Ngomhlaka-20 kuJulayi, isicelo esisha semithi(NDA) ye-pCAR-19B eyathuthukiswa ngokuzimela yi-Precision Biology yamukelwa ngokusemthethweni yi-China National Medical Products Administration (NMPA). Lo mkhiqizo uwumkhiqizo wokuqala we-CAR-T we-leukemia yezingane eShayina, osetshenziselwa ukwelapha iziguli ezineminyaka engu-3-21 ezine-CD19-positive relapsed/refractory acute lymphoblastic leukemia (ALL).
I-acute lymphoblastic leukemia (ALL) ingenye yezimila eziyingozi ezivame kakhulu ezinganeni futhi iyimbangela ehamba phambili yokufa ezinganeni nasebancane. Ukwelashwa ngamaseli e-chimeric antigen receptor (CAR-T) kushintshe kakhulu ukwelashwa kwe-relapse/refractory (R/R) B-cell ALL, ngomkhiqizo wokuqala ovunyelwe yi-FDA, i-Kymriah(tisagenlecleucel) eyasungulwa yi-Novartis, okuthuthukisa kakhulu amazinga okukhululwa kanye nezikhathi zokusinda.
I-pCAR-19B iwumkhiqizo weseli ye-CAR-T ezenzakalelayo ene-CD19-specific single-chain variable fragment (scFv) eyenziwe yaba umuntu eyenzelwe ukubhekana nezinkinga zokuphepha.
NgoNovemba 2023, i-pCAR-19B inikezwe "i-Breakthrough Therapy Designation" yi-China National Medical Products Administration yokwelapha i-B-ALL.
Imiphumela yokusebenza kahle kanye nokuphepha kwe-pCAR-19B esivivinyweni somtholampilo esibalulekile esihilela iziguli zaseShayina zezingane kanye nabantu abadala abasebasha abane-R/R B-cell ALLkwamenyezelwa ngo-Umhlangano Waminyaka Yonke Wama-66 We-American Society of Hematology (ASH).
Izindlela: Lolu cwaningo lwesigaba sesi-2 (NCT05334823) lwaluwucwaningo olunengalo eyodwa, olunelebula evulekile, olunezikhungo eziningi. Iziguli ezineminyaka engu-≥ 3 kanye no-≤ 21 ubudala ekuhlolweni nge-CD19+ R/R B-ALL eqinisekisiwe zafakwa. Isiphetho esiyinhloko kwakuyizinga lokuxolelwa eliphelele (ORR), elichazwa njenge-complete remission (CR) kanye ne-CR enokubuyiselwa kwegazi okungaphelele (CRi) zingakapheli izinyanga ezi-3 ngemuva kokufakwa.
Imiphumela: Kusukela ngomhlaka-18 Ephreli 2024, iziguli ezingu-89 zase zibhalisiwe futhi zathola i-leukapheresis, kanti iziguli ezingu-64 zathola i-pCAR-19B infusion. Azikho izimo zokwehluleka kokukhiqiza. Phakathi kweziguli ezifakwe i-infusion, u-6.25% (4/64) wayengenalo ulwazi kanti u-93.75% (60/64) wayesebuyele emigqeni eminingi yokwelashwa kwangaphambilini noma ukufakelwa kweseli le-allogeneic stem. Ubudala obumaphakathi babuyiminyaka eyi-11 (ububanzi 3-21), kanti u-56.25% (36/64) kwakungabesilisa. Ngaphezu kwalokho, u-75% (48/64) weziguli wayenezakhi zofuzo okungenani eyodwa enobungozi obukhulu. Umthwalo omaphakathi wokuqhuma komnkantsha (BM) ekuqaleni wawungu-58.3% (ububanzi 5%-98%) kanye nomthwalo osindayo wokuqhuma kwe-BM (≥50%) obonwe ku-56.25% weziguli.
Ekulandeleni okumaphakathi kwezinsuku ezingu-211 (ububanzi obungu-35-750), i-ORR engcono kakhulu yayingu-90.63% (58/64), kanti u-78.13% weziguli (50/64) ufinyelele i-CR kanye no-12.5% weziguli (8/64) ufinyelele i-CRi, okudlula ukusebenza kahle kwemikhiqizo yokwelapha ye-anti-CD19 CAR-T ebikwe ku-R/R B-ALL. U-98.27% (57/58) weziguli ezine-ORR ufinyelele ekukhululweni okungekuhle kwesifo esisele (MRD)-negative. I-ORR ezinyangeni ezi-3 yayingu-76.56% (49/64). Isikhathi esimaphakathi sempendulo (DOR) sasiyizinyanga ezingu-10.61 (95% isikhathi sokuzethemba 7.66-20.96). Isikhathi esimaphakathi sokusinda (OS) sasiyizinyanga ezingu-23.92 (95% isikhathi sokuzethemba 9.86-NR).
I-Cytokine release syndrome (CRS) kanye ne-immune effector cell-associated neurotoxicity syndrome (ICANS) zenzeka ku-98.44% kanye no-50% weziguli, ngokulandelana. I-CRS yebanga ≥3 kanye ne-ICANS zabonwa ku-29.69% kanye no-39.06% weziguli, ngokulandelana. Ubude obuphakathi be-CRS yebanga ≥3 kanye ne-ICANS babuyizinsuku ezi-4 kanye nezinsuku ezi-3, ngokulandelana. Akukho ukufa okubangelwe yi-CRS noma i-ICANS.
Iziphetho: Naphezu komthwalo osindayo wokuqhuma kwe-BM kanye nengozi ephezulu yokwehluka kwezakhi zofuzo, i-pCAR-19B ibonise amazinga aphezulu okuxolelwa, yathola izinga eliphezulu lokuxolelwa okungekuhle kwe-MRD, izimpendulo ezihlala isikhathi eside, kanye nephrofayili yokuphepha ebekezelelekayo. Lolu cwaningo lumelela isivivinyo sokuqala esibalulekile sezokwelapha se-B-ALL yobuntwana kubantu base-Asia, enikeza inketho entsha yokwelashwa kweziguli zaseShayina zezingane kanye nabantu abadala abasebasha abane-R/R B-ALL.
Njengamanje, kunezinye izivivinyo eziningi ze-CAR-T eShayina, futhi zifuna iziguli. Ukuze uthole ukubonisana ngemithi emisha kanye nobuchwepheshe, ungaxhumana noMnyango Wezizwe Ngezizwe Wesibhedlela iBeijing South Region Oncology.
Inombolo yocingo: 4008803716
I-imeyili：myimmnet@163.com
Izinkomba
1.https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d
2. http://cq.news.cn/20240728/b0a74788930d4be7a45996be2808dd4f/c.html
4.https://ash.confex.com/ash/2024/webprogram/Paper206408.html
5.https://ashpublications.org/blood/article/140/Supplement%201/4625/491174/The-Safety-and-Efficacy-of-p-CAR-19B-a-Scfv
Isikhathi sokuthunyelwe: Novemba-22-2024