Maarso 2022: Sida laga soo xigtay Johnson & Johnson, daawayn ay sameeyeen shirkadda iyo la-hawlgalkeeda Shiinaha ku salaysan Hal qayb oo ka mid ah Legend Biotech Corp in lagu daweeyo nooc ka mid ah kansarka unugyada dhiiga cad waxa ogolaaday Maamulka Cuntada iyo Dawooyinka ee Maraykanka.
The FDA’s decision clears the way for Legend’s first product to be approved in the United States, at a time when the agency has increased its scrutiny of medication trials done in China. The Legend-J&J treatment was first tried in China, then in the United States and Japan.
Daawaynta, Carvykti/Cilta-cel, waxay ka tirsan tahay fasalka daawooyinka loo yaqaan CAR-T therapies, ama chimeric antigen receptor T-cell therapies. CAR-T medicines work by extracting and genetically modifying a patient’s own disease-fighting T-cells to target specific proteins on cancer cells, then replacing them to seek out and attack cancer.
Legend iyo J&J waxay ku iibin doonaan daroogada Shiinaha Greater 70-30 kala qaybsanaanta faa'iidada, iyo dhammaan waddamada kale ee 50-50 kala qaybsanaanta faa'iidada.
February 28, 2022-Shirkadda Legend Biotech Corporation waxay ku saleysantahay Maraykanka., a global biotechnology company developing, manufacturing and commercializing novel therapies to treat life-threatening diseases, today announced that the U.S. Food and Drug Administration (FDA) has approved its first product, CARVYKTI™(ciltacabtagene autoleucel; ciltacel), for the treatment of adults with relapsed or refractory multiple myeloma (RRMM) who have received four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Legend Biotech entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. (Janssen) to develop and commercialize ciltacel in December 2017.
CARVYKTITM waa daawaynta chimeric antigen receptor T-cell (CAR-T) oo leh laba B-cell maturation antigen (BCMA) -bartilmaameedka hal domain
unugyada difaaca jirka oo la siiyo faleebo hal mar ah oo leh qiyaas lagu taliyey oo u dhexeeya 0.5 ilaa 1.0 x 106 CAR-positive T unugyada T ee kiilo kasta oo miisaanka jidhka ah. Daraasada muhiimka ah ee CARTITUDE-1, jawaabo qoto dheer iyo kuwo waara ayaa lagu arkay bukaanada qaba RRMM (n=97), oo leh heerar guud oo jawaab celin ah (ORR) ee 98 boqolkiiba (95 boqolkiiba kalsoonida [CI]: 92.7-99.7) oo ay ku jiraan 78 boqolkiiba bukaanada ayaa si adag u gaadha
jawaab celin dhamaystiran (sCR, 95 boqolkiiba CI: 68.8-86.1).
1 Dhexdhexaadinta bilaha 18 ee dabagalka, muddada dhexe ee jawaabta (DOR) waxay ahayd 21.8 bilood (95 boqolkiiba CI 21.8-lama qiyaasi karo).
1
CARVYKTI™ waxaa lagu heli karaa oo keliya iyada oo loo marayo barnaamijka xaddidan ee hoos yimaada Istaraatiijiyada Qiimaynta iyo Khatarta (REMS) ee loo yaqaan CARVYKTI™
REMS Program
Saamaynta Unugyada Isku-xidhka Neurotoxicity Syndrome (ICANS), Parkinsonism iyo Guillain-Barré syndrome, hemophagocytic
lymphohistiocytosis/makrophage activation syndrome (HLH/MAS), iyo cytopenia daba-dheer iyo/ama soo noqnoqda.
1 Digniin iyo taxaddar
Waxaa ka mid ah cytopenia oo soo noqnoqda oo soo noqnoqda, caabuqa, hypogammaglobulinemia, dareen-celinta xasaasiyadeed, cudurrada labaad iyo
saamaynta ku leh awoodda wadista iyo isticmaalka mishiinada.
1 Dareen-celinta xun ee ugu caansan (≥20 boqolkiiba) waa pyrexia, CRS,
hypogammaglobulinemia, hypotension, murqo xanuun, daal, caabuq-pathogen aan la cayimin, qufac, qarqaryo, shuban, lallabo, encephalopathy, rabitaanka cuntada oo yaraada, infekshanka sare ee neef-mareenka, madax-xanuun, tachycardia, dawakhaad, dyspnea, barar, caabuq viral, coagulopathy, calool-istaagga, iyo matagid.
“Multiple myeloma remains an incurable disease with heavily pretreated patients facing poor prognoses with limited treatment options,” said Ying Huang, PhD, CEO and CFO of Legend Biotech. “Today’s approval of CARVYKTI is a pivotal moment for Legend Biotech because it
waa ogolaanshaha suuqgeyneed ee ugu horeysay abid, laakiin waxa runtii nagu xiiso galiyay waa awooda dawada si ay u noqoto ikhtiyaar daawaynta saamaynta leh ee bukaanada u baahan muddo dheer oo aan daawayn lahayn. Tani waa tii ugu horreysay ee daawaynta unugga badan ee aanu qorsheynayno inaan u keeno bukaannada inta aan sii wadno horumarinta dhuumahayaga gobollada cudurrada."
Multiple myeloma waxay saamaysaa nooca unugyada dhiigga cad ee loo yaqaanno plasma cells, kuwaas oo laga helo dhuuxa lafta.2 Inta badan bukaannada
soo noqoshada ka dib marka la maro daawaynta hore oo wajahdo saadaal xumo ka dib daawaynta saddex nooc oo waaweyn oo daroogo ah, oo ay ku jiraan
wakiilka immunomodulatory, proteasome inhibitor ah iyo anti-CD38 monoclonal antibody.3,4,5
“The treatment journey for the majority of patients living with multiple myeloma is a relentless cycle of remission and relapse with fewer patients achieving a deep response as they progress through later lines of therapy,” said Dr. Sundar Jagannath, MBBS, Professor of Medicine, Hematology and Medical Oncology at Mount Sinai, and principal study investigator. “This is why I have been really excited about the results from the CARTITUDE-1 study, which has demonstrated that cilta-cel can provide deep and durable responses and long-term
muddooyin daweyn-la'aan ah, xitaa marka lagu jiro bukaannada badan ee myeloma ee aadka loo sii daweeyay. Oggolaanshaha maanta ee CARVYKTI waxay gacan ka geysaneysaa wax ka qabashada baahida weyn ee aan la daboolin ee bukaannadan."
Dawo la gaaryeelay ahaan, maamulka CARVYKTI™ wuxuu u baahan yahay tababaro, diyaargarow, iyo shahaado si loo hubiyo khibrad aan kala go 'lahayn ee bukaanka. Iyadoo loo marayo hab weji leh, Legend iyo Janssen waxay hawlgelin doonaan shabakad xaddidan oo xarumo daawaynta shahaadaysan sida
Waxay ka shaqeeyaan si ay u cabbiraan awoodda wax soo saarka oo ay kordhiyaan helitaanka CARVYKTI ™ ee Maraykanka oo dhan 2022 iyo wixii ka dambeeya, hubinta in daawaynta CARVYKTI ™ la siin karo dhakhaatiirta kansarka iyo bukaankooda hab la isku halayn karo iyo waqti.
About CARVYKTI™ (Ciltacabtagene autoleucel; cilta-cel) CARVYKTI™ is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient’s own T cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells that express BCMA. BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B-cells and plasma cells. The CARVYKTI™ CAR protein features two BCMA-targeting single domain antibodies designed to confer high avidity against human BCMA. Upon binding to
Unugyada BCMA-muujinta, CAR waxay kor u qaadaa firfircoonida unugyada T-unugga, ballaarinta, iyo baabi'inta unugyada bartilmaameedka ah.
Bishii Disembar 2017, Shirkadda Legend Biotech waxay la gashay shati caalami ah oo gaar ah iyo heshiis iskaashi oo ay la gashay Janssen Biotech, Inc. si ay u horumariso oo ay ganacsi uga samayso cilta-cel.
Bishii Abriil 2021, Legend wuxuu ku dhawaaqay soo gudbinta Codsiga Oggolaanshaha Suuqgeynta ee Wakaaladda Daawooyinka Yurub oo raadinaysa oggolaanshaha cilta-cel ee daaweynta bukaannada soo noqnoqda iyo/ama qaboojiyeyaasha badan ee myeloma. Marka lagu daro Magacaabista Daawaynta Horumarka Mareykanka ee la bixiyay Diseembar 2019, cilta-cel waxay heshay Magacaabista Daawaynta Horumarka ee Shiinaha Agoosto 2020. Cilta-cel sidoo kale waxay FDA ka heshay Magacaabista Daroogada Agoonta bishii Febraayo 2019, iyo Guddiga Yurub Febraayo 2020 .
Ku saabsan CARTITUDE-1 Daraasadda
CARTITUDE-1 (NCT03548207) waa marxalad socota 1b/2, sumad furan, hal cudud, tijaabo xarun badan oo lagu qiimeeyo cilta-cel daaweynta bukaanada qaangaarka ah ee leh soo noqnoqda ama dib u laabashada myeloma badan, kuwaas oo hore u helay ugu yaraan saddex sadar oo hore daawaynta oo ay ku jiraan proteasome inhibitor (PI), wakiilka immunomodulatory (IMiD) iyo anti-CD38 monoclonal antibody. 97 ka mid ah bukaannada isdiiwaangeliyay
Tijaabada, 99 boqolkiiba waxay ahaayeen kuwo ka soo horjeeda khadka ugu dambeeya ee daaweynta iyo 88 boqolkiiba waxay ahaayeen saddex-fasalka refractory, taasoo la micno ah in kansarku uusan ka jawaabin, ama uusan ka jawaabin, IMiD, PI iyo anti-CD38 monoclonal antibody.1
Waxtarka muddada dheer iyo astaanta badbaadada ee cilta-cel ayaa lagu qiimeeyay daraasadda CARTITUDE-1 ee socota, iyadoo natiijooyin laba sano ah oo dabagal ah dhowaan lagu soo bandhigay ASH 2021.6
Ku saabsan Multiple Myeloma
Multiple myeloma waa kansar dhiig oo aan dawo lahayn oo ka bilaabma dhuuxa lafta waxaana lagu gartaa kororka xad-dhaafka ah ee unugyada balaasmaha.
2022, waxaa lagu qiyaasaa in in ka badan 34,000 oo qof laga heli doono cudurka 'multiple myeloma', in ka badan 12,000 oo qofna
u dhinta cudurka gudaha Maraykanka
7 Iyadoo qaar ka mid ah bukaanada qaba myeloma badan aysan lahayn wax calaamado ah, bukaanada intooda badan waa la ogaadaa sababtoo ah
calaamadaha ay ka mid yihiin dhibaatooyinka lafaha, hoos u dhaca tirada dhiigga, kor u kaca calcium, dhibaatooyinka kelyaha ama caabuqyada.
8 Inkastoo daawaynta laga yaabo
natiija cafis, nasiib daro, bukaanku waxay u badan tahay inay soo noqdaan.
3 Bukaannada soo noqda ka dib daawaynta caadiga ah, oo ay ku jiraan protease inhibitors, wakiilada immunomodulatory, iyo anti-CD38 monoclonal antibody, waxay leeyihiin saadaasha liidata iyo dhawr ikhtiyaar oo daaweyn ah oo la heli karo.
CARVYKTI™ Macluumaadka Badbaadada Muhiimka ah ee Tilmaamaha iyo Isticmaalka
CARVYKTI (ciltacabtagene autoleucel) waa B-cell maturation antigen (BCMA) -hagaha hidde ahaan wax laga beddelay autologous T-unuga immunotherapy oo lagu tilmaamay daawaynta bukaanada qaangaarka ah ee soo noqnoqda ama soo noqnoqda ee myeloma badan, ka dib afar ama in ka badan oo daawaynta ka hor, oo ay ku jiraan proteasome inhibitor, wakiilka immunomodulatory, iyo anti-CD38 monoclonal antibody.
DIGNIIN: CYTOKINE SYNDROME SYNDROME, SUNOOYINKA NUUROLOJIGA, HLH/MAS, iyo raagtay oo soo noqnoqonaysa
CYTOPENIA
• Cytokine Release Syndrome (CRS), oo ay ku jiraan falcelinno dhimasho ama nafta-halis ah, ayaa ku dhacay bukaannada ka dib daawaynta
CARVYKTI™. Ha siin CARVYKTI™ bukaanka qaba caabuq firfircoon ama xanuunada bararka. Ku dawee CRS daran ama nafta halis gelisa tocilizumab ama tocilizumab iyo corticosteroids.
• Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), kaas oo noqon kara mid dilaa ah ama nafta halis gelisa, ayaa dhacay
daawaynta CARVYKTI™, oo ay ku jirto ka hor bilawga CRS, isla markaaba CRS, xalinta CRS ka dib, ama maqnaanshaha CRS. La soco dhacdooyinka neerfaha ka dib daawaynta CARVYKTI™. Bixi daryeel taageero iyo/ama corticosteroids haddii loo baahdo.
• Parkinsonism iyo Guillain-Barré syndrome iyo dhibaatooyinkooda la xidhiidha ee keena falcelinno dhimasho ama nafta halis gelisa
dhacay ka dib daawaynta CARVYKTI™.
• Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), oo ay ku jiraan falcelinta dilaaga ah iyo kuwa nafta halis galinaya,
ku dhacay bukaanada ka dib daawaynta CARVYKTI™. HLH/MAS waxay ku dhici kartaa CRS ama sunta neerfaha.
• Cytopenia oo soo noqnoqda iyo/ama soo noqnoqda oo leh dhiig-bax iyo caabuq iyo baahi loogu talagalay tallaalka unugyada asliga ah ee hematopoietic
soo kabashadu waxay dhacday ka dib daawaynta CARVYKTI™.
• CARVYKTI™ waxa lagu heli karaa oo keliya barnaamijka xaddidan ee hoos yimaada Qiimaynta Khatarta iyo Xeeladda Yaraynta (REMS) ee loo yaqaan CARVYKTI ™ REMS Program.
DIGNIINTA IYO KA HORTAGA
Cytokine Release Syndrome (CRS) oo ay ku jiraan falcelinno dilaa ah ama nafta halis gelinaya, ayaa dhacay ka dib daawaynta CARVYKTI™ ee 95% (92/97) bukaanada helaya ciltacabtagene autoleucel. Fasalka 3 ama ka sareeya CRS (2019 ASTCT)1 ayaa ku dhacay 5% (5/97) bukaanada, iyadoo darajada 5 CRS laga soo sheegay 1 bukaan. Waqtiga dhexe ee bilawga CRS wuxuu ahaa 7 maalmood (kala duwan: 1-12 maalmood). Calaamadaha ugu caansan ee CRS waxaa ka mid ah pyrexia (100%), hypotension (43%), kororka aminotransferase aspartate (AST) (22%), qarqaryo (15%), aminotransferase alanine oo kordhay (14%) iyo sinus tachycardia (11%) . Fasalka 3 ama dhacdooyinka ka sarreeya ee la xidhiidha CRS waxaa ka mid ah AST iyo ALT oo kordhay, hyperbilirubinemia, hypotension, pyrexia, hypoxia, neefsashada oo xumaada, dhaawac kelyo ah oo faafa, xididdada xididdada dhiigga.
xinjirowga dhiigga, HLH/MAS, angina pectoris, tachycardia supraventricular iyo ventricular, xaalad la'aan, myalgias, kororka borotiinka C-reactive, ferritin, fosfatase dhiigga alkaline iyo gamma-glutamyl transferase.
Aqoonso CRS iyada oo ku saleysan bandhigga bukaan-socodka. Qiimee oo daaweeya sababaha kale ee qandho, hypoxia, iyo hypotension. CRS ayaa lagu soo warramey in ay la xiriirto natiijooyinka HLH/MAS, iyo physiology of syndromes-ka ayaa laga yaabaa in ay isdhaafsadaan. HLH/MAS waa khatar nafta halis gelin karta
xaalad. Bukaannada leh calaamadaha horumarka ee CRS ama CRS-da refractory inkastoo daawaynta, qiimee caddaynta HLH/MAS. Lixdan iyo sagaal ka mid ah 97 (71%) bukaanada ayaa helay tocilizumab iyo/ama corticosteroid ee CRS ka dib faleebo ciltacabtagene autoleucel. Afartan iyo afar
(45%) bukaanadu waxay heleen kaliya tocilizumab, kuwaas oo 33 (34%) ay heleen hal qiyaas iyo 11 (11%) waxay heleen wax ka badan hal qiyaas; 24 bukaan (25%) ayaa helay tocilizumab iyo corticosteroid, iyo hal bukaan (1%) ayaa helay kaliya corticosteroids. Hubi in ugu yaraan laba qiyaasood oo tocilizumab ah la heli karo ka hor faleebada CARVYKTI™.
La soco bukaanada ugu yaraan maalin kasta 10 maalmood ka dib faleebo CARVYKTI ™ ee xarun daryeel caafimaad oo ay shahaado ka dhigtay REMS calaamadaha iyo calaamadaha CRS. La soco bukaanka calaamadaha ama calaamadaha CRS ugu yaraan 4 toddobaad ka dib faleebo. Calaamadda ugu horreysa ee CRS, isla markiiba u bixi daawaynta daryeelka taageerada, tocilizumab, ama tocilizumab iyo corticosteroids. La tali bukaanada inay raadsadaan daryeel caafimaad oo degdeg ah haddii calaamadaha ama calaamadaha CRS ay dhacaan wakhti kasta. Sunta neerfaha, oo laga yaabo inay noqoto mid daran, nafta halis gelisa ama dhimasho, ayaa dhacday ka dib daawaynta CARVYKTI™. Sunta neerfaha waxaa ka mid ah ICANS, sunta neerfaha oo leh calamadaha iyo calaamadaha Parkinsonism, Guillain-Barré Syndrome, neerfaha durugsan, iyo curyaannada neerfaha cranial. Kala tali bukaanka calaamadaha iyo calaamadaha suntan neerfaha, iyo dabeecadda daahitaanka ee bilawga
qaar ka mid ah suntan. Far bukaannada inay raadsadaan daryeel caafimaad degdeg ah si loo qiimeeyo iyo maarayn dheeraad ah haddii calaamadaha ama calaamadaha mid ka mid ah sunta neerfaha ay dhacaan wakhti kasta.
Guud ahaan, hal ama dhowr nooc oo hoosaadyada sunta neerfaha ee hoos lagu sharraxay ayaa dhacay ka dib ciltacabtagene autoleucel ee 26% (25/97) bukaannada, kuwaas oo 11% (11/97) bukaannada ay la kulmeen Fasalka 3 ama dhacdooyin ka sarreeya. Noocyadan hoose ee sunta neerfaha ayaa sidoo kale lagu arkay laba daraasadood oo socda.
ICANS waxay ku dhacday 23% (22/97) bukaanada helaya ciltacabtagene autoleucel oo ay ku jiraan Fasalka 3 ama 4 dhacdooyinka 3% (3/97) iyo Fasalka 5 (dhimasho) 2% (2/97). Waqtiga dhexdhexaadka ah ee bilawga ICANS wuxuu ahaa 8 maalmood (qiyaastii 1-28 maalmood). Dhammaan 22 bukaan ee qaba ICANS waxay qabeen CRS. Muujinta ugu badan (≥5%) ee ICANS waxaa ka mid ah xanuunka maskaxda
(23%), aphasia (8%) iyo madax xanuun (6%). La soco bukaanka ugu yaraan maalin kasta 10 maalmood ka dib faleebo CARVYKTI ™ ee xarunta daryeelka caafimaadka ee REMS-shahay ee calaamadaha iyo calaamadaha ICANS. Meesha ka saar sababaha kale ee calaamadaha ICANS. La soco bukaanada calaamadaha ama calaamadaha ICANS ugu yaraan 4 usbuuc ka dib faleebo oo si degdeg ah u daaw. Sunta neerfaha waa in lagu maareeyaa daryeel taageero ah iyo/ama corticosteroids haddii loo baahdo.
Parkinsonism: Bukaannada 25 ee cilmi-baarista CARTITUDE-1 ee la kulma neurotoxicity, shan bukaan oo lab ah ayaa lahaa sunta neerfaha oo leh calaamado iyo calaamado dhowr ah oo Parkinsonism ah, oo ka duwan habka difaaca jirka ee unugyada neurotoxicity syndrome (ICANS). Neerfaha
sunta leh Parkinsonism ayaa lagu soo warramey tijaabooyinka kale ee socda ee ciltacabtagene autoleucel. Bukaanadu waxay lahaayeen calaamadaha Parkinsonian iyo nonparkinsonian oo ay ku jiraan gariir, bradykinesia, dhaqdhaqaaq aan ikhtiyaari ahayn, stereotypy, luminta dhaq-dhaqaaqa kediska ah, wejiyada daboolan, dareen la'aan, saameyn siman, daal, qallafsanaan, dib u dhac maskaxeed, micrographia, dysgraphia, apraxia, caajisnimo, wareer, somnole
miyir beelid, falcelis daahsan, hyperreflexia, xusuusta oo luma, liqitaanka oo adkaata, saxaro la'aanta, hoos u dhaca, joogsiga istaaga, socodka socodka, daciifnimada murqaha iyo luminta, dhaqdhaqaaqa dhaqdhaqaaqa, dhaqdhaqaaqa iyo dareenka luminta, mutism akinetic, iyo calamadaha sii daaya laf dhabarta.
Dhexdhexaadinta bilawga parkinsonism-ka ee bukaannada 5 ee ku jira CARTITUDE-1 waxay ahayd 43 maalmood (qiyaastii 15-108) laga soo bilaabo faleebo ciltacabtagene autoleucel.
La soco bukaanada calaamadaha iyo calaamadaha Parkinsonism ee laga yaabo in ay daahiyaan bilawga oo lagu maareeyo tallaabooyin daryeel taageero ah.
Waxaa jira macluumaad xaddidan oo waxtar leh oo leh dawooyinka loo isticmaalo daaweynta cudurka Parkinson, hagaajinta ama xallinta
calaamadaha Parkinsonism ka dib daaweynta CARVYKTI™.
Guillain-Barré Syndrome: Natiijo dilaa ah oo daba socota Guillain-Barré Syndrome (GBS) ayaa ku dhacday daraasad kale oo socota
ciltacabtagene autoleucel inkasta oo lagu daaweeyay immunoglobulins xididada. Calaamadaha la soo sheegay waxaa ka mid ah kuwa waafaqsan kala duwanaanshaha MillerFisher ee GBS, maskaxda, daciifnimada dhaqdhaqaaqa, qaska hadalka iyo polyradiculoneuritis.
La soco GBS Qiimee bukaanada soo bandhigaya neuropathy durugsan ee GBS. Tixgeli daaweynta GBS oo leh cabbiro daryeel taageero iyo iyadoo lala kaashanayo immunoglobulins iyo beddelka balaasmaha, iyadoo ku xiran darnaanta GBS.
Peripheral Neuropathy: Lix bukaan oo ku jira CARTITUDE-1 ayaa sameeyay neuropathy peripheral. Neuropathy-yadan ayaa loo soo bandhigay sida dareenka, mootada ama dareemayaasha dareemayaasha. Waqtiga dhexdhexaadka ah ee bilawga calaamaduhu wuxuu ahaa 62 maalmood (qiyaastii 4-136 maalmood), muddada dhexdhexaadka ah ee neuropathy durugsan waxay ahayd 256 maalmood (qiyaastii 2-465 maalmood) oo ay ku jiraan kuwa qaba neuropathy socda. Bukaanada la kulmey neuropathy durugsan waxay sidoo kale la kulmeen curyaan neerfaha cranial ama GBS tijaabooyin kale oo socda ee ciltacabtagene autoleucel.
Cranial Neve Palsies: Saddex bukaan (3.1%) waxay la kulmeen curyaan neerfaha cranial ee CARTITUDE-1. Dhammaan saddexda bukaan waxay lahaayeen dareemaha 7aad ee cranial
curyaan; Hal bukaan ayaa sidoo kale lahaa 5aad neerfaha dareemaha ee cranial. Waqtiga dhexdhexaadka ah ee bilawga ah wuxuu ahaa 26 maalmood (qiyaastii 21-101 maalmood) ka dib faleebo
ciltacabtagene autoleucel. Dhacdooyinka 3aad iyo 6aad ee curyaanka neerfaha cranial, laba-geesoodka 7th ee curyaanka neerfaha, ka sii daraya curyaanka neerfaha cranial ka dib hagaajinta, iyo dhacdooyinka neuropathy peripheral neuropathy ee bukaanka qaba curyaan neerfaha cranial ayaa sidoo kale lagu soo warramey tijaabooyin socda
ee ciltacabtagene autoleucel. Kala soco bukaanka calaamadaha iyo calaamadaha curyaannada neerfaha cranial. Tixgeli maaraynta corticosteroids habaysan, taas oo ku xidhan darnaanta iyo horumarka calaamadaha iyo calaamadaha. Hemophagocytic Lymphohistiocytosis (HLH)/Makrophage Activation Syndrome (MAS: Fatal HLH waxay ku dhacday hal bukaan (1%), 99
maalmo kadib ciltacabtagene autoleucel. Dhacdada HLH waxaa ka horreeyay CRS oo soconaysa 97 maalmood. Muujinta HLH/MAS
waxaa ka mid ah hypotension, hypoxia oo leh burburka alveolar fidsan, coagulopathy, cytopenia, iyo hawlgabka xubnaha badan, oo ay ku jiraan shaqada kelyaha. HLH waa xaalad nafta halis gelisa oo leh heer dhimasho oo sarreeya haddii aan la aqoonsan oo aan goor hore la daweyn. Daaweynta HLH/MAS waa in lagu maamulaa halbeegyada hay'adaha. CARVYKTI ™ REMS: Sababtoo ah khatarta CRS iyo sunta neerfaha, CARVYKTI™ waxaa lagu heli karaa oo keliya iyada oo loo marayo barnaamijka xaddidan ee hoos yimaada Istaraatiijiyada Qiimaynta iyo Khatarta (REMS) ee loo yaqaan CARVYKTI™ REMS.
Macluumaad dheeraad ah ayaa laga heli karaa www.CARVYKTIrems.com ama 1-844-672-0067.
Prolonged and Recurrent Cytopenias: Patients may exhibit prolonged and recurrent cytopenias following lymphodepleting chemotherapy and CARVYKTI™ infusion. One patient underwent autologous stem cell therapy for hematopoietic reconstitution due to prolonged thrombocytopenia.
CARTITUDE-1, 30% (29/97) bukaanada waxay la kulmeen Fasalka 3 ama 4 neutropenia oo daba dheeraaday iyo 41% (40/97) bukaanada waxay la kulmeen Fasalka 3 ama 4 thrombocytopenia oo daba dheeraaday oo aan la xalin maalinta 30 ka dib faleebo cittacabtagene autoleucel.
Fasalka 3 ama 4 ee soo noqnoqda neutropenia, thrombocytopenia, lymphopenia iyo dhiig-yaraan ayaa lagu arkay 63% (61/97), 18% (17/97), 60% (58/97),
iyo 37% (36/97) ka dib markii laga soo kabsado fasalka 3 ama 4 cytopenia ka dib faleebo. Ka dib Maalinta 60 ee ku xigta ciltacabtagene autoleucel
faleebo, 31%, 12% iyo 6% bukaanada ayaa ku soo noqnoqday Fasalka 3 ama ka sareeya lymphopenia, neutropenia iyo thrombocytopenia, siday u kala horreeyaan, ka dib markii ay ka soo kabsadeen Fasalka 3 ama 4 cytopenia. Boqolkiiba 84 (97/XNUMX) bukaanada ayaa lahaa hal, laba, ama saddex ama ka badan
soo noqnoqoshada Fasalka 3 ama 4 cytopenia ka dib soo kabashada bilowga ah ee Fasalka 3 ama 4 cytopenia. Lix iyo 11 bukaan waxay qabeen Fasalka 3 ama 4 neutropenia iyo thrombocytopenia, siday u kala horreeyaan, wakhtiga dhimashada.
La soco tirooyinka dhiiga ka hor iyo ka dib faleebada CARVYKTI™. Maamul cytopeniyas leh arrimo koritaan iyo taageerada ku shubista wax soo saarka dhiigga sida waafaqsan tilmaamaha hay'adaha maxalliga ah.
Caabuqyada: CARVYKTI™ waa in aan la siin bukaanka qaba caabuq firfircoon ama xanuunada bararka. Infekshanno daran, nafta halis gelinaya ama dilaa ah ayaa ku dhacay bukaannada ka dib faleebo CARVYKTI™ ah.
Caabuqa (dhammaan darajooyinka) ayaa ku dhacay 57 (59%) bukaan. Fasalka 3 ama 4 caabuqa ayaa ku dhacay 23% (22/97) bukaanada; Fasalka 3 ama 4 infekshannada cudur-sidaha aan la cayimin ayaa ku dhacay 17%, caabuqyada fayraska ee 7%, caabuqyada bakteeriyada 1%, iyo caabuqyada fungal ee 1% bukaannada.
Guud ahaan, afar bukaan ayaa qabay caabuqyada Fasalka 5: sambabada sambabada (n=1), sepsis (n=2) iyo sambabada (n=1).
La soco bukaanka calaamadaha iyo calaamadaha caabuqa ka hor iyo ka dib faleebada CARVYKTI oo dawee bukaanka si habboon. Maamul ka hortag, ka-hortag iyo/ama ka-hortagga-ka-hortagga-ka-hortagga ee ku-daweynta sida waafaqsan hab-raacyada hay'adaha caadiga ah. Febrile neutropenia waxay ahayd
observed in 10% of patients after ciltacabtagene autoleucel infusion, and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids and other supportive care, as medically indicated.
Dib-u-kicinta Fayraska: Fayraska cagaarshow B (HBV) dib-u-kicinta, xaaladaha qaarkood oo keena cagaarshow buuxa, beer-xumo iyo dhimasho, waxay ku dhici kartaa bukaannada qaba hypogammaglobulinemia. Samee baaritaanka Cytomegalovirus (CMV), HBV, fayraska cagaarshow C (HCV), iyo fayraska difaaca jirka (HIV), ama wax kasta oo kale oo cudur ah haddii kiliinikada lagu tilmaamo si waafaqsan tilmaamaha kiliinikada ka hor inta aan la ururin unugyada wax soo saarka. Tixgeli daawaynta ka hortagga fayraska si looga hortago dib-u-kicinta fayraska marka loo eego tilmaamaha hay'adaha maxalliga ah/dhaqanka caafimaad.
Hypogammaglobulinemia waxaa lagu soo warramey inay tahay dhacdo xun 12% (12/97) bukaanada; Heerarka shaybaarka IgG ayaa hoos uga dhacay 500 mg/dL ka dib faleebo 92% (89/97) bukaannada. La soco heerarka immunoglobulin ka dib daawaynta CARVYKTI™ oo maamul IVIG ee IgG
<400 mg/dL Maamul habraacyada hay'adaha maxalliga ah, oo ay ku jiraan taxaddarrada caabuqa iyo antibiyootiga ama ka hortagga fayraska.
Isticmaalka Tallaalka Nool: Badbaadada tallaalka fayraska nool ee tallaalada fayraska inta lagu jiro ama daba-galka daawaynta CARVYKTI™ lama darsin.
Tallaalka fayraska nool laguma talinayo ugu yaraan 6 toddobaad ka hor bilowga daaweynta kemotherabi ee lymphodepleting, inta lagu jiro daawaynta CARVYKTI™, iyo ilaa uu ka soo kabsado difaaca ka dib daawaynta CARVYKTI™.
Dareen-celinta xasaasiyadda ayaa ku dhacay 5% (5/97) bukaannada ka dib faleebo ciltacabtagene autoleucel. Dareen-celin xasaasiyadeed oo daran, oo ay ku jirto anaphylaxis, waxaa laga yaabaa inay sabab u tahay dimethyl sulfoxide (DMSO) ee ku jirta CARVYKTI™. Bukaanka waa in si taxadar leh loola socdo 2 saacadood ka dib faleebo si loo ogaado calaamadaha iyo calaamadaha falcelinta daran. Si degdeg ah u daawee oo si habboon u maareey iyadoo loo eegayo darnaanta falcelinta xasaasiyadda.
Xannaanada Labaad: Bukaan-socodka waxaa laga yaabaa in ay yeeshaan malignancies labaad. La soco nolosha-dheer cudurada malignantiga ah. Haddii ay dhacdo in xumaanta labaad ay dhacdo, kala xidhiidh Janssen Biotech, Inc., 1-800-526-7736 si aad u warbixiso iyo si aad u hesho tilmaamo ku saabsan ururinta
muunado bukaan oo lagu tijaabiyo malignant-ka labaad ee asalka unugga T.
Saamaynta Awoodda Wadista iyo Isticmaalka Mashiinnada: Sababtoo ah suurtagalnimada dhacdooyinka neerfayaasha, oo ay ku jiraan xaalad maskaxeed oo isbeddelay, suuxdin, hoos u dhaca neurocognitive, ama neuropathy, bukaanku waxay halis ugu jiraan isbeddelka ama hoos u dhaca miyir-qabka ama isuduwidda toddobaadyada 8 ee soo socda
Faleebo CARVYKTI. Kula tali bukaanada inay ka waantoobaan wadista oo ay ku lug yeeshaan shaqooyinka khatarta ah ama hawlaha, sida ku shaqaynta mishiinada culus ama khatarta ah muddadan bilowga ah, iyo haddii ay dhacdo bilawga cusub ee sunta neerfaha.
LACAG LA'AAN AH
Dareen-celinta xun ee ugu badan ee aan shaybaarka ahayn (dhacdooyinka ka badan 20%) waa pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, murqo xanuun, daal, caabuqa pathogene aan la cayimin, qufac, qarqaryo, shuban, lallabbo, maskaxda, hoos u dhaca rabitaanka cuntada, sare. caabuqa neef-mareenka, madax-xanuun, tachycardia, dawakhaad, dyspnea, barar, caabuq fayras ah, xinjirowga dhiigga, calool-istaagga, iyo matag. Dareen-celinta xun ee shaybaadhka ugu caansan (dhacdooyinka ka weyn ama la mid ah 50%) waxaa ka mid ah thrombocytopenia, neutropenia, dhiig-yaraan, sare u qaadida aminotransferase, iyo hypoalbuminemia.
Fadlan akhri Xogta Qorista oo buuxda oo ay ku jiraan Digniinta Sanduuqa ee CARVYKTI™.
