Kufunika kwa Zachipatala kwa Mapuloteni a Oligoclonal Pambuyo pa Chithandizo cha BCMA CAR-T mwa Odwala Ambiri a Myeloma
Kumvetsetsa Magulu a Mapuloteni a Oligoclonal mu Chithandizo cha CAR-T
Mu Myeloma yambiri (MM), kupezeka kwa ma protein band osazolowereka (APB), omwe amadziwikanso kuti oligoclonal protein band, kwawonedwa pambuyo poika maselo oyambira a hematopoietic. Komabe, kuchuluka kwawo komanso kufunika kwawo kuchipatala kwa odwala omwe amalandira chithandizo cha maselo a CAR-T cholunjika ku BCMA sikukudziwika bwino. Pofuna kuthana ndi izi, ofufuza ochokera ku Second Affiliated Hospital of Xi'an Jiaotong University adachita kafukufuku wofufuza za kuchuluka kwa APB, mitundu yosiyanasiyana, ndi kufunika kwa kulosera kwa odwala a MM omwe adalandira LCAR-B38M ngati gawo la kafukufuku wa Phase 1 LEGEND-2. Zomwe zapezekazi zidasindikizidwa posachedwapa muHemaSphere, motsogozedwa ndi Mapulofesa He Aili, Wang Fangxia, ndi Bai Ju.
Zomwe Zapezeka
Kafukufukuyu adayesa odwala 47, ndipo 23 (48.9%) adayamba kulandira APB atalandira chithandizo cha CAR-T. Mtundu wofala kwambiri unali IgG (91.3%). Nthawi yapakati yoyambira APB inali miyezi 3.6 pambuyo pa kumwa mankhwala a CAR-T, ndipo nthawi yapakati inali miyezi 5.8. Chofunika kwambiri, kupezeka kwa APB kunagwirizanitsidwa ndi mayankho owonjezereka a chithandizo, kupulumuka kosapitirira muyeso (PFS), komanso kupulumuka konse (OS).
Chidziwitso china chinaphatikizapo:
- Zotsatira Zachipatala ZowonjezerekaOdwala omwe ali ndi APB adawonetsa kuchuluka kwa mayankho abwino ku chithandizo cha LCAR-B38M ndipo adapeza mpumulo waukulu.
- Kubwezeretsa Chitetezo cha Mthupi MwabwinoOdwala a APB adawonetsa kuchuluka kwa ma immunoglobulins ndi ma lymphocytes omwe amachira bwino patatha miyezi itatu ndi isanu ndi umodzi atalandira chithandizo, zomwe zikusonyeza kuti chitetezo chamthupi cha humoral chimayankha bwino komanso chitetezo chamthupi chimabwereranso.
- Zizindikiro za Kulosera ZamtsogoloKusanthula kwa multivariate kunapeza mphamvu ya chithandizo cha CAR-T, kuchuluka kwa ma platelet, kupezeka kwa APB, ndi kuchuluka kwa β2-microglobulin ngati zinthu zodziyimira pawokha zolosera za PFS. Pa OS, mphamvu ya CAR-T ndi kuchuluka kwa ma platelet zinali zinthu zodziyimira pawokha.
Chochititsa chidwi n'chakuti, kafukufukuyu sanapeze kusiyana kwakukulu pakati pa magulu a T-cell kapena NK-cell pakati pa magulu a APB ndi omwe si a APB, zomwe zikusonyeza kuti phindu la APB lingakhale makamaka chifukwa cha kuchira kwa humoral ndi chitetezo chamthupi m'malo mwa njira zodzitetezera ku maselo.
Mapeto ndi Zotsatira zake
Kafukufukuyu akugogomezera kuti kupezeka kwa APB pambuyo pa chithandizo cha BCMA CAR-T kumagwirizana ndi kuchira kwakukulu komanso zotsatira zabwino zachipatala mwa odwala omwe abwereranso/osalandira chithandizo cha MM. Kuphatikiza apo, zomwe zapezekazi zikuwonetsa kuti APB ndi chizindikiro chothandiza pakuchira bwino kwa chitetezo chamthupi pambuyo pa chithandizo, zomwe zimatsegula njira zofufuzira zambiri pakukonza chithandizo cha CAR-T ndikumvetsetsa momwe chitetezo chamthupi chimagwirira ntchito.
Pamene njira zochiritsira za CAR-T zomwe zimayang'aniridwa ndi BCMA zikupitirirabe kusintha, nzeru zotere ndizofunika kwambiri pakukonza njira zochiritsira ndikukweza zotsatira za odwala a MM padziko lonse lapansi.