SESSION 1: NEW THERAPEUTICS
J. W Choi, S Corcoran, B Wang, Björ Häupl, et al.
The study authors have uncovered that CSK functions as a positive BCR signaling regulator that sustains active SFKs in the context of oncogenic BCR signaling. They conclude that CSK inhibition, by blocking proximal BCR signaling, represents a novel therapeutic strategy for aggressive lymphomas that is non-redundant with existing agents now used to treat these cancers.
MALT1 DEGRADATION FOR THE TREATMENT OF ACTIVATED B-CELL TYPE DIFFUSE LARGE B-CELL LYMPHOMA abstract
M. R Seshadri, L Fontán, D Scott, J Hatcher, et al.
The study authors report a PROTAC compound that induces potent degradation of MALT1 without degradation of IMiD-induced CRBN neosubstrates, associated with selective suppression of ABC-DLBCL cell lines and inhibition of the NF-κB pathway. their findings suggest that MALT1 degradation is a promising strategy for the treatment of ABC-DLBCL and warrants further development.
KT-413, A NOVEL IRAKIMID DEGRADER OF IRAK4 AND IMID SUBSTRATES, HAS A DIFFERENTIATED MOA THAT LEADS TO SINGLE-AGENT AND COMBINATION REGRESSIONS IN MYD88MT LYMPHOMA MODELS abstractM Mayo, R Karnik, C Klaus, K Sharma, A McDonald, D. H Walker, M Weiss
FIRST-IN-HUMAN STUDY OF THE EZH1 AND EZH2 DUAL INHIBITOR VALEMETOSTAT TOSYLATE (DS-3201B) IN PATIENTS WITH RELAPSED OR REFRACTORY NON-HODGKIN LYMPHOMAS abstract
K Ishitsuka, K Izutsu, D Maruyama, S Makita,
The study authors demonstrate that Valemetostat showed an acceptable safety profile in patients with R/R NHLs and encouraging preliminary efficacy in patients with R/R PTCL or ATL.
GLOFITAMAB STEP-UP DOSING: UPDATED EFFICACY DATA SHOW HIGH COMPLETE RESPONSE RATES IN HEAVILY PRETREATED RELAPSED/REFRACTORY (R/R) NON-HODGKIN LYMPHOMA (NHL) PATIENTS abstract
C Carlo-Stella, M Hutchings, F. C Offner, F Morschhauser, et al.
The study authors conclude that updated data for glofitamab monotherapy SUD show higher preliminary response rates than previously reported in patients with R/R NHL who have failed multiple lines of therapy. Cytokine release syndrome was mostly manageable, of low grade, and confined to the first cycle of treatment.
SUBCUTANEOUS EPCORITAMAB IN PATIENTS WITH RELAPSED/REFRACTORY B-CELL NON-HODGKIN LYMPHOMA: SAFETY PROFILE AND ANTI-TUMOR ACTIVITY abstract
M Hutchings, R Mous, M. R Clausen, P Johnson,
The study authors conclude that with longer follow-up, SC epcoritamab demonstrated substantial single-agent activity, inducing deep and durable clinically meaningful responses, with a consistent safety profile. No severe (grade ≥3) cytokine release syndrome events, no febrile neutropenia, and limited neurotoxicity was observed.