-neg (10-5), ā, ko te tere MRD-neg 6-marama me te 12-marama he 80.0%(8/10) me te 100.0%(3/3), ia.
Ko te PET ORR o ngā tohu EMD he 85.7% (12/14), tae atu ki te 64.3% (9/14) te urupare pākia katoa (CMR), 21.4% (3/14) te urupare pākia wāhanga (PMR) me te 14.3% (2/14) te mate pākia pumau (SMD). 64.3% (9/14) me te 50.0% (7/14) o ngā tohu EMD he > 50% me te > 75% te whakaiti i te rahi o ngā plasmacytoma kiko ngohengohe, ia. I roto i ngā tohu EMD e 5 kāore he tohu ine toto, ko te PET ORR he 80% (4/5) (2 CMR, 2 PMR me te 1 SMD).
Kāore i eke ki te roanga waenga o te urupare (DOR) (NR). Ko ngā reiti oranga kore-haere whakamua (PFS) me te oranga whānui (OS) i roto i ngā marama 6 he 86.5% (73.4–100) me te 86.2% (72.8–100), ko ngā reiti PFS me OS i roto i ngā marama 12 he 75.3% (58.4–97.0) me te 86.2% (72.8–100). Ko te PFS me te OS waenga he NR.
E whā katoa ngā matenga i puta, tae atu ki te rua i roto i te rangahau, ā, i aromatawaitia he mea e pā ana ki te rongoā (he niumōnia kino ngā mea e rua), me te rua anō hoki nā te PD.
I kitea te CRS me te ICANS i te 21/23 (91.3%, taumata 3/4 4.3%), me te 5/23 (21.7%, taumata 3/4 8.7%). Ko te wā waenga ki te tīmatanga o te CRS he 5 rā (te whānuitanga 1–9) me te roanga waenga o te 4 rā (te whānuitanga 1–15). Ko te wā waenga ki te tīmatanga o te ICANS he 10 rā (te whānuitanga 8–23) me te roanga waenga o te 3 rā (te whānuitanga 1–9). Kāore i kitea he DLT.
I whakaatuhia e te maha o ngā tārua o ngā pūtau T CAR+ KQ-2003 (VCN) ko te Tmax toharite he 14.0, 11.5, me te 9.0 rā i roto i te DL1, DL2 me te DL3. Ko te Cmax toharite he 140.6, 168.2, me te 83.9 tārua/ug DNA me te roa o te mau tonu. I roto i ngā tohu me te aroturukitanga 6 me te 12 marama, 66.7% (10/15) me te 62.5% (5/8) he pūtau T CAR+ i kitea i roto i te toto ā-taha.
Ngā Whakatau
I whakaatu te BCMA/CD19 takirua-aronga CAR-T KQ-2003 i te urupare wawe, hohonu, me te roa i roto i te RRMM me te haumaru e whakaaetia ana. Ko te mea nui ake, i whakaatuhia he whai huatanga pai i roto i ngā tohu EMD, tae atu ki te EM-E uaua ki te rongoā, e tika ana kia rangahauhia anō.
I tēnei wā, he maha atu ngā whakamātautau haumanu CAR-T i Haina, ā, kei te rapu tūroro rātou. Mō te kōrerorero mō ngā rongoā me ngā hangarau hou, ka taea e koe te whakapā atu ki te Tari Ao o te Hōhipera Oncology Rohe Tonga o Beijing.
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Īmēra：myimmnet@163.com
Ngā Tohutoro
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
Wā tuku: Whiringa-ā-rangi 26-2024