JANUARY 27, 2023—Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a global biotechnology company developing, manufacturing and commercializing novel therapies to treat life-threatening diseases, announced today that CARTITUDE-4, the Phase 3 study evaluating CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) for the treatment of adult patients with relapsed and lenalidomide-refractory multiple myeloma, met its primary endpoint of showing a statistically significant improvement in progression-free survival (PFS) compared to standard therapy at the study’s first pre-specified interim analysis. The study has been unblinded following the recommendation of an independent data monitoring committee.
Ucwaningo lwe-CARTITUDE-4 (NCT04181827) luwucwaningo lokuqala lwamazwe ngamazwe, olungahleliwe, olunelebula evulekile lweSigaba sesi-3 oluhlola ukusebenza kahle nokuphepha kokwelashwa kwe-CAR-T ngokumelene ne-pomalidomide, i-bortezomib ne-dexamethasone (PVd) noma i-daratumumab, i-poxamalidosomide ne-dep. ezigulini ezikhulile ezine-myeloma eminingi ebuyele emuva kanye ne-lenalidomide-refractory eyathola umugqa owodwa kuya kwemithathu yokwelashwa kwangaphambili.
Isiphetho esiyinhloko socwaningo yi-PFS. Iziphetho zesibili zifaka ukuphepha, ukusinda jikelele (OS), izinga elingalungile lesifo esisalayo (MRD) kanye nezinga lokuphendula eliphelele (ORR). Iziguli zizoqhubeka nokulandelwa ezindaweni zokugcina eziyisisekelo nesesibili njengengxenye yocwaningo lwe-CARTITUDE-4.
“Autologous CAR-T cell therapy represents a major breakthrough in cancer treatment, and topline results from CARTITUDE-4 support our continuous efforts to bring this treatment option to patients with i-myeloma eminingi in various stages of disease progression,” Lida Pacaud, M.D., Vice President of Clinical Development and Medical Affairs at Legend Biotech, said.
Imiphumela evela ocwaningweni lwe-CARTITUDE-4 izohanjiswa kumhlangano wezokwelapha ozayo futhi izosekela izingxoxo neziphathimandla zezempilo mayelana nokuhanjiswa kokulawula okungaba khona.
I-CARYKTI® IZIKHOMBISO NOKUSETSHENZISWA
I-CARYKTI® (i-ciltacabtagene autoleucel) iyi-B-cell maturation antigen (BCMA)-eqondiswe ngofuzo iseli ye-autologous T cell immunotherapy ekhonjiswe ekwelapheni iziguli 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.
IZIXWAYISO NEZINYATHELO
CYTOKINE RELEASE SYNDROME (CRS) okuhlanganisa ukusabela okubulalayo noma okusongela ukuphila, kwenzeke 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) lenzeke ku-5% (5/97) weziguli, kanti iBanga lesi-5 le-CRS libikwe esigulini esisodwa. Isikhathi esimaphakathi sokuqala kwe-CRS kwakuyizinsuku eziyi-1 (ububanzi: izinsuku eziyi-7-1). Ukubonakaliswa okuvame kakhulu kwe-CRS kuhlanganisa i-pyrexia (12%), hypotension (100%), ukwanda kwe-aspartate aminotransferase (AST) (43%), ukubandayo (22%), ukwanda kwe-alanine aminotransferase (ALT) (15%) kanye ne-sinus tachycardia ( 14%). Imicimbi yeBanga lesi-11 noma ephakeme ehlotshaniswa ne-CRS yayihlanganisa ukwanda kwe-AST ne-ALT, i-hyperbilirubinemia, i-hypotension, i-pyrexia, i-hypoxia, ukwehluleka ukuphefumula, ukulimala kwezinso okukhulu, ukusatshalaliswa kwe-intravascular coagulation, i-HLH/MAS, i-angina pectoris, i-supraventricular ne-ventricular tachycardia, i-malaise, i-myalgias, ukwanda I-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 yisimo esingase sibeke impilo engozini. 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. Iziguli ezingamashumi amane nane (45%) zithole kuphela i-tocilizumab, kuzo ezingama-33 (34%) 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 i-CARVYKTI® ukumnika esikhungweni sezempilo esiqinisekiswe yi-REMS ngezimpawu 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 Bezinzwa, okungase kube nzima, kusongela ukuphila noma kubulale, kwenzeke 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 kobunye balobu buthi. 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 Effector Cell-Associated Neurotoxicity Syndrome (ICANS): Iziguli zingase zibe ne-ICANS ebulalayo noma esongela ukuphila ngemva kokwelashwa nge-CARVYKTI®, okufaka phakathi ngaphambi kokuqala kwe-CRS, kanyekanye ne-CRS, ngemva kokulungiswa kwe-CRS, noma uma ingekho i-CRS. I-ICANS yenzeke ku-23% (22/97) weziguli ezithola i-ciltacabtagene autoleucel okuhlanganisa imicimbi yeBanga lesi-3 noma lesi-4 kumicimbi engu-3% (3/97) kanye neyeBanga lesi-5 (ebulalayo) 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. Okuvame kakhulu (≥5%) ukubonakaliswa kwe-ICANS kufaka phakathi i-encephalopathy (23%), i-aphasia (8%) kanye nekhanda elibuhlungu (6%).
Gada iziguli okungenani nsuku zonke izinsuku eziyi-10 kulandela i-CARVYKTI® ukumnika endaweni yokunakekelwa kwezempilo eqinisekiswe yi-REMS ngezimpawu 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). Ubuthi be-neurologic ne-parkinsonism buye babikwa kwezinye izivivinyo eziqhubekayo ze-ciltacabtagene autoleucel. Iziguli zazinezimpawu ze-parkinsonian nezingezona eze-parkinsonian ezihlanganisa ukuthuthumela, i-bradykinesia, ukunyakaza okuzenzakalelayo, i-stereotypy, ukulahlekelwa ukunyakaza okuzenzakalelayo, ubuso obufihlekile, ukunganaki, ukuthinta okuphansi, ukukhathala, ukuqina, ukukhubazeka kwengqondo, i-micrographia, i-dysfusionia, i-apraxia, i-lethargy , ukulahlekelwa ukwazi, ukubambezeleka kokusebenza kwengqondo, i-hyperreflexia, ukulahlekelwa inkumbulo, ubunzima bokugwinya, ukungakwazi ukuzibamba kwamathumbu, ukuwa, ukuma ugobile, ukunyakazisa ukuhambahamba, 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. Kunolwazi olulinganiselwe olusebenzayo olunemithi esetshenziselwa ukwelapha isifo sikaParkinson, ukuthuthukisa noma ukuxazululwa kwezimpawu ze-parkinsonism ezilandela i-CARVYKTI.® ukwelashwa.
I-Guillain-Barré Syndrome: Umphumela obulalayo olandela i-Guillain-Barré Syndrome (GBS) wenzeke kolunye ucwaningo oluqhubekayo lwe-ciltacabtagene autoleucel naphezu kokwelashwa ngama-immunoglobulins e-intravenous. Izimpawu ezibikiwe zihlanganisa lezo ezihambisana nokuhluka kwe-Miller-Fisher 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. Zonke iziguli ezintathu zazine-7th cranial nerve palsy; esinye isiguli sasine-5th cranial nerve palsy futhi. Isikhathi esimaphakathi sokuqala kwakuyizinsuku ezingama-26 (ububanzi bezinsuku ezingama-21-101) kulandela ukumnika kwe-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 ze-ciltacabtagene autoleucel. Gada iziguli ukuze uthole izimpawu nezimpawu ze-cranial nerve palsies. Cabangela ukuphathwa nge-systemic corticosteroids, kuye ngokuqina nokuqhubeka kwezimpawu nezimpawu.
HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH)/MACROPHAGE ACTIVATION SYNDROME (MAS): I-HLH ebulalayo yenzeke esigulini esisodwa (1%), izinsuku ezingu-99 ngemva kwe-ciltacabtagene autoleucel. Umcimbi we-HLH wandulelwa yi-CRS ende ethatha izinsuku ezingama-97. Ukubonakaliswa kwe-HLH/MAS kufaka phakathi 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-CARYKTI® REMS: Ngenxa yengozi ye-CRS kanye nobuthi be-neurologic, i-CARVYKTI® itholakala kuphela ngohlelo olukhawulelwe ngaphansi kwe-Risk Evaluation and Mitigation Strategy (REMS) ebizwa nge-CARVYKTI® I-REMS.
I-CYTOPENIAS ESIDE FUTHI EYAQHUBEKA: 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.
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 kanye ne-anemia ibonakale ku-63% (61/97), 18% (17/97), 60% (58/97), kanye nama-37% (36/97) ngemuva kokululama I-cytopenia yokuqala yeBanga lesi-3 noma lesi-4 kulandela ukumnika. Ngemuva koSuku lwama-60 kulandela ukumnika kwe-ciltacabtagene autoleucel, u-31%, u-12% no-6% weziguli zaba nokuphindaphinda kwe-lymphopenia yeBanga lesi-3 noma ngaphezulu, i-neutropenia ne-thrombocytopenia, ngokulandelana, ngemva kokululama kokuqala kwe-cytopenia yabo yeBanga lesi-3 noma lesi-4. Amaphesenti angamashumi ayisishiyagalombili nesikhombisa (84/97) eziguli abe nokuphindaphinda okukodwa, okubili, noma okuthathu noma ngaphezulu kwe-cytopenia yeBanga lesi-3 noma lesi-4 ngemva kokululama kokuqala kweBanga lesi-3 noma lesi-4 i-cytopenia. Iziguli eziyisithupha neziyi-11 zazine-neutropenia yeBanga lesi-3 noma lesi-4 kanye ne-thrombocytopenia, ngokulandelana, ngesikhathi sokufa.
Qaphela ukubala kwegazi ngaphambi nangemuva kwe-CARVYKTI® ukumnika. Lawula ama-cytopenia anezici zokukhula kanye nokwesekwa kokumpontshelwa komkhiqizo wegazi ngokuya ngemihlahlandlela yesikhungo sendawo.
IMIYALO: CARVYKTI® akufanele inikezwe iziguli ezinokutheleleka okusebenzayo noma ukuphazamiseka kokuvuvukala. Izifo ezinzima, ezisongela ukuphila noma ezibulalayo zenzeke ezigulini ngemva kwe-CARVYKTI® ukumnika.
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 kwe-CARVYKTI® infusion and treat patients appropriately. Administer prophylactic, pre-emptive and/or therapeutic antimicrobials according to the standard institutional guidelines. Febrile neutropenia was 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.
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 kubikwe 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 ngesikhathi noma kulandela i-CARVYKTI® Ukwelashwa akuzange kufundwe. Ukugonywa ngemithi yokugomela igciwane bukhoma akunconywa okungenani amaviki angu-6 ngaphambi kokuqala kwe-lymphodepleting chemotherapy, ngesikhathi se-CARVYKTI.® ukwelashwa, futhi kuze kube yilapho amasosha omzimba elulama kulandela ukwelashwa nge-CARVYKTI®.
I-HYPERSENSITIVITY RECTIONS kwenzeke ku-5% (5/97) weziguli 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.
UBUBI LWESIBILI: Iziguli zingase zibe nezinkinga zesibili. Gada impilo yonke ukuze uthole izifo eziyingozi zesibili. Esimeni lapho kuvela isifo esibi sesibili, thintana no-Janssen Biotech, Inc., ku- 1-800-526-7736 ukubika kanye nokuthola imiyalelo yokuqoqwa kwamasampula esiguli ukuze kuhlolwe ubulwelwe besibili bomsuka we-T cell.
IMIPHUMELA YOKUKWAZI UKUSHAYELA NOKUSEBENZISA IMISHINI: Ngenxa yamandla ezenzakalo ze-neurologic, okuhlanganisa isimo sengqondo esishintshile, ukuthuthumela, ukwehla kwe-neurocognitive, noma i-neuropathy, iziguli zisengozini yokuguqulwa noma ukuncipha kokuqaphela noma ukusebenzisana emavikini angu-8 alandela i-CRVYKTI.® 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.
Ukwelashwa kwe-CAR T-Cell iphakathi kokwelashwa okuyimpumelelo kwezinhlobo ezithile zomdlavuza wegazi. Zingaphezu kuka-750 eziqhubekayo izivivinyo zokwelashwa in Ukwelashwa kwe-CAR T-Cell eChina okwamanje. Iziguli ezifisa ukubhalisa zingaxhumana ICancerFax inombolo yosizo yesiguli ku-WhatsApp +91 96 1588 1588 noma nge-imeyili ku info@cancerfax.com.
Sicela ufunde ngokugcwele Kuchaza Ulwazi kufaka phakathi Isexwayiso Esinebhokisi se-CARVYKTI®.
MAYELANA NE-CARVYKTI® (CILTACABTAGENE AUTOLEUCEL; CILTA-CEL)
Ciltacabtagene autoleucel 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 I-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 cilta-cel CAR protein features two BCMA-targeting single domain antibodies designed to confer high avidity against human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.[1]
NgoZibandlela wezi-2017, i-Legend Biotech yangena esivumelwaneni selayisense yomhlaba wonke kanye nesivumelwano sokusebenzisana ne-Janssen Biotech, Inc. (Janssen) sokuthuthukisa nokudayisa i-cilta-cel.
In February 2022, cilta-cel was approved by the U.S. Food and Drug Administration (FDA) under the brand name CARVYKTI® for the treatment of adults with relapsed or refractory multiple myeloma. In May 2022, the European Commission (EC) granted conditional marketing authorization of CARVYKTI® for the treatment of adults with relapsed and refractory multiple myeloma.[3] In September 2022, Japan’s Ministry of Health, Labour and Welfare (MHLW) approved CARVYKTI®.[4] Cilta-cel was granted Breakthrough Therapy Designation in the U.S. in December 2019 and in China in August 2020. In addition, cilta-cel received a PRIority MEdicines (PRIME) designation from the European Commission in April 2019. Cilta-cel also received Orphan Drug Designation from the U.S. FDA in February 2019, from the European Commission in February 2020, and from the Pharmaceuticals and Medicinal Devices Agency (PMDA) in Japan in June 2020. In March 2022, the European Medicines Agency’s Committee for Orphan Medicinal Products recommended by consensus that the orphan designation for cilta-cel be maintained on the basis of clinical data demonstrating improved and sustained complete response rates following treatment.
MAYELANA NE-MYELOMA ENINGI
Multiple myeloma is an incurable umdlavuza wegazi that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells. In 2023, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma, and more than 12,000 people will die from the disease in the U.S. While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.[8] Although treatment may result in remission, unfortunately, patients will most likely relapse. Patients who relapse after treatment with standard therapies, including protease inhibitors, immunomodulatory agents, and an anti-CD38 monoclonal antibody, have poor prognoses and few treatment options available.
[1] I-CARVYKTI™ Ulwazi Lokuchaza. Horsham, PA: Janssen Biotech, Inc.
[2] I-CARVYKTI™ (ciltacabtagene autoleucel), Ukwelashwa Kwe-CAR-T Eqondiswa yi-BCMA, Ithola Ukugunyazwa kwe-US FDA Yokwelapha Iziguli Ezikhulile Nge-Myeloma Ephindaphindekayo noma Ephikisayo. Itholakala ku: https://legendbiotech.com/legend-news/carvykti-ciltacabtagene-autoleucel-bcma-directed-car-t-therapy-receives-us-fda-approval-for-the-treatment-of-adult-patients -ngine-relapsed-noma-refractory-multiple-myeloma/. Ifinyelelwe ngo-Okthoba 2022.
[3] I-CARVYKTI (ciltacabtagene autoleucel) Inikezwe Ukugunyazwa Okunemibandela yiKhomishana YaseYurophu Yokwelashwa Kweziguli Ezine-Myeloma Ephindaphindeka Kabusha futhi Engavumelani. Itholakala ku: https://legendbiotech.com/legend-news/carvykti-ciltacabtagene-autoleucel-granted-conditional-approval-by-the-european-commission-for-the-treatment-of-patients-with-relapsed-and -refractory-multiple-myeloma/. Ifinyelelwe ngo-Okthoba 2022.
[4] I-CARVYKTI™ (ciltacabtagene autoleucel) Ithola Imvume Evela Kumnyango Wezempilo, Wezabasebenzi Nenhlalakahle Yase-Japan (MHLW) Yokwelapha Iziguli Ezine-Myeloma Ephindaphindekayo noma Ephikayo. Itholakala ku: https://www.businesswire.com/news/home/20220926005847/en/CARVYKTI%E2%84%A2-ciltacabtagene-autoleucel-Receives-Approval-from-Japan%E2%80%99s-Ministry-of -Umsebenzi-Wezempilo-Nenhlalakahle-MHLW-Yokwelapha-Iziguli-eziphinde zalapheka-noma-ezine-Refractory-Multiple-Myeloma. Ifinyelelwe ngo-Okthoba 2022.
[5] Ikhomishini yaseYurophu. Irejista Yomphakathi Yemikhiqizo Yemithi Yezintandane. Itholakala ku: https://ec.europa.eu/health/documents/community-register/html/o2252.htm. Ifinyelelwe ngo-Okthoba 2022.
[6] I-American Society of Clinical Oncology. I-Myeloma eminingi: isingeniso. https://www.cancer.net/cancer- types/multiple-myeloma/introduction. Ifinyelelwe ngo-Okthoba 2022.
[7] I-American Cancer Society. "Izibalo Eziyinhloko Mayelana Ne-Myeloma Eningi." Itholakala ku: https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html#:~:text=Multiple%20myeloma%20is%20a%20relatively,men%20and%2015%2C370% 20%20 abesifazane). Ifinyelelwe ngoJanuwari 2023.
[8] I-American Cancer Society. I-Myeloma eminingi: ukutholwa kusenesikhathi, ukuxilongwa kanye nesiteji. https://www.cancer.org/content/dam/CRC/PDF/Public/8740.00.pdf. Ifinyelelwe ngo-Okthoba 2022.
[9] Rajkumar SV. I-Myeloma eminingi: Isibuyekezo sika-2020 sokuxilongwa, ukuhlukaniswa kwengozi nokuphathwa. Ngingu-J Hematol. 2020;95(5),548-567. doi:10.1002/ajh.25791.
[10] Kumar SK, Dimopoulos MA, Kastritis E, et al. Umlando wemvelo we-myeloma ebuyele emuva, i-refractory to immunomodulatory drugs kanye ne-proteasome inhibitors: isifundo se-IMWG se-multicenter. I-leukemia. 2017;31(11):2443-2448.
[11] Gandhi UH, Cornell RF, Lakshman A, et al. Imiphumela yeziguli ezine-multiple myeloma refractory to CD38- targeted monoclonal antibody therapy. I-leukemia. 2019;33(9):2266-2275.
MAYELANA NE-LEGEND BIOTECH
I-Legend Biotech yinkampani yomhlaba wonke ye-biotechnology ezinikele ekwelapheni, futhi ngolunye usuku ukwelapha izifo ezisongela ukuphila. Indlunkulu yethu e-Somerset, eNew Jersey, sakha izindlela zokwelapha ezithuthukisiwe zamaseli kuzo zonke izinkundla zobuchwepheshe ezihlukene, ezihlanganisa i-autologous ne-allogeneic chimeric antigen receptor T-cell, i-gamma-delta T cell (gd T) kanye ne-natural killer (NK) esekelwe kuseli. i-immunotherapy. Kusukela kumasayithi ethu amathathu e-R&D emhlabeni jikelele, sisebenzisa lobu buchwepheshe obusha ukuze siphishekele ukutholwa kwezindlela zokwelapha eziphephile, ezisebenzayo nezisezingeni eliphezulu ezigulini emhlabeni wonke.
