Targeted therapies in development for DLBCL and FL
| Molecular feature . | Driver of DLBCL or FL? . | Targeted therapeutics in development . | Reference . | Clinical trial number . |
|---|---|---|---|---|
| BCL2 expression | ABC and GCB DLBCL and FL | ABT-199, navitoclax, IMC-48 | 13-15 | NCT01328626, NCT00788684 |
| MYC and either BCL2 or BCL6 expression (“double hit”) | ABC and GCB DLBCL | BET inhibitors (eg, OTX015), TMPyP4 | 16-19 | NCT01713582 |
| CXCR4 expression | ABC and GCB DLBCL and FL | BKT140, AMD3100, BKM120 | 20-23 | |
| PTEN inactivation | GCB DLBCL and FL; uncommon in ABC DLBCL | PI3K inhibitors (eg, BKM120), mTOR inhibitors (eg, everolimus), AKT inhibitors | 23, 24 | NCT01719250, NCT0204954, NCT01693614, NCT00869999 |
| EZH2 mutation | GCB DLBCL and FL | EPZ-6438, GSK2816126 | 25, 26 | NCT01897571, NCT02082977 |
| Loss of EPHA7 expression | ABC and GCB DLBCL and FL | Recombinant EPHA7 | 27 | |
| Constitutive activation of NF-κB signaling | ABC DLBCL and FL | Bortezomib | 28, 29 | NCT00057902, NCT00715208 |
| Constitutive activation of B-cell receptor signaling | ABC DLBCL and FL | Ibrutinib | 30, 31 | NCT01804686, NCT01569750 |
| Molecular feature . | Driver of DLBCL or FL? . | Targeted therapeutics in development . | Reference . | Clinical trial number . |
|---|---|---|---|---|
| BCL2 expression | ABC and GCB DLBCL and FL | ABT-199, navitoclax, IMC-48 | 13-15 | NCT01328626, NCT00788684 |
| MYC and either BCL2 or BCL6 expression (“double hit”) | ABC and GCB DLBCL | BET inhibitors (eg, OTX015), TMPyP4 | 16-19 | NCT01713582 |
| CXCR4 expression | ABC and GCB DLBCL and FL | BKT140, AMD3100, BKM120 | 20-23 | |
| PTEN inactivation | GCB DLBCL and FL; uncommon in ABC DLBCL | PI3K inhibitors (eg, BKM120), mTOR inhibitors (eg, everolimus), AKT inhibitors | 23, 24 | NCT01719250, NCT0204954, NCT01693614, NCT00869999 |
| EZH2 mutation | GCB DLBCL and FL | EPZ-6438, GSK2816126 | 25, 26 | NCT01897571, NCT02082977 |
| Loss of EPHA7 expression | ABC and GCB DLBCL and FL | Recombinant EPHA7 | 27 | |
| Constitutive activation of NF-κB signaling | ABC DLBCL and FL | Bortezomib | 28, 29 | NCT00057902, NCT00715208 |
| Constitutive activation of B-cell receptor signaling | ABC DLBCL and FL | Ibrutinib | 30, 31 | NCT01804686, NCT01569750 |
Listed are only those agents discussed in this article. More comprehensive listings of targeted therapeutics in development can be found in recent reviews.32,33
AKT, protein kinase B; BET, bromodomain and extraterminal domain; mTOR, mechanistic target of rapamycin; NF, nuclear factor; PI3K, phosphatidylinositol 3-kinase.