Review Article
Novel Therapies for Aggressive B-Cell Lymphoma
Table 6
Kinase inhibitors currently in clinical development for the treatment of aggressive NHL. [CDK: cyclin-dependant kinase; CLL: chronic lymphocytic leukemia; CR: complete response; DLBCL: diffuse large B-cell lymphoma; ERK: extracellular signal regulated kinase; FFP: freedom from progression; FL: follicular lymphoma; HL: Hodgkin lymphoma; JAK: Janus kinase; MCL: mantle cell lymphoma; mPFS: median progression-free survival; NHL: non-Hodgkin lymphoma; MEK: mitogen-activated protein kinase kinase; MM: multiple myeloma; mTOR: mammalian target of rapamycin; ORR: overall response rate; OS: overall survival; PDGF: platelet-derived growth factor; PDGFR: platelet-derived growth factor receptor; PFS: progression-free survival; PR: partial response; R/R: relapsed or refractory; RTK: receptor tyrosine kinase; SD: stable disease; SLL: small lymphocytic lymphoma; TKI: tyrosine kinase inhibitor; VEGFR: vascular endothelial growth factor receptor.]
| | Drug | MOA (target) | Eligibility | Phase | Randomized | Results |
| | Dinaciclib [183] | CDK1, 2, 5, 9 inhibitor | R/R in low-grade lymphoma and DLBCL | I | No | PR: DLBCL: 1/7; SD: FL: 2/7; MCL: 1/1 | | Fostamatinib [198] | Syk inhibitor | R/R B-cell NHL and CLL | I/II | No | ORR: DLBCL: 22%; FL: 10% SLL/CLL: 55% in SLL/CLL: MCL: 11%; overall mPFS: 4.2 months | | Dasatinib [202] | RTK inhibitor of BCR-ABL, SRC, c-Kit, PDGF and ephrin receptor kinases | R/R NHL | I/II | No | ORR: 32%; 2-year PFS: 13%; 2-year OS: 50% | | Enzastaurin [201] | Protein kinase beta inhibitor | R/R DLBCL | II | No | FFP: 22% | | PCI-32765 [204] | Bruton’s tyrosine kinase inhibitor | R/R B-cell NHL | I | Dose-finding | ORR: 43% | | SB1518 [208] | JAK2 inhibitor | R/R lymphoma | I | Dose-finding | PR: 3/26 (2 in MCL) | | Sorafenib [221] | TKI inhibitor of RAF/MEK/ERK/c-kit/Flt3, VEGFRs, PDGFRs, RET | R/R NHL | II | No | ORR: 10%; CR: 5% | | Sorafenib [222] | TKI inhibitor of RAF/MEK/ERK/c-kit/Flt3, VEGFRs, PDGFRs, RET | R/R lymphoma (with Akt inhibitor perifosine) | II | No | ORR: 23% (all PR; all in HL) | | Sorafenib [223] | TKI inhibitor of RAF/MEK/ERK/c-kit/Flt3, VEGFRs, PDGFRs, RET | R/R MM or lymphoma (with mTOR inhibitor everolimus) | I/II | Dose-finding | ORR: 33% |
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