Combination benefit with CHOP components and EPZ-6438 in <i>EZH2</i> mutant germinal center B-cell lymphoma cell lines.

<p>Combination index (CI) graphs, generated in Calcusyn, of EPZ-6438 with Mafosfamide, Doxorubicin, or Vincristine in the <i>EZH2</i> Y646F mutant cell lines WSU-DLCL2 (A–C) or SUDHL10 (D–F). The 95% confidence interval is displayed in each graph (representative of 2 biological replicates for each cell line). The fractional effect (Fa) plotted is the fraction of cell growth (inhibition) resulting from a compound treatment, calculated from the DMSO control. A) Additivity was induced for the EPZ-6438/Mafosfamide combination at a 1∶20 constant ratio (doses were 16–125 nM for EPZ-6438 and 313–2500 nM for Mafosfamide). B) Synergy was induced for the EPZ-6438/Doxorubicin combination at a 50∶1 constant ratio (doses were 16–500 nM for EPZ-6438 and 0.3–10 nM for Doxorubicin). C) Additivity was induced for the EPZ-6438/Vincristine combination at a 400∶1 constant ratio (doses were 16–1000 nM for EPZ-6438 and 0.39–2.5 nM for Vincristine). D) Additivity was induced for the EPZ-6438/Mafosfamide combination at a 4∶25 constant ratio (doses were 12.5–200 nM for EPZ-6438 and 78–1250 nM for Mafosfamide). E) Additivity was induced for the EPZ-6438/Doxorubicin combination at a 10∶3 constant ratio (doses were 3–50 nM for EPZ-6438 and 0.94–15 nM for Doxorubicin). F) Additivity was shown for the EPZ-6438/Vincristine combination at an 800∶1 constant ratio (doses were 12.5–200 nM for EPZ-6438 and 15.6–250 pM for Vincristine).