March 2022: Ngokusho kukaJohnson & Johnson, indlela yokwelapha eyakhiwe yile nkampani nozakwethu ozinze eChina Inkampani Legend Biotech Corp ukwelapha uhlobo lomdlavuza wamangqamuzana amhlophe egazi kuvunywe yi-US Food and Drug Administration.
Isinqumo se-FDA sivula indlela yokuthi umkhiqizo wokuqala kaLegend ugunyazwe e-United States, esikhathini lapho le nhlangano inyuse ukucutshungulwa kokuhlolwa kwemithi okwenziwa eChina. Ukwelashwa kwe-Legend-J&J kwazanywa okokuqala e-China, kwase kuba e-United States nase-Japan.
Impatho, I-Carvykti/Cilta-cel, ingeyeqembu lezidakamizwa elaziwa ngokuthi yi-CAR-T Therapies, noma 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.
I-Legend ne-J&J izothengisa umuthi e-Greater China ngo-70-30 ukuhlukaniswa ngenzuzo, futhi kuwo wonke amanye amazwe ekuhlukaniseni kuka-50-50 enzuzweni.
February 28, 2022-I-Legend Biotech Corporation (NASDAQ: LEGN) (I-Legend Biotech), inkampani yomhlaba wonke ye-biotechnology ethuthukisa, ekhiqiza futhi ethengisa izindlela zokwelapha ezintsha zokwelapha izifo ezisongela ukuphila, namuhla imemezele ukuthi i-US Food and Drug Administration (FDA) igunyaze umkhiqizo wayo wokuqala, i-CARVYKTI™(ciltacabtagene autoleucel; ciltacel), ukuze zelashwe abantu abadala abane-myeloma eminingi ebuyele emuva noma ephikisayo (RRMM) abaye bathola imigqa yokwelapha emine noma ngaphezulu yangaphambili, okuhlanganisa i-proteasome inhibitor, i-immunomodulatory agent, kanye ne-anti-CD38 monoclonal antibody. I-Legend Biotech ingene esivumelwaneni selayisense yomhlaba wonke kanye nesivumelwano sokusebenzisana ne-Janssen Biotech, Inc. (Janssen) sokuthuthukisa nokudayisa i-ciltacel ngoZibandlela wezi-2017.
I-CARVYKTITM iyi-chimeric antigen receptor T-cell (CAR-T) yokwelapha ene-B-cell maturation antigen (BCMA)-embili eqondise isizinda esisodwa.
amasosha omzimba futhi anikezwe njengomuthi wesikhathi esisodwa ngebanga lethamo elinconyiwe elingu-0.5 kuya ku-1.0 x 106 amaseli T asebenzayo e-CAR-positive ngekhilogramu ngayinye yesisindo somzimba. Ocwaningweni olubalulekile lwe-CARTITUDE-1, izimpendulo ezijulile neziqinile zibonwe ezigulini ezine-RRMM (n=97), ezinesilinganiso sokuphendula esiphezulu (ORR) samaphesenti angama-98 (isikhathi sokuzethemba esingamaphesenti angama-95 [CI]: 92.7-99.7) okuhlanganisa Amaphesenti angama-78 eziguli ezithola ukuqina
impendulo ephelele (sCR, 95 amaphesenti CI: 68.8-86.1).
I-1 Ekulandeleni kwezinyanga ezingu-18 ezimaphakathi, ubude besikhathi sokuphendula (DOR) kwakuyizinyanga ezingu-21.8 (amaphesenti angu-95 CI 21.8-awanakulinganiswa).
1
I-CARVYKTI™ itholakala kuphela ngohlelo olukhawulelwe ngaphansi kwe-Risk Evaluation and Mitigation Strategy (REMS) ebizwa ngokuthi i-CARVYKTI™.
Uhlelo lwe-REMS.1 Ulwazi Lokuphepha lwe-CARVYKTI™ luhlanganisa Isexwayiso Esinebhokisi mayelana ne-Cytokine Release Syndrome (CRS), Immune
I-Effector Cell-Associated Neurotoxicity Syndrome (ICANS), Parkinsonism kanye ne-Guillain-Barré syndrome, i-hemophagocytic
i-lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), kanye ne-cytopenia ende kanye/noma ephindaphindayo.
1 Izexwayiso kanye nezinyathelo zokuqapha
zihlanganisa i-cytopenias ende futhi ephindaphindayo, izifo, i-hypogammaglobulinemia, ukusabela kwe-hypersensitivity, izifo zesibili kanye
imiphumela ekhonweni lokushayela nokusebenzisa imishini.
1 Ukusabela okungekuhle okuvame kakhulu (≥20 amaphesenti) yi-pyrexia, CRS,
i-hypogammaglobulinemia, i-hypotension, ubuhlungu bemisipha namathambo, ukukhathala, izifo-i-pathogen engashiwongo, ukukhwehlela, ukugodola, isifo sohudo, isicanucanu, i-encephalopathy, ukuncipha kwesifiso sokudla, ukutheleleka komgudu wokuphefumula ongenhla, ikhanda elibuhlungu, i-tachycardia, isiyezi, i-dyspnea, i-edema, izifo ezibangelwa amagciwane, ukuqunjelwa, i-coagulopathy, ukuhlanza.
"I-Multiple myeloma isalokhu iyisifo esingelapheki esineziguli ezelashwe kakhulu ezibhekene nezibikezelo ezimbi ezinezinketho zokwelashwa ezilinganiselwe," kusho u-Ying Huang, PhD, i-CEO kanye ne-CFO ye-Legend Biotech. “Ukugunyazwa kwanamuhla kwe-CARVYKTI yisikhathi esibalulekile ku-Legend Biotech ngoba kunjalo
ukugunyazwa kwethu kokumaketha okokuqala ngqa, kodwa okusijabulisa kakhulu amandla omuthi ukuthi abe inketho yokwelapha enomthelela ezigulini ezidinga izikhawu ezinde, ezingenakwelashwa. Lena eyokuqala kwemithi eminingi yokwelapha amangqamuzana esihlela ukuyiletha ezigulini njengoba siqhubeka nokuthuthukisa ipayipi lethu kuzo zonke izifunda zezifo.”
I-Myeloma eminingi ithinta uhlobo lwamangqamuzana amhlophe egazi abizwa ngokuthi ama-plasma cell, atholakala emnkantsheni wamathambo.2 Iningi leziguli
ukubuyela emuva ngemva kokwelashwa kokuqala futhi ubhekane nokubikezela okubi ngemva kokwelashwa ngamakilasi amathathu ezidakamizwa ezinkulu, okuhlanganisa
i-immunomodulatory agent, i-proteasome inhibitor kanye ne-anti-CD38 monoclonal antibody.3,4,5
"Uhambo lokwelapha lweningi leziguli eziphila ne-myeloma eminingi luwumjikelezo ongapheli wokuxolelwa nokubuyela emuva ngeziguli ezimbalwa ezithola impendulo ejulile njengoba zithuthuka emigqeni yokwelapha kamuva," kusho uDkt. Sundar Jagannath, MBBS, uProfesa Wezokwelapha. I-Hematology ne-Medical Oncology eNtabeni iSinayi, kanye nomphenyi wesifundo oyinhloko. “Yingakho ngijabule kakhulu ngemiphumela yocwaningo lwe-CARTITUDE-1, olukhombise ukuthi i-cilta-cel inganikeza izimpendulo ezijulile neziqinile kanye nesikhathi eside.
izikhawu ezingalashwa, nakulesi sibalo seziguli ezine-myeloma eshaywe kakhulu. Ukugunyazwa kwanamuhla kwe-CARVYKTI kusiza ekubhekaneni nesidingo esikhulu esingafinyeleleki salezi ziguli.”
Njengomuthi oqondene nawe, ukuphatha kwe-CARVYKTI™ kudinga ukuqeqeshwa okubanzi, ukulungiswa, kanye nesitifiketi ukuze kuqinisekiswe ukuzizwisa kweziguli ezingenazihibe. Ngokusebenzisa indlela yezigaba, u-Legend no-Janssen bazovula inethiwekhi elinganiselwe yezikhungo zokwelapha eziqinisekisiwe njenge
basebenzela ukukala umthamo wokukhiqiza futhi bakhulise ukutholakala kwe-CARVYKTI™ kulo lonke elase-US ngo-2022 nangale kwalokho, baqinisekisa ukuthi ukwelashwa kwe-CARVYKTI™ kunganikezwa odokotela be-oncologists kanye neziguli zabo ngendlela ethembekile nefika ngesikhathi.
Mayelana ne-CARVYKTI™ (Ciltacabtagene autoleucel; cilta-cel) I-CARVYKTI™ iqondiswa yi-BCMA, i-autologous T-cell immunotherapy eqondiswe ngofuzo, ehilela ukuhlela kabusha amaseli e-T esiguli nge-transgene encoding i-chimeric antigen receptor (CAR) ekhomba futhi iqede. amaseli aveza i-BCMA. I-BCMA ivezwa ngokuyinhloko phezu kwamaseli e-myeloma B-lineage amaningi ayingozi, kanye namaseli e-B asekupheleni kwesiteji namaseli e-plasma. Iphrotheni ye-CARVYKTI™ CAR ihlanganisa amasosha omzimba amabili esizinda esisodwa aqondiswe ku-BCMA aklanyelwe ukunikeza ukukhuthala okuphezulu ngokumelene ne-BCMA yomuntu. Phezu kokubopha ku
I-BCMA-eveza amaseli, i-CAR ikhuthaza ukusebenza kwe-T-cell, ukunwetshwa, nokuqedwa kwamaseli okuhlosiwe.
NgoZibandlela wezi-2017, i-Legend Biotech Corporation yangena esivumelwaneni selayisense yomhlaba wonke kanye nesivumelwano sokusebenzisana ne-Janssen Biotech, Inc. sokuthuthukisa nokudayisa i-cilta-cel.
Ngo-Ephreli 2021, uLegend wamemezela ukuthunyelwa Kwesicelo Sokugunyaza Ukumaketha ku-European Medicines Agency efuna imvume ye-cilta-cel yokwelapha iziguli ezine-myeloma eminingi ebuyele emuva kanye/noma ephikayo. Ngaphezu kwe-US Breakthrough Therapy Designation eyanikezwa ngoDisemba 2019, i-cilta-cel ithole i-Breakthrough Therapy Designation e-China ngo-Agasti 2020. U-Cilta-cel uphinde wathola i-Orphan Drug Designation evela ku-US FDA ngoFebhuwari 2019, kanye nakuKhomishini YaseYurophu ngoFebhuwari 2020. .
Mayelana Nocwaningo Lwe-CARTITUDE-1
I-CARTITUDE-1 (NCT03548207) iyisigaba 1b/2 esiqhubekayo, ilebula evulekile, ingalo eyodwa, isilingo esimaphakathi esihlola i-cilta-cel yokwelashwa kweziguli ezikhulile ezine-myeloma eminingi ebuyele emuva noma ephikisayo, eyake yathola okungenani imigqa emithathu yangaphambilini. yokwelapha okuhlanganisa i-proteasome inhibitor (PI), i-immunomodulatory agent (IMiD) kanye ne-anti-CD38 monoclonal antibody. Ezigulini ezingama-97 ezibhalisele
ocwaningweni, amaphesenti angama-99 ayephikisana nomugqa wokugcina wokwelashwa kanti amaphesenti angama-88 ayengama-triple-class refractory, okusho ukuthi umdlavuza wabo awuzange uphendule, noma awusaphenduli, ku-IMiD, i-PI kanye ne-anti-CD38 monoclonal antibody.1
Ukusebenza kwesikhathi eside kanye nephrofayili yokuphepha ye-cilta-cel iyahlolwa ocwaningweni oluqhubekayo lwe-CARTITUDE-1, ngemiphumela yokulandelela yeminyaka emibili esanda kwethulwa ku-ASH 2021.6
Mayelana ne-Myeloma eminingi
I-Multiple myeloma umdlavuza wegazi ongelapheki oqala emnkantsheni futhi ubonakala ngokwanda ngokweqile kwamaseli e-plasma.
Ngo-2022, kulinganiselwa ukuthi bangaphezu kuka-34,000 abantu abazotholakala bene-myeloma eminingi, futhi abantu abangaphezu kwe-12,000 bazotholakala.
babulawa yilesi sifo e-US
7 Nakuba ezinye iziguli ezine-myeloma eminingi zingenazo nhlobo izimpawu, iziguli eziningi zixilongwa ngenxa
izimpawu ezingase zihlanganise izinkinga zamathambo, ukuncipha kwegazi, ukuphakama kwe-calcium, izinkinga zezinso noma izifo.
8 Nakuba ukwelashwa kungase
umphumela wokuxolelwa, ngeshwa, iziguli cishe zizophinde zibuye.
3 Iziguli ezibuyela ekuguleni ngemva kokwelashwa ngamakhambi ajwayelekile, okuhlanganisa ama-protease inhibitors, ama-immunomodulatory agents, kanye ne-anti-CD38 monoclonal antibody, zinezibikezelo ezimbi kanye nezinketho zokwelapha ezimbalwa ezitholakalayo.
I-CARVYKTI™ Ulwazi Olubalulekile Lokuphepha IZIKHOMBISA NOKUSETSHENZISWA
I-CARVYKTI™ (ciltacabtagene autoleucel) iyi-B-cell maturation antigen (BCMA)-eqondiswe ngofuzo ye-autologous T cell immunotherapy ekhonjiswe ukwelashwa kweziguli ezikhulile ezine-myeloma eminingi ebuyele emuva noma ephikisayo, ngemva kwemigqa yokwelapha emine noma ngaphezulu yangaphambili, okuhlanganisa i-proteasome. inhibitor, i-immunomodulatory agent, kanye ne-anti-CD38 monoclonal antibody.
ISEXWAYISO: I-CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, NOKWINDLELA KANYE KANYE KANYE
I-CYTOPENIA
• I-Cytokine Release Syndrome (CRS), okuhlanganisa ukusabela okubulalayo noma okusongela ukuphila, kwenzeka ezigulini ezilandela ukwelashwa
I-CARYKTI™. Unganikezi i-CARVYKTI™ ezigulini ezinokutheleleka okusebenzayo noma ukuphazamiseka kokuvuvukala. Yelapha i-CRS enzima noma esongela ukuphila nge-tocilizumab noma i-tocilizumab ne-corticosteroids.
• I-Immune Effective Cell-Associated Neurotoxicity Syndrome (ICANS), engase ibulale noma ibeke ukuphila engozini, yenzeka ngokulandelayo.
Ukwelashwa nge-CARVYKTI™, okuhlanganisa ngaphambi kokuqala kwe-CRS, kanyekanye ne-CRS, ngemva kokulungiswa kwe-CRS, noma uma ingekho i-CRS. Gada imicimbi ye-neurologic ngemva kokwelashwa nge-CARVYKTI™. Nikeza ukunakekelwa okusekelayo kanye/noma i-corticosteroids njengoba kudingeka.
• I-Parkinsonism kanye ne-Guillain-Barré syndrome kanye nezinkinga ezihambisana nazo eziholela ekufeni noma ukusabela okusongela ukuphila
kwenzeke ngemva kokwelashwa nge-CARVYKTI™.
• I-Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), okuhlanganisa ukusabela okubulalayo nokusongela ukuphila,
kwenzeka ezigulini ezilandela ukwelashwa nge-CARVYKTI™. I-HLH/MAS ingenzeka nge-CRS noma ubuthi be-neurologic.
• I-cytopenias ehlala isikhathi eside kanye/noma ephindaphindayo yokopha kanye nokutheleleka kanye nesidingo sokufakelwa kwe-stem cell for hematopoietic
ukululama kwenzeke ngemva kokwelashwa nge-CARVYKTI™.
• I-CARVYKTI™ itholakala kuphela ngohlelo olukhawulelwe ngaphansi Kwesu Lokuhlola Ubungozi kanye Nesu Lokunciphisa (REMS) elibizwa ngokuthi Uhlelo lwe-CARVYKTI™ REMS.
IZIXWAYISO NEZINYATHELO
I-Cytokine Release Syndrome (CRS) ehlanganisa ukusabela okubulalayo noma okusongela ukuphila, kwenzeka ngemva kokwelashwa nge-CARVYKTI™ ku-95% (92/97) weziguli ezithola i-ciltacabtagene autoleucel. I-CRS yeBanga lesi-3 noma ngaphezulu (ibanga le-ASTCT lika-2019) 1 yenzeke ku-5% (5/97) weziguli, kanti iBanga lesi-5 le-CRS libikwe esigulini esisodwa. Isikhathi esimaphakathi sokuqala kwe-CRS kwakuyizinsuku eziyi-1 (ububanzi: izinsuku ezi-7-1). Ukubonakaliswa okuvame kakhulu kwe-CRS kuhlanganisa i-pyrexia (12%), hypotension (100%), ukwanda kwe-aspartate aminotransferase (AST) (43%), ukugodola (22%), ukwanda kwe-alanine aminotransferase (15%) kanye ne-sinus tachycardia (14%). . Izehlakalo zeBanga lesi-11 noma eziphakeme ezihlotshaniswa ne-CRS zihlanganisa ukwanda kwe-AST ne-ALT, i-hyperbilirubinemia, i-hypotension, i-pyrexia, i-hypoxia, ukwehluleka ukuphefumula, ukulimala kwezinso okukhulu, ukusabalalisa kwe-intravascular
i-coagulation, i-HLH/MAS, i-angina pectoris, i-supraventricular ne-ventricular tachycardia, i-malaise, i-myalgias, ukwanda kwe-C-reactive protein, i-ferritin, i-alkaline phosphatase yegazi kanye ne-gamma-glutamyl transferase.
Khomba i-CRS ngokusekelwe ekwethulweni komtholampilo. Hlola futhi welaphe ezinye izimbangela zemfiva, i-hypoxia, ne-hypotension. I-CRS kubikwe ukuthi ihlotshaniswa nokutholwe yi-HLH/MAS, futhi i-physiology yama-syndromes ingase idlulelane. I-HLH/MAS iyingozi engozini
isimo. Ezigulini ezinezimpawu eziqhubekayo ze-CRS noma i-CRS ephikisayo naphezu kokwelashwa, hlolela ubufakazi be-HLH/MAS. Iziguli ezingamashumi ayisithupha nesishiyagalolunye kwezingu-97 (71%) zithole i-tocilizumab kanye/noma i-corticosteroid ye-CRS ngemva kokufakwa kwe-ciltacabtagene autoleucel. Amashumi amane nane
(45%) iziguli zithole i-tocilizumab kuphela, okungama-33 (34%) kuzo zathola umthamo owodwa kwathi eziyi-11 (11%) zathola umthamo ongaphezu kowodwa; Iziguli ezingama-24 (25%) zithole i-tocilizumab ne-corticosteroid, futhi isiguli esisodwa (1%) sathola kuphela i-corticosteroids. Qinisekisa ukuthi ubuncane bemithamo emibili ye-tocilizumab iyatholakala ngaphambi kokujova i-CARVYKTI™.
Gada iziguli okungenani nsuku zonke izinsuku eziyi-10 kulandela ukumnika i-CARVYKTI™ esikhungweni sezempilo esiqinisekiswe i-REMS ukuze uthole izimpawu nezimpawu ze-CRS. Gada iziguli ukuze uthole izimpawu noma izimpawu ze-CRS okungenani amaviki angu-4 ngemva kokumnika. Uma ubona uphawu lokuqala lwe-CRS, sungula ngokushesha ukwelashwa ngokunakekelwa okusekelayo, i-tocilizumab, noma i-tocilizumab ne-corticosteroids. Yeluleka iziguli ukuthi zifune usizo lwezokwelapha ngokushesha uma kwenzeka kuvela izimpawu noma izimpawu ze-CRS nganoma yisiphi isikhathi. Ubuthi be-neurologic, obungase bube nzima, busongela ukuphila noma bubulale, buvele ngemva kokwelashwa nge-CARVYKTI™. Ubuthi be-neurologic buhlanganisa i-ICANS, ubuthi be-neurologic obunezimpawu nezimpawu ze-parkinsonism, i-Guillain-Barré Syndrome, i-peripheral neuropathies, kanye ne-cranial nerve palsies. Yeluleka iziguli ngezimpawu nezimpawu zalobu buthi be-neurologic, kanye nesimo sokubambezeleka sokuqala
ezinye zalezi toxicities. Yala iziguli ukuthi zifune usizo lwezokwelapha ngokushesha ukuze zihlolwe futhi ziphathwe uma izimpawu noma izimpawu zanoma yibuphi lobu buthi be-neurologic zenzeka nganoma yisiphi isikhathi.
Sekukonke, i-subtype eyodwa noma ngaphezulu yobuthi be-neurologic echazwe ngezansi yenzeke ngokulandela i-ciltacabtagene autoleucel ku-26% (25/97) yeziguli, lapho u-11% (11/97) weziguli ahlangabezana neBanga lesi-3 noma izehlakalo eziphezulu. Lezi zinhlobo ezincane zobuthi be-neurologic nazo zabonwa ezifundweni ezimbili eziqhubekayo.
I-Immune Effect Cell-Associated Neurotoxicity Syndrome (ICANS): I-ICANS yenzeka ku-23% (22/97) yeziguli ezithola i-ciltacabtagene autoleucel okuhlanganisa imicimbi yeBanga lesi-3 noma lesi-4 ku-3% (3/97) kanye nezehlakalo zeBanga lesi-5 (ezibulalayo) ku-2%. (2/97). Isikhathi esimaphakathi sokuqala kwe-ICANS kwakuyizinsuku eziyi-8 (ububanzi bezinsuku ezi-1-28). Zonke iziguli ezingama-22 ezine-ICANS zine-CRS. Ukubonakaliswa okuvamile (≥5%) kwe-ICANS kufaka phakathi i-encephalopathy
(23%), aphasia (8%) kanye nekhanda elibuhlungu (6%). Gada iziguli okungenani nsuku zonke izinsuku eziyi-10 kulandela ukumnika i-CARVYKTI™ esikhungweni sezempilo esiqinisekiswe i-REMS ukuze uthole izimpawu nezimpawu ze-ICANS. Khipha ezinye izimbangela zezimpawu ze-ICANS. Gada iziguli ukuze uthole izimpawu noma izimpawu ze-ICANS okungenani amaviki angu-4 ngemva kokumnika futhi welaphe ngokushesha. Ubuthi be-neurologic kufanele buphathwe ngokunakekelwa okusekela kanye/noma i-corticosteroids njengoba kudingeka.
I-Parkinsonism: Ezigulini ezingama-25 ocwaningweni lwe-CARTITUDE-1 ezibhekana nanoma iyiphi i-neurotoxicity, iziguli ezinhlanu zesilisa zazinobuthi be-neurologic obunezimpawu nezimpawu ezimbalwa ze-parkinsonism, ezihlukile ku-immune effector cell-associated neurotoxicity syndrome (ICANS). I-Neurologic
ubuthi nge-parkinsonism kuye kwabikwa kwezinye izivivinyo eziqhubekayo ze-ciltacabtagene autoleucel. Iziguli zazinezimpawu ze-parkinsonian nezingezona ze-parkinsonian ezihlanganisa ukuthuthumela, i-bradykinesia, ukunyakaza okuzenzakalelayo, i-stereotypy, ukulahlekelwa ukunyakaza okuzenzakalelayo, ubuso obufihlekile, ukunganaki, ukuthinta okuphansi, ukukhathala, ukuqina, ukukhubazeka kwengqondo, i-micrographia, i-dysgraphia, i-apraxia, ukudangala, ukukhathala,
ukulahlekelwa ukwazi, ukubambezeleka kokukhalipha, i-hyperreflexia, ukulahlekelwa inkumbulo, ubunzima bokugwinya, ukungakwazi ukuzibamba, ukuwa, ukugoba, ukunyakaza, ukuxega, ubuthakathaka bemisipha nokuwohloka, ukungasebenzi kahle kwezimoto, ukulahlekelwa yizinzwa, i-akinetic mutism, nezimpawu zokukhululwa kwe-lobe yangaphambili.
Ukuqala okumaphakathi kwe-parkinsonism ezigulini ezi-5 ku-CARTITUDE-1 kwakuyizinsuku ezingu-43 (ububanzi be-15-108) kusukela ekufakweni kwe-ciltacabtagene autoleucel.
Gada iziguli ukuze uthole izimpawu nezimpawu ze-parkinsonism ezingase zibambezeleke ekuqaleni futhi zilawulwe ngezinyathelo zokunakekela ezisekelayo.
Kunokwaziswa okulinganiselwe kokusebenza ngempumelelo nemithi esetshenziselwa ukwelapha isifo sikaParkinson, ukuthuthukisa noma ukuxazulula izinkinga.
izimpawu ze-parkinsonism ezilandela ukwelashwa kwe-CARVYKTI™.
I-Guillain-Barré Syndrome: Umphumela obulalayo olandela i-Guillain-Barré Syndrome (GBS) wenzeke kolunye ucwaningo oluqhubekayo lwe
ciltacabtagene autoleucel naphezu kokwelashwa nge-intravenous immunoglobulins. Izimpawu ezibikiwe zihlanganisa lezo ezihambisana nokuhluka kwe-MillerFisher kwe-GBS, i-encephalopathy, ubuthakathaka bemisipha, ukuphazamiseka kwenkulumo kanye ne-polyradiculoneuritis.
Gada i-GBS. Linganisa iziguli ezethula i-peripheral neuropathy ye-GBS. Cabangela ukwelashwa kwe-GBS ngezinyathelo zokunakekela ezisekelayo futhi ngokuhambisana nama-immunoglobulins nokushintshisana kwe-plasma, kuye ngobunzima be-GBS.
I-Peripheral Neuropathy: Iziguli eziyisithupha ku-CARTITUDE-1 zakha i-peripheral neuropathy. Lawa ma-neuropathies ethulwa njenge-sensory, motor noma i-sensorimotor neuropathies. Isikhathi esimaphakathi sokuqala kwezimpawu kwakuyizinsuku ze-62 (ububanzi bezinsuku ze-4-136), ubude besikhathi esimaphakathi se-peripheral neuropathies kwakuyizinsuku ze-256 (ububanzi bezinsuku ze-2-465) kuhlanganise nalabo abane-neuropathy eqhubekayo. Iziguli ezihlangabezane ne-peripheral neuropathy nazo zabhekana ne-cranial nerve palsies noma i-GBS kwezinye izivivinyo eziqhubekayo ze-ciltacabtagene autoleucel.
I-Cranial Nerve Palsies: Iziguli ezintathu (3.1%) zaba ne-cranial nerve palsies ku-CARTITUDE-1. Zontathu iziguli zine-7th cranial nerve
ukukhubazeka; esinye isiguli sasine-5th cranial nerve palsy futhi. Isikhathi esimaphakathi sokuqala kwakuyizinsuku ezingama-26 (ibanga lezinsuku ezingama-21-101) kulandela ukumnika
i-ciltacabtagene autoleucel. Ukwenzeka kwe-3rd kanye ne-6th cranial nerve palsy, i-bilateral 7th cranial nerve palsy, ukuwohloka kwe-cranial nerve palsy ngemva kokuthuthukiswa, kanye nokuvela kwe-peripheral neuropathy ezigulini ezine-cranial nerve palsy nakho kuye kwabikwa ezivivinyweni eziqhubekayo.
i-ciltacabtagene autoleucel. Gada iziguli ukuze uthole izimpawu nezimpawu ze-cranial nerve palsies. Cabangela ukuphathwa nge-systemic corticosteroids, kuye ngokuqina nokuqhubeka kwezimpawu nezimpawu. I-Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS: Fatal HLH yenzeke esigulini esisodwa (1%), 99
izinsuku ngemuva kwe-ciltacabtagene autoleucel. Umcimbi we-HLH wandulelwa yi-CRS ende ethatha izinsuku ezingama-97. Ukubonakaliswa kwe-HLH/MAS
zihlanganisa i-hypotension, i-hypoxia enokulimala kwe-alveolar esabalele, i-coagulopathy, i-cytopenia, nokungasebenzi kahle kwezitho eziningi, okuhlanganisa ukungasebenzi kahle kwezinso. I-HLH yisimo esisongela ukuphila esinezinga eliphezulu lokufa uma singabonwa futhi silashwa kusenesikhathi. Ukwelashwa kwe-HLH/MAS kufanele kwenziwe ngokwezindinganiso zesikhungo. I-CARVYKTI™ REMS: Ngenxa yengozi ye-CRS nobuthi be-neurologic, i-CARVYKTI™ itholakala kuphela ngohlelo olukhawulelwe ngaphansi Kwesu Lokuhlola Ubungozi kanye Necebo Lokunciphisa (REMS) elibizwa nge-CARVYKTI™ REMS.
Olunye ulwazi luyatholakala ku-www.CARVYKTIrems.com noma ku-1-844-672-0067.
I-Cytopenias Ende futhi Ephindaphindiwe: Iziguli zingase zibonise i-cytopenias ende futhi ephindaphindiwe elandela i-lymphodepleting chemotherapy kanye ne-CARVYKTI ™ infusion. Isiguli esisodwa senziwe i-autologous stem cell therapy ukuze kubuyiselwe i-hematopoietic ngenxa ye-thrombocytopenia ende.
Ku-CARTITUDE-1, ama-30% (29/97) eziguli athola i-neutropenia yeBanga lesi-3 noma lesi-4 kanye nama-41% (40/97) eziguli athola i-thrombocytopenia yeBanga lesi-3 noma lesi-4 eyayingakaxazululwa ngoSuku lwama-30 kulandela ukumnika kwe-ciltacabtagene autoleucel.
I-neutropenia yeBanga lesi-3 noma lesi-4, i-thrombocytopenia, i-lymphopenia ne-anemia ibonakale ku-63% (61/97), 18% (17/97), 60% (58/97),
kanye nama-37% (36/97) ngemva kokululama kusukela ku-cytopenia yokuqala yeBanga lesi-3 noma lesi-4 kulandela ukumnika. Ngemuva koSuku lwama-60 kulandela i-ciltacabtagene autoleucel
ukumnika, u-31%, u-12% no-6% weziguli waba nokuphindaphinda kweBanga lesi-3 noma i-lymphopenia ephakeme, i-neutropenia ne-thrombocytopenia, ngokulandelana, ngemva kokululama kokuqala kwe-cytopenia yabo yeBanga lesi-3 noma lesi-4. Amaphesenti angamashumi ayisishiyagalombili nesikhombisa (84/97) eziguli abenesiguli esisodwa, ezimbili, noma ezintathu noma ngaphezulu
ukuphindaphinda kweBanga lesi-3 noma i-4 cytopenias ngemva kokululama kokuqala kweBanga lesi-3 noma i-4 cytopenia. Iziguli eziyisithupha neziyi-11 zazine-neutropenia yeBanga lesi-3 noma lesi-4 kanye ne-thrombocytopenia, ngokulandelana, ngesikhathi sokufa.
Gada isibalo segazi ngaphambi nangemuva kokumnika i-CARVYKTI™. Lawula ama-cytopenia anezici zokukhula kanye nokwesekwa kokumpontshelwa komkhiqizo wegazi ngokuya ngemihlahlandlela yesikhungo sendawo.
Ukutheleleka: I-CARVYKTI™ akufanele inikezwe iziguli ezinokutheleleka okusebenzayo noma ukuphazamiseka kokuvuvukala. Izifo ezinzima, ezisongela ukuphila noma ezibulalayo zenzeke ezigulini ngemva kokumnika i-CARVYKTI™.
Ukutheleleka (wonke amabanga) kwenzeka ezigulini ezingama-57 (59%). Ukutheleleka kweBanga lesi-3 noma lesi-4 kwenzeka kuma-23% (22/97) eziguli; Ukutheleleka kweBanga lesi-3 noma le-4 nge-pathogen engashiwongo kwenzeka ku-17%, izifo zegciwane ku-7%, izifo ezibangelwa amagciwane ku-1%, kanye nezifo zefungal ku-1% weziguli.
Sekukonke, iziguli ezine zazinezifo zeBanga lesi-5: ithumba lamaphaphu (n=1), i-sepsis (n=2) kanye nenyumoniya (n=1).
Gada iziguli ukuze uthole izimpawu nezimpawu zokutheleleka ngaphambi nangemva kokumnika i-CARVYKTI™ futhi uphathe iziguli ngendlela efanele. Lawula ama-antimicrobial e-prophylactic, pre-emptive kanye/noma okwelapha ngokuvumelana neziqondiso ezijwayelekile zesikhungo. I-Febrile neutropenia yayikhona
ibonwe ku-10% weziguli ngemva kokumnika i-ciltacabtagene autoleucel, futhi ingase ihambisane ne-CRS. Uma kwenzeka i-febrile neutropenia, hlolela ukutheleleka futhi ulawule ngama-antibiotic abanzi, uketshezi nokunye ukunakekelwa okusekelayo, njengoba kubonisiwe ngokwezokwelapha.
I-Viral Reactivation: Ukuvuselelwa kwegciwane le-Hepatitis B (HBV), kwezinye izimo kubangele isifo sokusha kwesibindi esiphelele, ukwehluleka kwesibindi nokufa, kungenzeka ezigulini ezine-hypogammaglobulinemia. Yenza ukuhlolwa kwe-Cytomegalovirus (CMV), i-HBV, igciwane le-hepatitis C (HCV), kanye ne-human immunodeficiency virus (HIV), nanoma yimaphi amanye ama-ejenti athathelwanayo uma kuboniswe ngokomtholampilo ngokuhambisana neziqondiso zomtholampilo ngaphambi kokuqoqwa kwamaseli ukuze kwenziwe. Cabangela ukwelashwa okulwa namagciwane ukuze uvimbele ukuphinda kusebenze igciwane ngokwemihlahlandlela yesikhungo yendawo/umkhuba wokwelapha.
I-Hypogammaglobulinemia yabikwa njengesenzakalo esibi ku-12% (12/97) yeziguli; Amazinga e-IgG elabhorethri ehle ngaphansi kuka-500 mg/dL ngemva kokumnika ku-92% (89/97) weziguli. Gada amazinga e-immunoglobulin ngemva kokwelashwa nge-CARVYKTI™ futhi unikeze i-IVIG ye-IgG
<400 mg/dL. Phatha imihlahlandlela yesikhungo ngayinye yendawo, okuhlanganisa izinyathelo zokuphepha zokutheleleka kanye nama-antibiotic noma i-antiviral prophylaxis.
Ukusetshenziswa Kwemijovo Ebukhoma: Ukuphepha kokugonywa ngemishanguzo ephilayo yegciwane phakathi noma ngemva kokwelashwa kwe-CRVYKTI™ akukahlolisiswa.
Ukugonywa ngemithi yokugomela igciwane eliphilayo akunconywa okungenani amaviki angu-6 ngaphambi kokuqala kwe-lymphodepleting chemotherapy, ngesikhathi sokwelashwa kwe-CARVYKTI™, futhi kuze kube yilapho amasosha omzimba elulama ngemva kokwelashwa nge-CARVYKTI™.
Ukusabela kwe-Hypersensitivity kwenzeke ku-5% (5/97) yeziguli ezilandela ukumnika kwe-ciltacabtagene autoleucel. Ukusabela okukhulu kwe-hypersensitivity, okuhlanganisa i-anaphylaxis, kungase kube ngenxa ye-dimethyl sulfoxide (DMSO) ku-CARVYKTI™. Iziguli kufanele ziqashwe ngokucophelela amahora ama-2 ngemuva kokumnika ukuze kutholakale izimpawu nezimpawu zokusabela okunzima. Phatha ngokushesha futhi uphathe ngendlela efanele ngokusho kobunzima bokusabela kwe-hypersensitivity.
Izifo Zesibili: Iziguli zingase zibe nezinkinga zesibili. Gada impilo yonke ukuze uthole izifo eziyingozi zesibili. Esimeni lapho kuvela isifo esibulalayo sesibili, thintana no-Janssen Biotech, Inc., ku-1-800-526-7736 ukuze ubike futhi uthole imiyalelo yokuqoqwa kwezidakamizwa.
amasampula esiguli ukuze kuhlolwe ubulwelwe besibili bomsuka we-T cell.
Imithelela Ekhonweni Lokushayela Nokusebenzisa Imishini: Ngenxa yamathuba okuba khona kwezehlakalo ze-neurologic, okuhlanganisa isimo sengqondo esishintshile, ukuquleka, ukuncipha kwe-neurocognitive, noma i-neuropathy, iziguli zisengozini yokuguqulwa noma ukuncipha kokuqaphela noma ukusebenzisana emavikini angu-8 alandelayo.
I-CARVYKTI™ ukumnika. Yeluleka iziguli ukuthi zigweme ukushayela nokwenza imisebenzi eyingozi, njengokusebenzisa imishini esindayo noma engaba yingozi phakathi nalesi sikhathi sokuqala, futhi lapho kuvela khona noma yibuphi ubuthi be-neurologic.
IZIPHENDULO EZIKHULULEKILE
Okuvame kakhulu ukungezwani okungeyona elabhorethri (izigameko ezingaphezu kuka-20%) yi-pyrexia, i-cytokine release syndrome, i-hypogammaglobulinemia, i-hypotension, ubuhlungu bemisipha namathambo, ukukhathala, ukutheleleka kwe-pathogen engashiwongo, ukukhwehlela, ukugodola, isifo sohudo, isicanucanu, i-encephaliteopathy, ukuncipha kwesifiso sokudla. izifo zepheshana lokuphefumula, ikhanda elibuhlungu, i-tachycardia, isiyezi, i-dyspnea, i-edema, izifo ezibangelwa amagciwane, i-coagulopathy, ukuqunjelwa, nokuhlanza. Ukusabela okungekuhle kwaselabhorethri okuvame kakhulu (isigameko esikhulu noma esilingana no-50%) sihlanganisa i-thrombocytopenia, i-neutropenia, i-anemia, ukuphakama kwe-aminotransferase, ne-hypoalbuminemia.
Sicela ufunde Ulwazi Olugcwele Lokunquma kuhlanganise Isexwayiso Esinebhokisi se-CARVYKTI™.
