Purofesa weyunivhesiti yekuRussia ari kumakore ekuma1970 ane chirwere che multiple myeloma. Mushure mekurapwa kakawanda uye kuisirwa autologous kaviri, akadzidza nezvekurapa kweCAR-T kuChina kunorwisa kenza, saka akauya kuChina kuzorapwa neCAR-T cell therapy uye akaburitswa zvakanaka mushure memazuva gumi nematatu ekuisirwazve. Uye munhoroondo yekupedzisira yekutevera, chiremba atoona mamiriro ekuregererwa kwakakwana (CR) mumhedzisiro yake yekuongororwa.
Kurapa neCAR-T, kana kuti chimeric antigen receptor T-cell therapy, inzira huru mukurapa kenza nemasero emunhu. Maitiro aya anosanganisira kuunganidzwa kwemasero eT-cell emurwere, mushure mezvo kuchinjwa kwemajini eT-cells mu in vitro kunoitirwa kuwedzera kugona kwemasero eT kuziva kenza. Masero aya eT-T akagadziriswa (kureva, masero eCAR-T) anobva adzorerwa kumurwere.
KQ-2003 chigadzirwa chekurapa cheBCMA/CD19 chinotarirwa nemasero maviri eCAR T, chichishandisa chimiro cheCAR chazvino-zvino kuti chiwedzere kushanda kwemasero uye kugara kwenguva refu, uye chimiro cheCAR mbiri chinoderedza kudzivirira kwekudzivirira maantigen kubva kukurapa kwega kwega.
Chidzidzo cheInvestigator-Initiated (NCT04714827) muChina chine chinangwa chekuongorora kuchengetedzeka, kushivirira, uye kushanda zvakanaka kwemasero eKQ-2003 CAR-T muvarwere (pts) vane relapse/refractory multiple myeloma (RRMM), kunyanya kune avo vane chirwere chekunze kwemedullary (EMD).
Maitiro
Kuyedzwa uku, kwakagadzirwa nemapoka akawanda, kwakavhurika, kunonyoresa RRMM pts ine ≥1 yekurapa kwakapfuura kunosanganisira proteasome inhibitor (PI), uye immunomodulatory drug (IMiDs), uye/kana anti-CD38. Pts vakagamuchira lymphodepletion ne fludarabine (30 mg/m2/zuva) uye cyclophosphamide (300 mg/m2/zuva) pamazuva -5 kusvika -3, uye ipapo kuiswa kamwe chete kwemasero eKQ-2003 CAR-T (zuva 0) mumazinga matatu edosi (DL) zvichibva pakugadzirwa kwe3+3: DL1, DL2, kana DL3 (1.0, 2.0, kana 3.0×106 CAR+ masero/kg). Chinangwa chaive chekuongorora kuchengetedzeka, kushivirira, kushanda kwekutanga uye hunhu hwePK/PD, uye kuona dosi yakanyanya kushivirira (MTD), toxicity inoderedza dose (DLT). Mhinduro yeropa yakaongororwa zvichienderana neIMWG criteria uye minimal residual disease (MRD) ne new generation flow (NGF). EMD yakaongororwa zvichienderana neProposal Refinement PET Response Criteria.
Mhedzisiro
Kubva pakupera kwekiriniki muna Chikunguru 25, 2024, 23 pts (52.2% yevarume; avhareji yezera remakore 64 (avhareji 52-77)) neRRMM vakagamuchira KQ-2003 (3 DL1, 11 DL2 uye 9 DL3). Nguva yekutevera yaive 13.7 mwedzi (avhareji 2.1-35.2). Pts vakanga vagamuchira avhareji yemitsetse mishanu yekurapwa yapfuura (avhareji 2-11). 91.3% (21/23) vakanga vaine triple-refractory, uye 26.1% (6/23) penta-refractory. 65.2% (15/23) vaiva ne high-risk/ultrahigh-risk cytogenetic profile.
60.9% (14/23) yemapts aiva neEMD pakutanga, kusanganisira 7 extramedullary extraosseous (EM-E), 5 extramedullary-bone related (EM-B), 2 pts pamwe chete neaya ese ari maviri.
Muboka reEMD, 5 pts (5/14, 35.7%) hadzina zviratidzo zvinoyerwa neropa, uye mhinduro yacho yakaongororwa nePET-CT.
Mwero wemhinduro yeropa (ORR) waive 100.0% (18/18), nechiyero che sCR/CR che88.9% (16/18), chiyero cheVGPR che11.1% (2/18). Nguva yepakati kusvika pamhinduro yekutanga yaive 1.2 mwedzi (N=18, chiyero 0.6–3.1; 22.2% ≤1.0 mwedzi), uye nguva yepakati kusvika kuCR/sCR yaive 2.7 mwedzi (N=16, chiyero 0.6–9.1; 50.0% ≤3.0 mwedzi). Pamapts gumi nemapfumbamwe anoongororwa neMRD, 100% yaive isina MRD (10-5), uye chiyero cheMRD-neg chemwedzi mitanhatu nemwedzi gumi nemiviri chaive 80.0%(8/10) uye 100.0%(3/3), zvichiteerana.
PET ORR yeEMD pts yaive 85.7%(12/14), kusanganisira 64.3%(9/14) mhinduro yakakwana yemetabolic (CMR), 21.4% (3/14) mhinduro yemetabolic partial (PMR) uye 14.3% (2/14) chirwere chemetabolic chakasimba (SMD). 64.3% (9/14) uye 50.0% (7/14) yeEMD pts yaive nekudzikira kwe> 50% uye> 75% muhukuru hwe soft tissue plasmacytomas, zvichiteerana. Mu5 EMD pts dzisina zviratidzo zvinoyera hematological, PET ORR yaive 80% (4/5) (2 CMR, 2 PMR uye 1 SMD).
Nguva yepakati yekupindura (DOR) haina kusvika (NR). Mwero we6-most progression-free survival (PFS) uye weoverall survival (OS) waive 86.5% (73.4–100) uye 86.2% (72.8–100), 12-moth PFS uye OS rates waive 75.3% (58.4–97.0) uye 86.2% (72.8–100) zvichiteerana. Avhareji PFS neOS dzaive NR.
Vanhu vana chete ndivo vakafa, kusanganisira vaviri panguva yekudzidza uye vakaongororwa kuti vane chekuita nekurapwa (zvose zviri zviviri pneumonia yakanyanya), uye vaviri vakafa nePD.
CRS neICANS zvakaonekwa zvichiteerana mu21/23 (91.3%, giredhi 3/4 4.3%), uye 5/23 (21.7%, giredhi 3/4 8.7%). Nguva yepakati yekutanga kweCRS yaive 5d (range 1–9) ine avhareji yenguva ye4d (range 1–15). Nguva yepakati yekutanga kweICANS yaive 10d (range 8–23) ine avhareji yenguva ye3d (range 1–9). Hapana DLTs dzakaonekwa.
Nhamba yekopi yemasero eKQ-2003 CAR+ T (VCN) yakaratidza kuti Tmax yepakati yaive 14.0, 11.5, uye 9.0 d muDL1, DL2 uye DL3, zvichiteerana. Cmax yepakati yaive 140.6, 168.2, uye 83.9 makopi/ug DNA uye inogara kwenguva refu. Pakati pemaawa ane mwedzi 6 ne12 yekutevera, 66.7% (10/15) uye 62.5% (5/8) vaive nemasero eCAR+ T aionekwa muropa.
Mhedziso
BCMA/CD19 dual-targeting CAR-T KQ-2003 yakaratidza mhinduro yekutanga, yakadzika uye inogara kwenguva refu muRRMM nekuchengetedzeka kunogamuchirika. Chinonyanya kukosha ndechekuti yakaratidza kushanda kwakanaka muEMD pts, kusanganisira EM-E isingarapiki, iyo inofanirwa kuongororwa zvakanyanya.
Parizvino, kune mimwe miedzo yakawanda yeCAR-T muChina, uye vari kutsvaga varwere. Kuti muwane mazano pamusoro pemishonga mitsva netekinoroji, munogona kubata Beijing South Region Oncology Hospital International Department.
Nhamba yefoni: 4008803716
Imeyili：myimmnet@163.com
Mareferensi
1.http://en.novatim-zj.com/show-28-32-1.html
2.https://ash.confex.com/ash/2024/webprogram/Paper201160.html
3.http://myimm.net/mianyizhiliao/1939.html
Nguva yekutumira: Mbudzi-26-2024