Kurapa kweCAR-T Kunokunda Kufungidzira Kusina Kunaka muHigh-Grade B-Cell Lymphoma
Chidzidzo chakabudiswa munguva pfupi yapfuura mu Kufambira Mberi Kweropainoratidza kuti kurapwa nemasero eCAR-T kunopa mabhenefiti akakosha ekurapa kune varwere vane giredhi repamusoro. B-Cell Lymphoma (HGBL), rudzi rwakanyanya kurwadza rwe large B-cell lymphoma (LBCL). Chidzidzo cheDESCAR-T LYSA, chakaitwa nevaongorori vekuFrance, chakanyanya kutarisa varwere vakagamuchira CAR-T therapy senzira yekurapa yechitatu kana kupfuura, kusanganisira avo vane MYC neBCL2 uye/kana BCL6 rearrangements—inozivikanwa se "double-hit" kana "triple-hit" lymphoma.
Chidzidzo ichi chakanyoresa varwere 228 kubva kuFrench DESCAR-T registry, avo 73 vavo vakaonekwa vaine HGBL, nepo vamwe 155 vaive vasina HGBL LBCL. Chinangwa chekudzidza ichi ndechekuongorora kuchengetedzeka uye kushanda kweCAR-T therapy mumapoka aya, neavhareji yenguva yekutevera yemwedzi 18.5.
Zvakawanikwa zvakaratidza kuti huwandu hwemhinduro (ORR) nehuwandu hwemhinduro yakakwana (CR) hwakaenzana pakati pevarwere vane HGBL nevasiri HGBL, pa68% ne60% yeHGBL, uye 76% ne59% yevasiri HGBL, zvichiteerana (p=0.293 uye p=0.923). Uyezve, huwandu hwepakati hwekurarama husina progression-free survival (PFS) hwevarwere vane HGBL hwaive mwedzi 3.2, zvichienzaniswa nemwedzi 4.5 yevarwere vasiri HGBL, kunyangwe musiyano uyu waisakosha zvakanyanya (p=0.103). Saizvozvowo, huwandu hwepakati hwekurarama (OS) hwaive mwedzi 15.4 yevarwere vane HGBL zvichienzaniswa nemwedzi 18.3 yevarwere vasiri HGBL (p=0.214).
Zvinofadza kuti, apo OS yakaverengerwa kubva pazuva iro varwere vakakodzera kurapwa neCAR-T, avhareji yeOS yevarwere veHGBL yakaderera kusvika kumwedzi 7.6, zvichienzaniswa nemwedzi 11.8 yevarwere vasiri HGBL (p=0.062), zvichiratidza kuti nguva yekupa CAR-T ine basa rakakosha mukuvandudza mhedzisiro.
Pakati pemarudzi akasiyana eHGBL, avo vane MYC-BCL2 double-hit lymphoma vaive nemigumisiro yakaipa zvikuru, nepakati peOS yemwedzi 6.6 chete, yakaderera zvakanyanya pane mamwe marudzi eHGBL (HGBL-DH MYC-BCL6: mwedzi 13.6, HGBL-NOS: mwedzi 18.5) uye vasiri varwere veHGBL (mwedzi 11.8). Pasinei neizvi, hapana musiyano wakakosha muOS kana PFS wakawanikwa pakuenzanisa nguva yekuiswa kweCAR-T.
Kuchengetedzwa kwekurapwa neCAR-T kwaive kwakafanana mumapoka ese ari maviri eHGBL neesiri eHGBL. Kuonekwa kwe cytokine release syndrome (CRS) uye immune effector cell-associated neurotoxicity syndrome (ICANS) kwakafanana pakati pemapoka maviri aya. Zvisinei, 38% yevarwere veHGBL vaida kutarisirwa neICU yeCRS, kunyangwe izvi zvakafanana nezvinodiwa pakurapwa zvinoonekwa muvarwere vasiri veHGBL.
Chidzidzo cheDESCAR-T LYSA chinoratidza kugona kwekurapa kweCAR-T mukuvandudza kufambira mberi kwevarwere vane HGBL, kunyangwe mukurapwa kwakazotevera. Kunyange hazvo CAR-T isingakwanise kukunda zvachose kufambira mberi kwakashata kunokonzerwa nemamwe marudzi ane njodzi huru, akadai seHGBL yakarova kaviri, chidzidzo ichi chinokurudzira kupindira nekukurumidza neCAR-T therapy, iyo inogona kupa mhedzisiro iri nani yekurarama. Uyezve, kuderedza nguva iri pakati pe leukapheresis ne CAR-T infusion kunogona kuve kwakakosha kune varwere vane chirwere chakasimba senge HGBL.
Tsvagiridzo iyi inosimbisa kukosha kwekurapa kweCAR-T senzira inoshanda yekurapa B-cell lymphoma yepamusoro uye inopa ruzivo rwakakosha mukugadzirisa nguva yekurapa kuti murwere awane mhedzisiro iri nani. Zvidzidzo zvakawanda zvinodiwa kuti tiongorore nzira dzekuwedzera kushanda kwekurapa kweCAR-T, kunyanya mumhando dzelymphoma dzinonetsa.