Ukwelashwa kwe-Cilta-Cel yokwelashwa kwe-myeloma eminingi

Ngoba idalwa ngamaseli akho amhlophe egazi ashintshiwe (aguquliwe) ukuze abone futhi abhubhise amaseli akho amaningi e-myeloma, I-Cilta-Cel CAR T-Cell therapy (i-ciltacabtagene autoleucel) ihlukile kweminye imithi yomdlavuza esetshenziswa njalo (njenge-chemotherapy). 

I-Legend Biotech Corporation ithe i-FDA igunyaze i-ciltacabtagene autoleucel (cilta-cel; Carvykti) njengendlela yokwelapha abantu abadala abane-myeloma ephindaphindekayo noma ephikisayo asebevele benemigqa yokwelapha emine noma ngaphezulu, njenge-proteasome inhibitor, i-immunomodulatory agent, kanye ne-anti-CD38 monoclonal antibody.

I-FDA yelule isikhathi sokubuyekezwa se-cilta-cel, i-chimeric antigen receptor (CAR) T-cell therapy enamasosha omzimba amabili esizinda esisodwa aqondise i-BCMA, kusukela ngo-2021 kuya ku-2023 ukuze kube nesikhathi esanele sokuhlola ulwazi oluthunyelwe mayelana nokuhlaziya okubuyekeziwe. indlela eyenziwe ukuphendula isicelo solwazi se-FDA.

Izinga lokuphendula eliphelele (ORR) lama-98% (95% CI, 92.7% -99.7%) kanye nezinga lokuphendula eliqinile eliqinile (SCR) lama-78% (95% CI, 68.8% -86.1%) atholwe nge-cilta-cel kulawulwa njengokumnika okukodwa ebangeni lethamo elingu-0.5 kuya ku-1.0 x 106 amaseli T asebenzayo e-CAR-positive per kg yesisindo somzimba esigabeni 1/2 sesivivinyo somtholampilo se-CARITUDE (NCT035 Amaseli e-CAR T aveze ukusabela okuqinile nokujulile. ubude besikhathi sokuphendula kwakuyizinyanga ezingu-21.8 (95% CI, 21.8 ukuze zingenakulinganiswa) ekulandeleni okumaphakathi kwezinyanga ezingu-18. 

U-Sundar Jagannath, MD, MBBS, uprofesa wezokwelapha, i-hematology, kanye ne-oncology yezokwelapha eNtabeni yaseSinayi, usebenze njengomphenyi wocwaningo oyinhloko. "Uhambo lokwelapha lweningi leziguli eziphila ne-myeloma eminingi luwumjikelezo ongapheli wokuxolelwa kanye nokubuyela emuva ngeziguli ezimbalwa ezithola impendulo ejulile njengoba zithuthuka emigqeni yokwelapha yakamuva," esho esitatimendeni.

1) Okutholwe ocwaningweni lwe-CARTITUDE-1, okubonise ukuthi i-cilta-cel ingakwazi ukukhiqiza izimpendulo ezijulile neziqinile kanye nezikhawu zamahhala zesikhathi eside, ngisho nakulesi sibalo seziguli eziningi ze-myeloma esilashwe kakhulu, kuye kwavusa isithakazelo sami ngenxa yalokhu. Ukugunyazwa kweCarvykti namuhla kugcwalisa isidingo esibalulekile salezi ziguli.

Abantu abangu-97 abane-myeloma eminingi ebuyele emuva/ephikisayo babeyisihloko selebula evulekile, ingalo eyodwa, ucwaningo lwe-CARITUDE oluphakathi nendawo. Iphesenti leziguli ezihlangabezane nezigameko ezimbi (ama-AE) kanye nephesenti elithole ama-AE anzima asebenze njengezindawo zokugcina eziyisisekelo zesigaba 1. I-ORR isebenze njengendawo yokugcina enkulu yesigaba sesi-2. Abacwaningi bahlole ukusinda kwe-progression-free survival (PFS), ukusinda okuphelele (OS), isikhathi sokuphendula, amazinga amaseli e-CAR-T, amazinga e-BCMA-expressing cells, amazinga e-BCMA encibilikayo, ukugxila kwe-systemic cytokine, amazinga e-BCMA, impilo- ikhwalithi yempilo ehlobene, kanye noshintsho kusukela kukhwalithi yempilo ehlobene nesisekelo njengendawo yokugcina yesibili.

Okutholwe kokulandelela kweminyaka emibili kwalolu cwaningo kusanda kubikwa emhlanganweni waminyaka yonke we-American Society of Hematology. Ngokusho kwedatha, ngokusebenza ngempumelelo, isikhathi esimaphakathi sokusabela kokuqala kwakuyinyanga engu-1, futhi isikhathi esimaphakathi sokuqedela impendulo noma okungcono kwakuyizinyanga ezingu-2 (ububanzi, 1-15). Lapho kuhlolwa ukuba khona kwe-minimum residual disease (MRD) ezigulini ezingama-57, u-91.8% wazo kwatholakala ukuthi awunayo. Izinga le-PFS lalingu-66.0% (95% CI, 54.9% -75.0%) futhi izinga le-OS lalingu-80.9% (95% CI, 71.4% -87.6%) esikhathini sesikhathi sezinyanga ezingu-18. Izinga le-PFS lalingu-96.3% kanti izinga le-OS lalingu-100% eqenjini leziguli ezigcine i-MRD isikhathi esingaphezu kwezinyanga ezingu-6 nangaphezulu kwezinyanga ezingu-12. I-PFS median ayitholakalanga.

2) I-Neutropenia (94.8%), i-anemia (68.0%), i-leukopenia (60.8%), i-thrombocytopenia (59.8%), ne-lymphopenia (49.5%) yayiphakathi kwebanga lesi-3/4 lezehlakalo ezimbi ze-hematological ezabonwa. I-94.8% yeziguli yayine-cytokine release syndrome, eyenzeka kakhulu ebangeni loku-1 nelesi-2.

Ilebula egunyazwe i-FDA ye-cilta-cel ibala i-Guillain-Barré syndrome, i-peripheral neuropathy, cranial nerve palsies, ne-hemophagocytic lymphohistiocytosis ngaphezu kwebanga lesi-3/4 AEs elivamile.

I-FDA yanikeza i-cilta-cel impumelelo kanye nokuqokwa kwesidakamizwa esiyintandane ngaphambi kokusigunyaza ukuze zelashwe iziguli ezine-myeloma eminingi ebuyele emuva noma ephikisayo ezazithole imigqa yokwelashwa emine noma ngaphezulu yangaphambili. I-Cilta-cel nayo ithunyelwe ukuze ivunywe ngaphansi kwalesi sibonakaliso e-Europe.

Isebenza kanjani i-Cilta-Cel CAR T-Cell therapy?

Ukwelashwa kwe-Cilta-Cel I-CAR T-cell therapy, noma ukwelashwa kwe-chimeric antigen receptor, kuwuhlobo olusha lwe-immunotherapy olusebenzisa amaseli e-T aklanywe ngokukhethekile ukuze aqondise ngokunembile amaseli omdlavuza. Amasosha omzimba akhiwe ngamaseli nezitho ezisebenza ndawonye ukuze zigcine umzimba uphephile ekuthelelekeni nasemdlavuzeni. Ama-T cell awuhlobo olulodwa lwengqamuzana oluzingela futhi lubulale amangqamuzana ahlakazekile, kuhlanganise namangqamuzana omdlavuza. Ngenxa yokuthi amangqamuzana omdlavuza kwesinye isikhathi angavika amasosha omzimba, kuyadingeka ukuqeqesha kabusha amasosha omzimba ukuze abone futhi alwe namaseli omdlavuza. I-CAR T-cell therapy iyindlela entsha yokuqeqesha amasosha omzimba ukulwa nomdlavuza.

Ngemva kokuthathwa kwesampula yama-T cell esiguli egazini, amaseli ahlelwa kabusha ukuze abe nezakhiwo ezithile endaweni yawo ezibizwa nge-chimeric antigen receptors (CARs). Ama-receptors kulawa maseli e-CAR T angasiza ama-T cell ekuboneni nasekuhlaseleni amangqamuzana omdlavuza kuwo wonke umzimba lapho ephindiselwa esigulini.

I-CAR T-cell therapy manje isinikezwe ilayisense yi-FDA njengezinga lokunakekela ezinhlotsheni ezithile zokubuyela emuva noma eziphikisayo. I-non-Hodgkin lymphoma, i-myeloma eminingi, kanye ne-pediatric relapsed acute lymphoblastic leukemia (YONKE), futhi ihlolwa ezinhlotsheni ezengeziwe zomdlavuza wegazi.

I-CAR T-Cell therapy iwuhlobo lwe-immunotherapy esebenzisa ama-T-cell ashintshwe ngokukhethekile ayingxenye yamasosha ethu omzimba ukuze alwe. umdlavuza. Isampula yeziguli T amaseli aqoqwa egazini, bese eguqulwa ukuze akhiqize izakhiwo ezikhethekile ezibizwa nge-chimeric antigen receptors (CAR) ebusweni bazo. Lapho la maseli e-CAR ashintshiwe ebuyiselwa esigulini, lawa maseli amasha ahlasela i-antigen ethile futhi abulale amaseli wesimila.

Ziyini izindleko zokwelashwa kwe-Cilta-Cel CAR T-Cell?

Okwamanje, Ukwelashwa kwe-Cilta-Cel CAR T-Cell kubiza cishe u-$225,000 USD e-China kanye ne-$ 425,000 USD e-USA. Okwamanje, itholakala ezikhungweni ezikhethiwe e-US. Kodwa-ke, izivivinyo eziningi zemitholampilo ziyaqhubeka e-China, futhi izindleko zazo kulindeleke ukuthi zehle kakhulu uma lezi zinhlolo ezintsha sezivunyiwe.

Imiphumela engemihle yokwelashwa kwe-Cilta-Cell CAR T-Cell

I-Cilta-Cel (ciltacabtagene autoleucel) kungase kubangele imiphumela engemihle enzima noma esongela ukuphila futhi engaholela ekufeni. Shayela umhlinzeki wakho wezempilo noma uthole usizo oluphuthumayo ngokushesha uma uthola noma yikuphi kokulandelayo:

• imfiva (100.4°F/38°C noma ngaphezulu)
• amakhaza noma ukuqhaqhazela amakhaza
• ukushaya kwenhliziyo okusheshayo noma okungavamile
• ukuphefumula kanzima
• umfutho wegazi ophansi kakhulu
• isiyezi/ikhanda elilula
• imiphumela ohlelweni lwakho lwezinzwa, eminye yayo engenzeka ezinsukwini noma amasonto ngemva kokuthola ukumnika futhi ingase iqale ibe nobuqili, njenge:
  • ukuzizwa udidekile, ungaqaphile kangako noma udidekile, ukuba nenkinga yokukhuluma noma ukukhuluma ngendlela enganakekile, ukuba nenkinga yokufunda, ukubhala nokuqonda amagama, ukulahlekelwa inkumbulo
  • ukulahlekelwa kokuxhumana okuthinta ukunyakaza nokulinganisela, ukunyakaza kancane, izinguquko ekubhaleni ngesandla
  • izinguquko zobuntu, okuhlanganisa ikhono elincishisiwe lokuveza imizwa, ukungakhulumi kakhulu, ukungabi nasithakazelo emisebenzini, nokuncipha kwesimo sobuso
  • ukuntweza, ukuba ndikindiki nobuhlungu ezandleni nasezinyaweni, ukuhamba kanzima, umlenze kanye/noma ubuthakathaka bengalo, nobunzima bokuphefumula.
  • ukuba ndikindiki kobuso, ubunzima bokunyakazisa imisipha yobuso namehlo

I-Cilta-Cel CAR T-Cell therapy e-China

Abalawuli baseShayina banikeze isimo sokwelapha sempumelelo ku-Legend Biotech kanye nokwelashwa kwe-CAR T-cell yophenyo ka-Janssen, i-ciltacabtagene autoleucel (cilta-cel), njengendlela yokwelapha engaba khona ye-myeloma eminingi ebuyele emuva noma ephikisayo.

I-Cilta-cel ibhekisela kukho kokubili i-JNJ-4528, okuyigama ukwelapha okwaziwa ngalo ngaphandle kwaseShayina, kanye ne-LCAR-B38M, okuyigama eyaziwa ngalo e-China.

Isinqumo seNational Medical Products Administration's (NMPA) yaseShayina Yesikhungo Sokuhlola Izidakamizwa (CDE) sihloselwe ukusheshisa ukuthuthukiswa nokubuyekezwa kokwelashwa ngobufakazi bokuqala bomtholampilo besithembiso esikhulu kunokwelashwa kwamanje kwezifo ezibucayi.

Ngokombiko wabezindaba ovela kuLegend, i-CEO uFrank Zhang, PhD, "Ukuqokwa okunconywe yi-China CDE ye-NMPA kubonisa ingqopha-mlando elawulayo ekuthuthukisweni okuqhubekayo kwe-cilta-cel ezigulini eziningi ze-myeloma."

Uqhube wathi, “I-Legend izoqhubeka nokuhlola lokhu kwelashwa kophenyo eChina nakwamanye amazwe ngokubambisana noJanssen.

Ukwelashwa ngaphambilini bekuphethe isitifiketi se-PRIME (Priority Medicines) esivela ku-European Medicines Agency ngenkomba efanayo kanye negama lokwelapha eliphumelelayo elivela ku-US Food and Drug Administration. Ama-ejensi alawulayo e-US, EU, Japan, nase-Korea aphinde ayifake esigabeni somuthi wezintandane.