July 25, 2021: Kite, oo ah Shirkad Gilecaad (Nasdaq: GILD), ayaa maanta ku dhawaaqday in FDA ay siisay Tecartus TM (brexucabtagene autoleucel, oo hore KTE-X19), oo ahayd tii ugu horreysay oo keliya ee la oggolaaday Chimeric antigen reseptor CAR T-cell therapy loogu talagalay daawaynta bukaanada qaangaarka ah ee dib u soo noqday ama dib u celinaya mantle lymfoma, ogolaanshaha degdega ah (MCL). FDA waxay siisay dib-u-eegis mudnaan leh iyo daawaynta horumarsan ee loogu talagalay daawayntan hal mar ah, taas oo ku saleysan natiijooyinka ZUMA-2, daraasad hal-gacan ah, calaamad-furan oo 87 boqolkiiba bukaannada ay ka jawaabeen hal faleebo oo Tecartus ah, iyadoo 62 boqolkiiba ay heleen jawaab celin dhamaystiran (CR). 18% bukaanada lagu qiimeeyay badbaadada ayaa lahaa cytokine release syndrome (CRS) ee Fasalka 3 ama ka sareeya, iyo 37% waxay lahaayeen sunta neerfaha ee Fasalka 3 ama ka sareeya.
"Inkasta oo ay jiraan horumarro rajo leh, haddana waxaa jira nusqaamo muhiim ah oo ku saabsan daaweynta bukaannada MCL kuwaas oo horumaraya daweynta bilowga ah ka dib," ayuu yiri Michael Wang, MD, ZUMA-2 Lead Investigator iyo Professor, Waaxda Lymphoma iyo Myeloma, Qeybta Daawada Kansarka, Jaamacadda Texas MD Anderson Cancer Center. "Bukaanno badan ayaa qaba cudur halis sare leh, taas oo macnaheedu yahay inay aad ugu dhowdahay inay horumaraan inkastoo daawaynta. "Tecartus waa daawaynta unugga ugu horraysa ee ay heli karaan dadka soo noqnoqda ama MCL dib u celinaya. Waxay leedahay jawaab celin cajiib ah oo ku dhow 90% iyo caddaynta hore ee bukaan-socodka waxay soo jeedinaysaa in cafisyadu ay sii socon karaan khadadka daawaynta dambe. Tani waxay ka dhigaysaa doorasho muhiim u ah bukaannadan. "
“Waxaan ku faaneynaa inaan bilowno daaweynta labaad ee unugga maxaa yeelay Kite waxaa ka go'an inuu keeno ballanqaadka Daaweynta CAR T Bukaanada qaba kansarrada dhiigbaxa,” ayuu yiri Christi Shaw, Madaxa Sare ee Kite. "Waxaan jeclaan lahaa inaan u mahadceliyo ka qaybgalayaasha daraasadda bukaan-socodka, daryeel-bixiyeyaasha, cilmi-baarayaasha caafimaadka, maamulayaasha, iyo asxaabtii Kite ee heeganka ahaa ee gacan ka geystay ansixintan, waxaana rajeyneynaa inaan la shaqeyno qanjiro bulshada si ay u keento daawayntan wax-ka-beddelka leh ee bukaannada qaba MCL soo noqnoqday ama dib u dhacsan."
Calaamadda alaabta Tecartus waxaa ku jira digniin sanduuq ah oo ku saabsan khataraha CRS iyo sunta neerfaha. FDA waxay ansixisay Qiimaynta Khatarta iyo Istaraatiijiyada Yaraynta (REMS) ee Tecartus, kaas oo lagu daray REMS ee Yescarta® (axicabtagene ciloleucel). Barnaamijka REMS waxa uu ku wargelin doonaa oo uu waxbari doonaa xirfadlayaasha daryeelka caafimaadka khataraha la xidhiidha daawaynta Tecartus, iyo tababbarka iyo shahaado-siinta barnaamijka REMS ayaa noqon doona shuruud looga baahan yahay xarumaha bixiya daawaynta Tecartus si ay u helaan oggolaanshaha kama dambaysta ah.
MCL waa nooc naadir ah qanjirada unugyada 'Hodgkin' (NHL) oo ka soo baxa unugyada qanjidhada 'mantle zone'' oo ugu horrayn saameeya ragga da'doodu ka weyn tahay 60 jir. Soo noqoshada ka dib, MCL waa mid aad u dagaal badan, bukaanno badanna way horumaraan daaweynta ka dib.
Madaxa fulinta ee Hay'adda Cilmi-baarista Lymphoma, Meghan Gutierrez, ayaa yiri, "Oggolaanshahan ayaa calaamad u ah daawaynta unug CAR T ee ugu horeysay ee loo ogolaaday lymphoma unugga mantle bukaanka waxayna u taagan tahay soohdin cusub oo daawaynta cudurkan ah." "Cilmi-baarayaashu waxay horumar weyn ka sameeyeen fahamka cudurkan tobankii sano ee la soo dhaafay, waxaana aragnay kororka tijaabooyinka bukaan-socodka, taas oo aan rajeyneyno inay sii wanaajiso xeeladaha daaweynta iyo fursadaha dadka qaba lymphoma unugga mantle. Warka maantu waxa uu dhisayaa horumarkaas oo wax bixiya unugga gogosha bukaannada iyo qoysaskoodu waxay sabab u yihiin inay rajo qabaan."
Xarunta wax soo saarka ee Kite ee El Segundo, California, ayaa soo saari doonta Tecartus. Kite waxa uu gaadhay boqolkiiba 96 heerka guusha wax soo saarka ee tijaabada ZUMA-2, oo leh wakhti wax soo saar dhexdhexaad ah oo ah 15 maalmood laga bilaabo leukapheresis ilaa gaarsiinta alaabta. Bukaanka qaba cuduro horumaray, kuwaas oo aad u xanuunsan oo halis ugu jira horumar degdeg ah, waxay u baahan yihiin xawaaraha wax soo saarka gaar ahaan.
Kite Konnect®, oo ah madal teknolojiyad isku dhafan oo bixisa macluumaad iyo caawimaad inta lagu guda jiro hawsha daweynta ee ganacsiga Kite Daaweynta CAR T, oo ay ku jirto la socodka rarida iyo cusboonaysiinta heerka wax soo saarka, ayaa diyaar u ah bukaanada xirfadahoodu daryeelka caafimaad u qoraan tecartus therapy. Kite Konnect waa nidaam taageero oo loogu talagalay bukaanada qaata Yescarta ama Tecartus, iyo sidoo kale macluumaadka kooxaha daryeelka caafimaadka ee iyaga taageeraya.
KTE-X19 ayaa hadda lagu qiimeynayaa Midowga Yurub, Wakaaladda Daawooyinka Yurubna waxay u siisay astaanta Dawooyinka Mudnaanta leh (PRIME) ee loogu talagalay MCL soo noqoshada ama diidmada leh.
Natiijooyinka tijaabada Tecartus
Oggolaanshaha Tecartus waxay ku salaysan tahay natiijooyinka tijaabada muhiimka ah ee ZUMA-2 ee socda, taas oo ah cudud keliya, daraasad summadeed oo furan. 74 bukaan oo qaan-gaar ah oo leh MCL dib u soo noqosho ama dib-u-kicin ah kuwaas oo horey u helay anthracycline-ama bendamustine-ka kooban chemotherapy, daaweynta anti-CD20 antibody, ama Bruton tyrosine kinase inhibitor ayaa lagu qoray tijaabada (ibrutinib ama acalabrutinib). Halka ugu danbeysa ee ugu danbeysa waxa ay ahayd heerka jawaabta ujeedada (ORR), kaas oo lagu qeexay sida isku darka heerka CR iyo jawaabaha qayb ka mid ah sida ay ku qiimeeyeen Gudida Madaxbanaan ee Dib u Eegista Shucaaca Sida ku xusan Kala Soocida Lugano (2014). (IRRC)
Cilmi -baarista, 87 boqolkiiba bukaannada (n = 60 lagu qiimeyn karo falanqaynta wax -ku -oolnimada) ayaa ka falceliyay hal faleebo Tecartus, iyadoo boqolkiiba 62 ay gaareen jawaab dhammaystiran. La-socodku wuxuu ahaa ugu yaraan lix bilood ka dib jawaab-celinta cudurka ee ujeeddada koowaad ee dhammaan bukaannada. Wakhtiga falcelinta dhexe weli lama go'aamin.
Tijaabada, 18% bukaannada (n=82 oo lagu qiimeeyay badbaadada) waxay lahaayeen darajada 3 ama ka sare ee CRS, halka 37% bukaanada ay qabaan dhibaatooyin neerfaha. Dhiig-yaraan, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, caabuq-pathogen aan caddayn, oof-wareen, hypocalcemia, iyo lymphopenia ayaa ahaa kuwa ugu baahsan Fasalka 3 ama saamaynta xun (10%). Istaraatiijiyada Qiimaynta Khatarta iyo Yaraynta, FDA waxay ogolaatay Tecartus (REMS). Yescarta (axicabtagene ciloleucel) iyo Tecartus (brexucabtagene autoleucelBarnaamijka REMS waxaa lagu dhex daray Tecartus REMS waxaana hadda loo yaqaan "Yescarta (axicabtagene ciloleucel) iyo Tecartus (brexucabtagene autoleucel) REMS Program"
Ku saabsan Tecartus
Tecartus waa daawaynta unug-ka-hortagga CD19 ee CAR T. Tecartus waxay isticmaashaa XLP™ habka wax soo saarka oo ay ku jiraan kobcinta unugyada T, tallaabo lagama maarmaanka u ah qaar ka mid ah unugyada B-unugyada kuwaas oo wareegga lymphoblasts ay yihiin muuqaal caadi ah. Marka lagu daro MCL, Tecartus wuxuu sidoo kale hadda ku jiraa marxaladda 1/2 ee tijaabooyinka leukemia ba'an ee lymphoblastic (ALL) iyo Cudurka sanbabada ee daba-dheeraada (CLL). Isticmaalka Tecartus ee DHAMMAAN iyo CLL waa baaritaan, badbaadadiisa iyo waxtarkeedana laguma xaqiijin noocyada kansarkan.
Tilmaamaha Tecartus
Tecartus waa CD19-ku haga hidde ahaan wax ka beddelka unugyada difaaca jirka ee T-ga oo loogu talagalay daawaynta bukaannada qaangaarka ah ee dib u soo noqday ama dib-u-celinta mantle cell lymphoma (MCL).
Tilmaamahan waxaa lagu ansixiyay oggolaansho la dardargaliyay oo ku salaysan heerka jawaabta guud iyo cimri dhererka jawaabta. Oggolaanshaha joogtada ah ee tilmaantan ayaa laga yaabaa inay ku xirnaato xaqiijinta iyo sharraxaadda faa'iidada caafimaad ee tijaabada xaqiijinta.
