Ukuqokwa Kokwelashwa Okuphumelelayo Okuhlongozwayo Komjovo we-PA3-17 ku-T-ALL/LBL Ephinde Yaphela/Engaphenduli: Idatha Ethembisayo Yesikhathi Eside Evela Esivivinyweni Sesigaba Sokuqala kanye Namathuba Okuhlolwa Kwemitholampilo Okuqhubekayo

Ngomhlaka-7 Agasti, i-Center for Drug Evaluation (CDE) ye-National Medical Products Administration (NMPA) yamemezela ukuthi umjovo we-PA3-17 uphakanyiswe ukuthi ufakwe ekwelashweni okuphumelelayo, okuhloswe ngakho ekwelapheni iziguli ezindala ezine-T-cell acute lymphoblastic leukemia/lymphoma ephinde yabuya/engaphenduli kahle (r/r T-ALL/LBL).

Njengamanje, kusenezivivinyo eziningi zemitholampilo zobuchwepheshe obusha bokulwa nomdlavuza eShayina ezifuna iziguli. Ukubonisana ngemithi emisha kanye nobuchwepheshe, ungaxhumana noMnyango Wezizwe Ngezizwe Wesibhedlela iBeijing South Region Oncology.

Inombolo yocingo: 4008803716

I-ID ye-WeChat: 17801183037

I-imeyili：myimmnet@163.com

Iziguli ezine-T-lymphoblastic leukemia/lymphoma ephinde yabuya/engasasebenzi kahle (r/r T-ALL/LBL) zibonakaliswa ngokwezokwelapha ngokuqhubeka kwesifo ngokushesha, ukubikezela okubi kanye nokuntuleka kwezinketho zokwelapha. Njengamanje, yiNailabine kuphela eyavunyelwa yi-FDA ngo-2005 yokwelapha iziguli ze-T-ALL/LBL ezingazange zisabele okungenani emithini emibili ye-chemotherapy noma eziphinde zabuya ngemva kokwelashwa, nge-ORR engu-31% kanye ne-CR engu-23%. Ngakho-ke, kunesidingo esiphuthumayo sokuthuthukisa ezinye izindlela ezisebenzayo. Ngaphandle kokubonakaliswa kwayo kumaseli ajwayelekile e-T kanye ne-NK kanye nokungabikho kokubonakaliswa kwamanye amaseli ezicubu, i-CD7 ivezwa kakhulu kumaseli e-T-ALL/LBL. Ngakho-ke, i-CD7 ibhekwa njengenhloso engaba khona yokuthuthukiswa kokwelashwa kwe-CAR-T kwe-T-ALL/LBL. Inselele, nokho, ukugwema i-fratricide ebangelwa ukubonakaliswa kwe-CD7 kumaseli e-T. Abacwaningi basungule umjovo wamaseli e-CAR-T osuselwe kuma-antibodies e-CD7 nano, abizwa ngokuthi umjovo we-PA3-17, ngokuvimbela ukubonakaliswa kwe-molecule ye-CD7 ebusweni bamaseli e-T ngokusebenzisa i-anti-CD7 protein expression blocker (PEBL).

Idatha yokulandelela yesikhathi eside evela esivivinyweni somtholampilo seSigaba I somjovo we-PA3-17 wokwelapha i-T-cell acute lymphoblastic leukemia/lymphoma ephinde yabuya/engaphenduli (R/R T-ALL/LBL) yethulwe engqungqutheleni yezemfundo enegunya lomhlaba wonke i-EHA 2025.

Kusukela ngomhlaka-19 kuNhlolanja 2025, kwabhaliswa iziguli ezingu-13 (iziguli ezingu-3 kumthamo 1, 2, 3 eqenjini, iziguli ezingu-4 eqenjini le-RP2D), zonke ezathola ukumnika okukodwa komjovo we-PA3-17 futhi zaqeda ukuhlolwa komthamo onciphisa ubuthi (DLTs) wezinsuku ezingu-28. I-RP2D yasungulwa ku-2×10⁶ CAR-T/kg ngokusekelwe ku-pharmacokinetics, ukuphepha kanye nokusebenza kahle ngale kwalesi silinganiso. Azikho i-DLT ezenzeke futhi umthamo omkhulu obekezelelwe (MTD) awuzange ufinyelelwe. Ukusabalala kwe-Cytokine release syndrome (CRS) kwakungu-84.6% (G3:23.1%, akukho G4), kuyilapho i-immune effector cell-associated neurotoxicity syndrome (ICANS) yayinqunyelwe ku-G1-2 (15.4%). Idatha yokusebenza kahle ikhombisile ukuthi izinga lokuphendula elingcono kakhulu (ORR) lalingu-84.6% (11/13) kanti u-76.9% (10/13) uthole ukuxolelwa okuphelele/ukuxolelwa okuphelele ngokubuya kwesibalo esingaphelele (CR/CRi). Okuphawulekayo ukuthi u-69.2% (9/13, iziguli ezingu-8 CR) zigcine impendulo ezinyangeni ezi-3, kanti u-50.0% (4/8) ulondoloze i-CR＞izinyanga ezingu-15 ngemuva kokufakwa ngaphandle kokufakelwa kweseli le-stem okulandelayo (SCT), kanti ababili babo basenamangqamuzana e-CAR-T atholakalayo ezinyangeni ezingu-21. Okuphawulekayo ukuthi, isiguli eselashwe kakhulu [ngaphambi kokufakelwa kweseli le-Hematopoietic Stem Cell (HSCT), isifo esikhulu kakhulu ＞7cm] sithole i-CR ngosuku lwama-28 kanye ne-HSCT yesibili ezinyangeni ezi-6.

Umjovo we-PA3-17 ubonise ukubekezeleleka okuhle, umsebenzi ojulile noqhubekayo wezokwelapha ezigulini ze-r/r T-ALL/LBL ezelashwe kakhulu ngaphambilini, kanti ama-50% eziguli ze-CR asaphila noma/futhi angenawo umthelela wokuqhubekela phambili ngonyaka owodwa.

Njengamanje, kusenezivivinyo eziningi zemitholampilo zobuchwepheshe obusha bokulwa nomdlavuza eShayina ezifuna iziguli. Ukubonisana ngemithi emisha kanye nobuchwepheshe, ungaxhumana noMnyango Wezizwe Ngezizwe Wesibhedlela iBeijing South Region Oncology.

Inombolo yocingo: 4008803716

I-ID ye-WeChat: 17801183037

Email：myimmnet@163.com