Discussion
in B-cell, HL, neurological adverse reactions, lymphomas, ALL).It, Hodgkin’s lymphoma, ALL, NHL
LYMPHOMAS, ADVERSE EFFECTS, CYTOKINE RELEASE SYNDROME, NHL
These studies aimed to evaluate the safety, PK and activity of AFM11 in two patient populations. There was no evidence of clinical activity in patients with NHL, but biological activity was demonstrated in patients with ALL. Reductions in B-cell populations seen in AFM11-102 are consistent with the expected mode of action of AFM11 and demonstrate that patients received a biologically active dose of AFM11.In contrast to the observations with other T-cell therapies, neither an increase in cytokines nor cytokine release syndrome was noted in patients receiving AFM11. Although the MTD was not formally established either in patients with NHL or in those with ALL, the MTD is likely to have been exceeded as two patients experienced a DLT in the highest dose groups in each study (0.03 μg/kg for patients with NHL and 0.13 μg/kg/week cycle 1 week 1 and 0.4 μg/kg/week cycle 1 week 2 onwards for patients with ALL).It is also acknowledged that neurological side effects are pronounced adverse effects of CD19-targeting T-cell therapies such as blinatumomab, axicabtagene ciloleucil and tisagenlecleucel [At present, several bispecific antibodies that engage T cells or NK cells to enhance the innate immune response are in development, including those being investigated for the treatment of CD30 + lymphomas. This includes a bispecific, tetravalent chimeric antibody construct, AFM13, specifically targets CD30 on Hodgkin’s lymphoma (HL) cells and recruits and activates NK cells by binding to CD16A. In a phase 1 study in patients with R/R HL, AFM13 treatment was well tolerated, and AEs were typically mild or moderate in severity [In conclusion, AFM11 treatment was associated with frequent neurological adverse reactions that were severe in some patients. In ALL, some signs of activity, albeit short-lived, were observed whereas no activity was observed in patients with NHL; therefore, further clinical development was terminated.