March 2022: Ukwelashwa kwe-CAR-T, ubuchwepheshe be-CAR-T, yiziphi I-CAR-T cell immunotherapy ? Intengo yokwelashwa kwe-CAR-T, izindleko, isifinyezo sakamuva solwazi lokuqashwa kwesilingo somtholampilo se-CAR-T.
The concept of boron neutron capture therapy has been proposed for decades, but it was not until last year that it really became popular among patients and became a hot spot; the antibody-drug conjugate (ADC), known as a “biomissile”, finally became popular last year. The research on Ukwelashwa kwamaseli e-CAR-T ubuye wadlula iminyaka eminingi, kodwa kusukela ngonyaka odlule, ikakhulukazi kusukela engxenyeni yesibili yonyaka odlule, inani elikhulu Izindlela zokwelapha ze-CAR-T have been “combined.”. Anti-cancer “new forces” are rapidly emerging.
U-Emily Whitehead, ingane yokuqala ene-leukemia elashwa ngayo I-CAR-T yokwelapha futhi “umkhulumeli” wokwelashwa kwe-CAR-T, uye wehlula i-leukemia cishe iminyaka eyishumi. Manje lokhu kwelashwa “okuyisimangaliso” sekufike kuye eduze kweziguli zethu.
Kusukela ngo-2021 kuze kube manje, ukwelashwa kwe-CAR-T kubonise ukuthambekela kokunqwabelana, futhi imikhiqizo eminingi yethulwe ngokulandelana. Ngalesi sikhathi, izwe lami selingenise izindlela zokwelapha ezi-3 ze-CAR-T ngokulandelana, okuvumela iziguli ukuthi zibone ukuqala kohlelo olusha.
Liso-Cel
(I-Lisocabtagene maraleucel, Breyanzi)
Isimo: Kugunyazwe ukumaketha (i-FDA)
Nini: February 6, 2021
Isingeniso: I-Liso-Cel iwukwelapha okulwa ne-CD19 okusekelwe kuma-T cell esiguli.
Indications: Large B-cell i-lymphoma (adult patients with some types of large B-cell lymphoma who have not responded to at least 2 other types of systemic therapy or have relapsed after therapy)
Kuyasebenza izivivinyo zokwelashwa kanye nedatha:
[TRANSCEND NHL 001 trial (NCT02631044)] Ezigulini ezelashwa nge-Liso-Cel, izinga lokuxolelwa lilonke lalingu-73%, lapho izinga lokuxolelwa okuphelele lalingaphezu kwama-53%; iziguli zingazuza ukukhululwa kokuqala noma ukukhululwa ingxenye ngemva kokwelashwa cishe kwenyanga engu-1.
Ekulandeleni okuphakathi kwezinyanga ze-12, i-54.7% yeziguli zahlala ekukhululweni komtholampilo; iziguli zazinokusinda okuphakathi kwezinyanga ezingu-6.8 kanye nokuphila okuphakathi kwezinyanga ezingu-21.1; iziguli zinezinga lokusinda lonyaka ongu-1%.
I-Axi-Cel
(Axicabtagene ciloleucel, Yescarta)
Isimo: Kugunyazwe ukumaketha (i-FDA)
Nini: Mashi 5, 2021
Introduction: The FDA has granted Yescarta, a CAR-CD19 T cell therapy, breakthrough therapy designation and priority review for the indication of follicular lymphoma. The FDA has previously approved Yescarta’s indication for large B-cell lymphoma. After this approval, Yescarta became the first I-CAR-T cell immunotherapy ku-follicular lymphoma.
Izinkomba: I-Follicular lymphoma (i-follicular lymphoma ebuyele emuva noma i-refractory, iziguli ezikhulile, ngemva kokwelashwa okuhleliwe okubili noma ngaphezulu)
Kuyasebenza izivivinyo zokwelashwa kanye nedatha:
[Isivivinyo se-ZUMA-5] Izinga lokuphendula lilonke lifinyelele ku-91%, futhi izinga lokuphendula eliphelele laliphezulu njenge-60%; isikhathi esimaphakathi sokuphendula asifinyelelwanga ekulandeleni okuphakathi kwezinyanga ze-14.5, futhi i-74% yeziguli inesikhathi sokuphendula esingaphezu kwezinyanga ze-18.
Isimo: Kugunyazwe Ukumaketha (i-FDA, Ilayisense Ye-Supplemental Biologics)
Inkomba: Irejimeni yomthamo ophezulu wokwelashwa komugqa wesibili weziguli ezikhulile ezine-B-cell lymphoma ebuyele emuva/ephikisayo
Ide-cel
(Idecabtagene vicleucel, Abecma)
Isimo: Kugunyazwe ukumaketha (i-FDA)
Nini: Mashi 26, 2021
Isingeniso: I-Abecma iyi-autologous eqondiswe yi-BCMA i-chimeric antigen receptor (CAR) T cell therapy enziwe ngokwezifiso kuma-T cell esiguli.
Izinkomba: I-myeloma eminingi (adult patients with relapsed or refractory multiple myeloma who have received 4 or more lines of therapy, including immunomodulators, proteasome inhibitors and CD38 monoclonal antibodies)
Izivivinyo zomtholampilo ezifanele kanye nedatha:
[Ucwaningo olusezikhungweni eziningi] Izinga lokuxolelwa kwazo zonke iziguli lalingu-72%, lapho izinga lokukhululwa okuphelele lalingu-28%; phakathi kweziguli ezithole ukukhululwa okuphelele emtholampilo, ama-65% eziguli aye axolelwa isikhathi esingaphezu kwezinyanga eziyi-12.
I-KTE-X19
(Brexucabtagene Autoleucel, Tecartus)
Isimo: Kugunyazwe ukumaketha (i-FDA)
Nini: Okthoba 1, 2021
Introduction: A CAR-CD19 T cell therapy previously approved for the treatment of i-mantle cell lymphoma.
Izinkomba: I-B lymphocytic leukemia (iziguli ezikhulile ezine-leukemia ye-lymphocytic ephindaphindiwe futhi ephikisayo)
Izivivinyo zomtholampilo ezifanele kanye nedatha:
[ZUMA-3 trial] The complete remission rate was 56.4%, and 14.5% of patients achieved clinical complete remission. Only the blood counts did not return to normal, that is, CRi was achieved; the median progression-free survival was 11.6 months, and the median overall survival was 18.2 months. Patients who achieved clinical complete remission (including blood counts that did not return to normal) had a median progression-free survival of 14.2 months and had the shortest overall survival of 16.2 months; for those who did not, the median overall survival was only 2.4 months..
Yijililenxe Umjovo
(Aquilon Race; Yescarta, Axicabtagene Ciloleucel, Axi-Cel; FKC876)
Isimo: Igunyazwe Ukumaketha (NMPA)
Nini: Juni 23, 2021
Intengo: 190,000 USD
Isingeniso: Umkhiqizo wokuqala wamaseli e-CAR-T owethulwe eShayina i-CAR-CD19-T cell therapy.
Ukubaluleka: For adults with relapsed or refractory large B-cell lymphoma after receiving second-line or above standard therapy, this medicine is indicated. It can be used for diffuse large B-cell lymphoma unspecified, primary mediastinal B-cell carcinoma lymphoma isisu, high-grade B-cell lymphoma, and diffuse large B-cell lymphoma transformed from follicular lymphoma.
Izivivinyo zomtholampilo ezifanele kanye nedatha: [Isivivinyo se-ZUMA-5] Izinga lokuphendula lilonke lifinyelele ku-91%, futhi izinga lokuphendula eliphelele laliphezulu njenge-60%; isikhathi esimaphakathi sokuphendula asifinyelelwanga ekulandeleni okuphakathi kwezinyanga ze-14.5, futhi i-74% yeziguli inesikhathi sokuphendula esingaphezu kwezinyanga ze-18.
I-Ruiki Orenza Injection
(Relma-cel, JWCAR029)
Isimo: Igunyazwe Ukumaketha (NMPA)
Nini: Septhemba 3, 2021
Intengo: 200,000 USD
Isingeniso: Umkhiqizo wesibili wamaseli e-CAR-T wethulwa eShayina, kanye nokwelapha kokuqala kwasekhaya kwe-CAR-CD19-T okugunyazwe ngokusemthethweni ukumakethwa, kwathuthukiswa yi-Shanghai WuXi Junuo.
Izinkomba: I-B-cell lymphoma enkulu (iziguli ezindala ezine-B-cell lymphoma enkulu ebuyele emuva noma ephikisayo ngemva komugqa wesibili noma ngaphezulu kokwelashwa kwe-systemic)
Izivivinyo zomtholampilo ezifanele kanye nedatha:
Izinga lokuphendula lilonke lalingama-60.3%.
I-Sidaki Aurexa Injection
(LCAR-B38M, JNJ-4528, Cilta-cel, Carvykti)
Isimo: Igunyazwe Ukumaketha (NMPA)
Nini: February 28, 2022
Intengo: US$465,000/inaliti
Isingeniso: Umkhiqizo wesithathu wamaseli e-CAR-T owethulwe eShayina uwumuthi we-CAR-BCMA-T othuthukiswe ngokuhlanganyela ngu-Janssen kanye no-Legend Bio.
Indications: Multiple myeloma (adult patients with relapsed/refractory multiple myeloma. Relevant clinical trials and data:
Izinga lokuphendula lilonke lalingama-98%, lapho ama-83% eziguli athola impendulo eqinile ephelele; izinga lokusinda lezinyanga eziyi-18 lalingama-66%, kanti izinga lokusinda leminyaka engu-2 lalingama-61%; izinga lokusinda lezinyanga eziyi-18 lilonke lalingama-81 %, kanti izinga lokusinda leminyaka emi-2 lilonke lalingama-74%.
Ngokungeziwe kule mikhiqizo esohlwini olungenhla, kunemikhiqizo eminingi yamaseli e-CAR-T esesigabeni sangaphambi kokumakethwa, eqongelela kancane kancane idatha yesilingo somtholampilo, noma ethumele isicelo sokumaketha, futhi okusele nje kuyisinyathelo sokuhlangana neziguli ngokusemthethweni.
Among them, there are many “rookies” with potential as much as the marketed products, and during this period they have obtained various FDA licenses or “titles,” such as orphan drug designation, fast track qualification, advanced regenerative immune therapy, and so on.
I-Cilta-cel
(Ciltacabtagene autoleucel, domestic name: Ciltacabtagene autoleucel injection)
Isimo: (FDA) Ukubuyekezwa Okubalulekile
Izinkomba: I-Myeloma eminingi (i-myeloma ephindaphindayo/eyehlayo)
Isingeniso: I-CAR-BCMA-T Cell Therapy
Izivivinyo zomtholampilo ezifanele kanye nedatha:
[Isivivinyo se-CARTITUDE-1] Izinga lokuphendula lilonke lalingama-98%, lapho ama-83% eziguli athola impendulo eqinile ephelele; izinga lokusinda lezinyanga eziyi-18 lalingama-66%, kanti izinga lokusinda leminyaka engu-2 lalingama-61%; izinga lokusinda lezinyanga eziyi-18 lilonke lalingama-81 %, kanti izinga lokusinda leminyaka emi-2 lilonke lalingama-74%.
I-ALLO-715
Isimo: (FDA) Ukuqokwa kwe-RMAT, Ukuqokwa Kwezidakamizwa Zentandane
Izinkomba: I-Myeloma eminingi (i-myeloma ephindaphindayo/eyehlayo)
Isingeniso: I-CAR-BCMA-T Cell Therapy
Izivivinyo zomtholampilo ezifanele kanye nedatha:
Isilingo se-UNIVERSAL: Ezigulini ezithole u-3.2×10^6 (izigidi ezingu-320) zokujova amaseli e-CAR-T, izinga lokuphendula lilonke lifinyelele ku-60%. Inombolo emaphakathi yemigqa yokwelapha yeziguli yayingu-5.
UKymriah
(Tisagenlecleucel)
Isimo: (FDA) Ukubuyekezwa Okubalulekile Kwezinkomba Ezintsha
Izinkomba: i-follicular lymphoma (ukwelashwa komugqa wesibili noma ngaphezulu kwe-lymphoma ephindaphindayo noma ephikisayo)
Isingeniso: Ukwelashwa kwamaseli e-CAR-CD19-T, okugunyazwe iziguli ezikhulile ezine-B-cell lymphoma enkulu ebuyele emuva/esabelayo.
Izivivinyo zomtholampilo ezifanele kanye nedatha:
[JULIET trial] The overall remission rate of 613 patients was 57.4%, of which 42.4% were in complete remission.
I-CTX110
Isimo: (FDA) Ukuqokwa kwe-RMAT
Izinkomba: I-B-cell malignancies (i-CD19-positive B-cell malignancies ephindaphindayo)
Isingeniso: I-Allogeneic CAR-CD19-T Cell Therapy
Izivivinyo zomtholampilo ezifanele kanye nedatha:
[CARBON Trial] Among 24 patients who met the intention-to-treat criteria, the overall response rate of CTX110 in the second dose group was 58%, including 38% of patients who achieved a clinically complete response.
I-CT120
Isimo: (FDA) Ukuqokwa Kwezidakamizwa Zentandane
Inkomba: i-leukemia enamandla ye-lymphoblastic
Introduction: CD19/CD22 Dual Targeting Chimeric Antigen Receptor (CAR) T Cell Therapy
I-C-CAR039
Isimo: (FDA) Ukuqokwa kwe-RMAT, Ithrekhi Esheshayo
Izinkomba: Sabalalisa i-B-cell lymphoma enkulu
Isingeniso: CD19/CD20 Dual Targeting Chimeric Antigen Receptor-T Cell Therapy
Izivivinyo zomtholampilo ezifanele kanye nedatha:
【Isivivinyo seSigaba I】Izinga lokuphendula eliphelele leziguli ezine-lymphoma enkulu ye-B-cell ehlehlisiwe noma eyeqisayo lalingu-91.7%, okuyizinga lokuphendula eliphelele libe ngu-83.3%.
I-CT103A
Isimo: (FDA) Ukuqokwa Kwezidakamizwa Zentandane
Isibonakaliso: i-myeloma eminingi
Isingeniso: I-CAR-BCMA-T Cell Therapy
Izivivinyo zomtholampilo ezifanele kanye nedatha:
[Isivivinyo seSigaba I] Phakathi kweziguli ezingu-18 ezine-myeloma ephindaphindiwe kanye/noma ephikisayo, izinga lokuphendula eliphelele le-CT103A laliyi-100%, lapho i-72.2% yeziguli ifinyelele izinga lokuphendula okuphelele; izinga lokusinda lonyaka ongu-1 lokungaqhubeki libe ngu-58.3 %.
Liso-Cel
(Lisocabtagene maraleucel, Breyanzi)
Isimo: (FDA) Ukubuyekezwa Okubalulekile, yamukele isicelo sokugunyazwa ukumaketha
Isingeniso: I-CAR-CD19-T Cell Therapy
Inkomba: I-B-cell lymphoma enkulu (iziguli ezikhulile ezine-B-cell lymphoma enkulu ebuyele emuva noma ephikisayo ezehlulekile ukwelashwa komugqa wokuqala)
So far, all CAR-T cell therapies that have been marketed have targeted various types of hematological tumors. Even if promising therapies are included, there are very few projects targeting solid tumors. It is so difficult for CAR-T therapy to break through solid tumors, and only a few “elites” can be on this most difficult “battlefield.”.
I-CT041
Isimo: (FDA) Ukuqokwa kwe-RMAT, Ukuqokwa Kwezidakamizwa Zentandane
Indications: Gastric cancer (Claudin18.2 positive advanced gastric cancer and gastroesophageal junction i-adenocarcinoma)
Isingeniso: I-CAR-Claudin 18.2-T Cell Therapy
Izivivinyo zomtholampilo ezifanele kanye nedatha:
Izinga lokuphendula eliphelele lazo zonke iziguli lalingu-48.6%, futhi izinga lokulawula izifo lalingu-73%; izinga lokuphendula lazo zonke iziguli ezinomdlavuza wesisu lalingama-57.1%. Izinga lokusabela lilonke leziguli ezinomdlavuza wesisu ezahluleka okungenani imigqa emi-2 yokwelapha esikhathini esedlule lalingu-61.1%, futhi izinga lokulawula izifo lalingama-83.3%.
There is no doubt that CT041 is one of the most advanced and effective regimens among all CAR-T cell therapies for solid tumors. At present, this program is still recruiting subjects, and patients who have the opportunity to try it must not miss it!
I-AIC100
Isimo: (FDA) Ithrekhi Esheshayo
Izinkomba: Umdlavuza we-Thyroid (anaplastic thyroid cancer and refractory, poorly differentiated thyroid cancer)
Isingeniso: I-CAR-ICAM-1-T Cell Therapy
There are three CAR-T products currently listed in China: one is 1.2 million per injection, the other is 1.29 million per injection, and the third is US$465,000 per injection. For the vast majority of patients, i’s an unbearable price.
The cost of CAR-T therapy is obviously expensive, but at the same time, my country is the country with the largest number of CAR-T cell therapy research and clinical trials, and a large number of domestic centers are recruiting Chinese patients for trial projects. For patients who meet the needs of the indication, this is a good channel to enjoy new drug treatments in advance and avoid huge expenses.
