Fischer, LuiseLuiseFischerGrieb, NoraNoraGriebBorn, PatrickPatrickBornWeiß, RonaldRonaldWeißSeiffert, SabineSabineSeiffertBoldt, AndreasAndreasBoldtFricke, StephanStephanFrickeFranz, PaulPaulFranzHeyn, SimoneSimoneHeynKubasch, Anne SophieAnne SophieKubaschBaber, RonnyRonnyBaberWeidner, HeikeHeikeWeidnerWang, Song YauSong YauWangBach, EnricaEnricaBachHoffmann, SandraSandraHoffmannUssmann, JuleJuleUssmannKirchberg, JanineJanineKirchbergHell, SaskiaSaskiaHellSchwind, SebastianSebastianSchwindMetzeler, Klaus H.Klaus H.MetzelerHerling, MarcoMarcoHerlingJentzsch, MadlenMadlenJentzschFranke, Georg-NikolausGeorg-NikolausFrankeSack, UlrichUlrichSackReiche, KristinKristinReicheKöhl, UlrikeUlrikeKöhlPlatzbecker, UweUwePlatzbeckerVucinic, VladanVladanVucinicMerz, MaximilianMaximilianMerz2024-01-152024-01-152024https://publica.fraunhofer.de/handle/publica/45878610.1038/s41375-023-02129-y38184754B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T cells revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM). However, data on cellular (CAR) T cell dynamics and the association with response, resistance or the occurrence of cytokine release syndrome (CRS) are limited. Therefore, we performed a comprehensive flow cytometry analysis of 27 RRMM patients treated with Idecabtagene vicleucel (Ide-cel) to assess the expansion capacity, persistence and effects on bystander cells of BCMA-targeting CAR T cells. Additionally, we addressed side effects, like cytokine release syndrome (CRS) and cytopenia. Our results show that in vivo expansion of CD8+ CAR T cells is correlated to response, however persistence is not essential for durable remission in RRMM patients. In addition, our data provide evidence, that an increased fraction of CD8+ T cells at day of leukapheresis in combination with successful lymphodepletion positively influence the outcome. We show that patients at risk for higher-grade CRS can be identified already prior to lymphodepletion. Our extensive characterization contributes to a better understanding of the dynamics and effects of BCMA-targeting CAR T cells, in order to predict the response of individual patients as well as side effects, which can be counteracted at an early stage or even prevented.enjournal article