Daaweynta Cilta-Cel ee daawaynta badan ee myeloma

Maxaa yeelay, waxa laga abuuray unugyada dhiiga cad ee la bedelay (genetically modified) si loo aqoonsado loona burburiyo unugyada myeloma badan Cilta-Cel CAR T-Cell therapy (ciltacabtagene autoleucel) way ka duwan tahay daawooyinka kale ee inta badan la isticmaalo ee kansarka (sida kiimoterabiga). 

Shirkadda Legend Biotech waxay sheegtay in FDA ay ansixisay ciltacabtagene autoleucel (cilta-cel; Carvykti) sida daawaynta loogu talagalay dadka qaangaarka ah ee leh soo noqnoqoshada ama dib-u-celinta myeloma badan kuwaas oo horey u lahaa afar ama in ka badan oo daweyn ah, sida proteasome inhibitor, wakiilka immunomodulatory, iyo anti-CD38 monoclonal antibody.

FDA waxay kordhisay muddada dib u eegista cilta-cel, daawaynta antigen receptor (CAR) T-cell oo leh laba unug ka hortag oo ka hortag ah BCMA, laga bilaabo 2021 ilaa 2023 si loo helo wakhti ku filan oo lagu baadho macluumaadka la soo gudbiyay ee ku saabsan falanqaynta la cusboonaysiiyay. habka loo sameeyay iyadoo laga jawaabayo codsiga macluumaadka FDA.

Heerka jawaab celinta guud (ORR) ee 98% (95% CI, 92.7%-99.7%) iyo heerka jawaab celinta adag ee dhamaystiran (SCR) ee 78% (95% CI, 68.8%-86.1%) ayaa lagu gaadhay cilta-cel Waxaa lagu maamulaa faleebo hal mar oo qiyaas ah 0.5 ilaa 1.0 x 106 CAR-positive T-unugyada halkii kg ee miisaanka jidhka wajiga 1/2 CARITUDE tijaabo caafimaad (NCT035 Muddada dhexdhexaadka ah ee jawaabtu waxay ahayd bilaha 21.8 (95% CI, 21.8 oo aan la qiyaasi karin) ee dabagalka dhexdhexaadka ah ee bilaha 18. 

Sundar Jagannath, MD, MBBS, borofisar ku takhasusay daawada, dhiigbaxa, iyo kansarka caafimaadka ee Mount Sinai, ayaa u adeegay sidii baaraha guud ee daraasadda. "Safarka daaweynta ee bukaanada intooda badan ee la nool myeloma badan ayaa ah wareegga aan joogtada ahayn ee dib-u-celinta iyo soo noqoshada iyada oo bukaanno yar ay helayaan jawaab-celin qoto dheer marka ay sii maraan khadadka dambe ee daaweynta," ayuu ku yiri war-saxaafadeed.

1) Natiijooyinka daraasadda CARTITUDE-1, taas oo muujisay in cilta-cel ay dhalin karto jawaabo qoto dheer oo waara iyo muddo dheer oo daaweyn la'aan ah, xitaa kuwan bukaanada badan ee myeloma ee si weyn loo daweeyay, ayaa xiiso u yeelay tani awgeed. Oggolaanshaha Carvykti maanta ayaa buuxinaysa baahida muhiimka ah ee bukaankan.

Shakhsiyaadka 97 ee leh myeloma badan oo soo noqnoqday/difaacaya ayaa ah mawduuca summada-furan, hal-gacan, daraasadda CARITUDE-da badan. Boqolkiiba bukaannada la kulma dhacdooyinka xun (AEs) iyo boqolkiiba kuwa la kulmay AE-yada daran waxay u adeegeen marxaladda 1-aad ee dhibcaha dhammaadka koowaad. ORR wuxuu u adeegay sidii marxaladda 2 ee barta ugu weyn ee dhamaadka. Cilmi-baadhayaashu waxay baareen badbaadada-horumar la'aanta (PFS), badbaadada guud (OS), waqtiga jawaabta, heerarka unugyada CAR-T, heerarka unugyada BCMA-muujinta, heerarka BCMA milmay, uruurinta cytokine nidaamka, heerarka BCMA, caafimaadka- tayada nolosha ee la xidhiidha, iyo isbeddelka aasaasiga ah ee tayada nolosha la xidhiidha caafimaadka sida dhibcaha dhamaadka labaad.

Natiijooyinka daba-galka ah ee daraasaddan oo laba sano ah ayaa dhawaan laga soo sheegay shir-sannadeedka Bulshada Maraykanka ee Hematology. Marka loo eego xogta, marka la eego waxtarka, wakhtiga dhexdhexaadka ah ee falcelinta ugu horreysa waxay ahayd 1 bil, iyo wakhtiga dhexdhexaadka ah si loo dhamaystiro jawaabta ama ka sii fiican waxay ahayd 2 bilood (qiyaastii, 1-15). Marka jiritaanka cudurka ugu yar ee haraaga ah (MRD) ee 57 bukaan ayaa la qiimeeyay, 91.8% ka mid ah ayaa tijaabiyey diidmo. Heerka PFS wuxuu ahaa 66.0% (95% CI, 54.9% -75.0%) iyo heerka OS wuxuu ahaa 80.9% (95% CI, 71.4% -87.6%) wakhtiga 18-bilood. Heerka PFS wuxuu ahaa 96.3% heerka OS-kuna wuxuu ahaa 100% kooxda bukaanada ee ku jiray MRD in ka badan 6 bilood iyo in ka badan 12 bilood. Dhexdhexaadinta PFS lama gaarin

2) Neutropenia (94.8%), dhiig-yaraan (68.0%), leukopenia (60.8%), thrombocytopenia (59.8%), iyo lymphopenia (49.5%) ayaa ka mid ahaa fasalka 3/4 dhacdooyinka xun xun ee dhiigbaxa ee la arkay. 94.8% bukaannadu waxay lahaayeen cytokine release syndrome, taas oo inta badan ka dhacday fasalada 1 iyo 2.

Calaamadda FDA-ansixisay ee cilta-cel waxay liis garaysaa Guillain-Barré syndrome, neuropathy peripheral neuropathy, curyaanka neerfaha cranial, iyo hemophagocytic lymphohistiocytosis marka lagu daro fasalka soo noqnoqda ee 3/4 AEs.

FDA waxay siisay cilta-cel horumarka iyo magacaabista agoonta ka hor inta aan loo ansixin daawaynta bukaanada qaba dib u soo noqoshada ama dib u celinta myeloma badan kuwaas oo helay afar ama in ka badan oo hore oo daawaynta ah. Cilta-cel ayaa sidoo kale loo gudbiyay si loo ansixiyo iyadoo la tixraacayo tilmaantan Yurub.

Sidee daawaynta Cilta-Cel CAR T-Cell u shaqeysaa?

Cilta-Cel therapy CAR T-cell therapy, ama chimeric antigen reseptor daawaynta, waa nooc cusub oo immunotherapy ah kaas oo isticmaala unugyada T si gaar ah loo farsameeyay si loo beegsado unugyada kansarka. Nidaamka difaaca jidhku waxa uu ka kooban yahay unugyo iyo xubno wada shaqeeya si ay jidhka uga badbaadiyaan caabuqa iyo kansarka. Unugyada T-gu waa hal nooc oo unug ka mid ah oo ugaadhsada oo dila unugyo aan dhalan, oo ay ku jiraan unugyada kansarka. Sababtoo ah unugyada kansarku waxay mararka qaarkood ka baxsan karaan nidaamka difaaca, waxaa lagama maarmaan ah in dib loo tababaro habka difaaca si loo aqoonsado oo loola dagaallamo unugyada kansarka. Daaweynta CAR T-cell waa hab cusub oo lagu tababaro habka difaaca si loola dagaallamo kansarka.

Ka dib markii muunad unugyada T-da ee bukaanka laga soo qaado dhiigga, unugyadu dib ayaa loo habeeyey si ay u yeeshaan dhismayaal gaar ah oo korkooda ah oo loo yaqaanno reseptors-kimeric antigen (CARs). Qabayayaasha unugyada CAR T waxay ka caawin karaan unugyada T inay aqoonsadaan oo weeraraan unugyada kansarka ee jirka oo dhan marka dib loogu duro bukaanka.

Daawaynta CAR T-cell hadda waxa shati ka siisay FDA oo ah heerka daryeelka noocyada soo noqoshada ama dib u laabashada qaarkood. Liin-dhiska non-Hodgkin, Multi myeloma, iyo cudurada carruurta oo soo laba kacleeyay lymphoblastic leukemia ba'an (ALL), waxaana lagu tijaabiyaa noocyo dheeraad ah oo kansarka dhiigga ah.

CAR T-Cell therapy waa nooc ka mid ah daaweynta difaaca jirka oo adeegsata unugyada T-unugyada si gaar ah loo hagaajiyay kuwaas oo qayb ka ah habka difaaca jidhkeena si loola dagaallamo. kansarka. Muunad ka mid ah unugyada T ee bukaannada ayaa laga soo ururiyaa dhiigga, ka dibna waa la beddelaa si ay u soo saaraan dhismayaal gaar ah oo loo yaqaan 'chimeric antigen receptors' (CAR) oo korkooda ah. Marka unugyada CAR ee la beddelay dib loogu celiyo bukaanka, unugyadan cusub waxay weeraraan antigen-ka gaarka ah waxayna dilaan unugyada burooyinka.

Waa maxay qiimaha Cilta-Cel CAR T-Cell therapy?

Waqtigan xaadirka ah, Cilta-Cel CAR T-Cell therapy waa ku dhawaad ​​$225,000 USD Shiinaha iyo $425,000 USD gudaha Maraykanka. Hadda, waxa laga heli karaa xarumaha la doortay ee Maraykanka. Si kastaba ha ahaatee, tijaabooyin badan oo caafimaad ayaa ka socda Shiinaha, waxaana la filayaa in kharashkooda uu si weyn hoos ugu dhaco marka tijaabooyinkan cusub la ansixiyo.

Dhibaatooyinka ay keento Cilta-Cell CAR T-Cell therapy

Cilta-Cel (ciltacabtagene autoleucel) waxay keeni kartaa waxyeelo aad u daran ama nafta halis gelisa oo keeni karta dhimasho. Wac daryeel bixiyahaaga ama hel gargaar degdeg ah isla markaaba haddii aad hesho mid ka mid ah kuwan soo socda:

• qandho (100.4°F/38°C ama ka sareeya)
• qarqaryo ama gariir
• wadna garaacid ama aan joogto ahayn
• neefsashada oo adkaata
• cadaadis dhiig oo aad u hooseeya
• dawakhaad/ madax iftiin
• Saamaynta habdhiskaaga neerfayaasha, kuwaas oo qaarkood ay dhici karaan maalmo ama toddobaadyo ka dib markaad hesho faleebo oo laga yaabo inay marka hore noqdaan kuwo khiyaano leh, sida:
  • Dareen jahawareer, foojignaan yar ama jaahwareer, hadal oo ku adag ama hadalka qallafsan, akhriska oo ku adag, qorista iyo fahamka erayada, xusuusta oo lumis
  • luminta isuduwidda ee saameeya dhaqdhaqaaqa iyo dheelitirka, dhaqdhaqaaqyada tartiib tartiib ah, isbeddelka qoraalka gacanta
  • isbeddellada shakhsiyadeed, oo ay ku jiraan hoos u dhigista awoodda muujinta shucuurta, hadalka oo yaraada, xiiso la'aanta hawlaha, iyo hoos u dhigidda muujinta wejiga
  • xiirid, kabuubyo iyo xanuun gacmaha iyo cagaha, socodka oo ku adkaata, lug iyo/ama cudud daciifnimo, iyo neefsashada oo ku adkaata
  • kabuubyo wajiga ah, dhaqdhaqaaqa muruqyada wejiga iyo indhaha oo ku adkaata

Cilta-Cel CAR T-Cell therapy ee Shiinaha

Xeer-ilaaliyeyaasha Shiinaha waxay siiyeen heerka daawaynta horumarsan ee Legend Biotech iyo Janssen's baadhista CAR T-cell therapy, ciltacabtagene autoleucel (cilta-cel), sida daawaynta suurtagalka ah ee soo noqoshada ama dib u laabashada myeloma badan.

Cilta-cel waxa loola jeedaa labada JNJ-4528, oo ah magaca daawaynta looga aqoonsaday meel ka baxsan Shiinaha, iyo LCAR-B38M, oo ah magaca looga yaqaan Shiinaha.

Xarunta Shiinaha ee Qiimaynta Maandooriyaha (CDE) ee Maamulka Alaabooyinka Caafimaadka Qaranka (NMPA) ayaa loogu talagalay in lagu dedejiyo horumarinta iyo dib u eegista daawaynta oo leh caddayn caafimaad oo hordhac ah oo ballanqaad ka weyn daawaynta hadda jirta ee cudurrada halista ah.

Sida laga soo xigtay war-saxaafadeed ka soo baxay Legend, CEO Frank Zhang, PhD, "Naqdinta nashqadeynta ee ay ku talisay Shiinaha CDE ee NMPA waxay muujineysaa guul muhiim ah oo sharciyeynta horumarinta dheeraadka ah ee cilta-cel ee bukaannada myeloma badan."

Wuxuu sii waday, "Halyeeyadku waxay sii wadi doonaan sahaminta daaweyntan baadhista ee Shiinaha iyo dibadda iyada oo lala kaashanayo Janssen.

Daawaynta ayaa hore u haysatay shahaadada PRIME (Daawoyinka mudnaanta leh) ee Hay'adda Daawooyinka Yurub si isku mid ah tilmaam iyo daawaynta horumarsan ee laga soo qaatay Maamulka Cuntada iyo Dawooyinka ee Maraykanka. Hay'adaha sharciyeynta ee Maraykanka, EU, Japan, iyo Kuuriya ayaa sidoo kale u kala saaray sida daroogada agoonta ah.