Haematology laboratory parameters to assess efficacy of CD19‐, CD22‐, CD33‐, and CD123‐directed chimeric antigen receptor T‐cell therapy in haematological malignancies

Introduction Chimeric antigen receptor (CAR) T cell products are available to treat relapsed/refractory B‐lymphoblastic leukaemia/lymphoma (B‐ALL), diffuse large B‐cell lymphoma, mantle‐cell lymphoma, and myeloma. CAR products vary by their target epitope and constituent molecules. Hence, there are no common laboratory assays to assess CAR T cell expansion in the clinical setting. We investigated the utility of common haematology laboratory parameters to measure CAR T cell expansion and response. Methods Archived CellaVision images, absolute lymphocyte counts, and Sysmex CPD parameters spanning 1 month after CD19‐CAR, UCAR19, CD22‐CAR, CD33‐CAR, and UCAR123 therapy were compared against donor lymphocyte infused control patients. Additionally, CellaVision images gathered during acute EBV infection were analysed. Results CellaVision images revealed a distinct sequence of three lymphocyte morphologies, common among CD19‐CAR, CD22‐CAR and UCAR19. This lymphocyte sequence was notably absent in CAR T cell non‐responders and stem‐cell transplantation controls, but shared some features seen during acute EBV infection. CD19‐CAR engraftment kinetics monitored by quantitative PCR show an expansion and persistence phase and mirror CD19‐CAR ALC kinetics. We show other novel CAR T cell therapies (UCAR19, CD22‐CAR, CD33‐CAR and UCAR123) display similar ALC expansion in responders and diminished ALC expansion in non‐responders. Furthermore, the CPD parameter LY_WY fluorescence increased within the first week after CD19‐CAR infusion, preceding the peak absolute lymphocyte count (ALC) by 3.7 days. Conclusion Autologous and allogeneic CAR T cell therapy produce unique changes in common haematology laboratory parameters and could be a useful surrogate to follow CAR T‐cell expansion after infusion.