Table 1.

In vitro combinatorial effects of tazemetostat with inhibitors of the B-cell receptor pathway and modulators of B-cell activation

Mutant EZH2 GCBWT EZH2 GCBWT EZH2 ABC
ModalityDrug nameWSU-DLCL2KARPAS-422^SU-DHL-10SU-DHL-6OCI-LY19HT#FarageOCI-LY7SU-DHL-5ToledoTMD8OCI-LY3SU-DHL-2
GRAGPrednisoloneSYNSYNSYNSYNSYNN/ESYNSYNSYNN/ESYNSYNSYN
DexamethasoneSYNSYNSYNSYNSYNN/ESYNSYNSYNN/ESYNSYNSYN
B-cell Receptor pathwayEverolimusSYNADDSYNSYNN/ESYNSYNSYNSYNN/ESYNSYNSYN
TrametinibSYNSYNSYNSYNN/EN/ESYNSYNSYNN/ESYNSYNN/E
MK-2206SYNSYNSYNSYNSYNSYNSYNSYNSYNN/ESYNSYNN/E
IbrutinibSYNSYNSYNSYNN/ESYNSYNSYNSYNN/ESYNADDADD
IdelalisibSYNSYNSYNSYNN/ESYNSYNSYNSYNN/ESYNSYNN/E
TamatinibSYNSYNSYNSYNN/ESYNSYNSYNSYNN/ESYNSYNSYN
B-cell ActivatorsCD40LANTANTANTANTN/EANTN/EANTANTSYNSYNN/EANT
LPSANTN/EN/EN/EN/EN/EN/EANTANTSYNANTN/EN/E
BAFFANTN/EN/EANTN/EANTN/EN/EANTN/EANTN/EN/E
APRILANTN/EN/EANTN/EN/EN/EN/EANTN/EANTN/EN/E
Anti-IgM/IgGANTANTN/ESYNN/EN/EN/EN/EN/EN/ESYNN/EN/E
IC50 Tazemetostat 7 day100 nmol/L100 nmol/L50 nmol/L100 nmol/L1 μmol/L500 nmol/L1 μmol/L1.5 μmol/L3.8 μmol/L>10 μmol/L5.5 μmol/L5.1 μmol/L1.3 μmol/L
IC50 Tazemetostat 14 day8.6 nmol/L1.8 nmol/L5.8 nmol/L4.7 nmol/L6.2 μmol/L140 nmol/L99 nmol/L1.4 μmol/L2.1 μmol/L7.6 μmol/L2.6 μmol/L820 nmol/L230 nmol/L
  • NOTE: In vitro assays were performed in the indicated models with 4-day pretreatment with tazemetostat, followed by 3 days of the indicated combination unless otherwise indicated. Synergy (SYN), antagonism (ANT), additivity (ADD) and no combination effect (N/E) were assigned by different methods according to the single-agent activity of tazemetostat and combination partners as described in the Materials and Methods section. SU-DHL-10 and #Farage cell lines used different dosing schedules for combinations (see Materials and Methods Section).