Table 5.
Targeted therapy for DHL-BCL6
| Category | Target | Agent | Stage of development | References |
|---|---|---|---|---|
| Notch | γ-secretase | MK-0752 | Phase I (CLL, terminated) | NCT00100152 |
| Z-LLNle-CHO | Preclinical (precursor B-cell acute leukemia) | [290] | ||
| Z-IL-CHO | Preclinical (DLBCL) | [291] | ||
| Unidentified | Crenigacestat | Phase I /II (multiple myeloma and precursor T-cell lymphoblastic leukemia) | ||
| Unidentified | CB-103 | Phase I (NHL) | NCT03422679 | |
| BCR signaling | BTK | Ibrutinib | Approval for mantle cell lymphoma, Chronic lymphocytic leukemia/small lymphocytic lymphoma, DLBCL | |
| SYK | Fostamatinib Disodium (R788) | Approval for DLBCL | ||
| NF-κB signaling | IRAK4 | KT-474 | Phase I (ABC-DLBCL) | NCT04772885 |
| Ubiquitin proteasome system | CRBN | Lenalidomide | Phase II (+ DA-EPOCH-R, lymphoma including DLBCL) | NCT02213913 [292] |
| Phase II (+ R-CHOP, lymphoma including DLBCL) | NCT00670358 [293] | |||
| Phase II (+ R-CHOP21, lymphoma including DLBCL) | NCT00907348 [294] | |||
| Phase II (+ rituximab, lymphoma including DLBCL) | NCT00294632 [295] | |||
| Phase II (+ ibrutinib and rituximab, r/r DLBCL) | NCT02077166 [296] | |||
| Phase III (maintenance regiment, DLBCL) | NCT01122472 [297] | |||
| Proteasome | Bortezomib |
Approval for multiple myeloma, Phase III (NHL and DLBCL) |
||
| ixazomib |
Approval for multiple myeloma, Phase I/II (DLBCL) |
|||
| Proteasomal USP14 and UCHL5 deubiquitinases | b-AP15 | Preclinical (DLBCL) | [298] | |
| p53 signaling | p53 | Eprenetapopt (APR-246) | Phase II (Leukemia) | NCT03588078 |
| MDM2 | Idasanutlin (RG7388) | Phase III (+ Cytarabine, leukemia) | NCT02545283 | |
| XPO1 | XPO1 | Selinexor (KPT-330) | Approval for r/r DLBCL and r/r multiple myeloma | [299] |
| Proliferation | CDK4/6 | Palbociclib | Phase II (+ Ibrutinib for mantle cell lymphoma and B-cell lymphoma) | NCT03478514 |
| Abemaciclib | Phase II (MCL) | NCT01739309 | ||
| CDK9 | Dinaciclib | Phase Ib (+ Pembrolizumab for DLBCL) | NCT02684617 (Terminated); [234] | |
| Voruciclib | Phase I (DLBCL) | NCT03547115; [300] | ||
| CXCR4 | CXCR4 | PF-06747143 | Preclinical | [301] |
| CXCR4-directed auristatin E nanoconjugate | T22-AUR | Preclinical | [302] | |
| CXCR4 modified | CD19 CAR T cells | Phase I (refractory NHL) | NCT04684472 | |
| CXCR4-directed | radioligand therapy | Preclinical | [303] | |
| Immunotherapy | PD-1 | Nivolumab | Phase 1b (r/r DLBCL) | NCT01592370 [304] |
| Phase II (DLBCL, patients with relapse after or were ineligible for autologous hematopoietic cell transplantation) | NCT02038933 [305] | |||
| Pembrolizumab | Phase 1 (hematology malignancies including DLBCL) | NCT01953692 [306] | ||
| Preclinical (+ R-CHOP, in R-CHOP untreated DLBCL) | [307] |