13 research outputs found
A single center phase II study of ixazomib in patients with relapsed or refractory cutaneous or peripheral Tâcell lymphomas
The transcription factor GATAâ3, highly expressed in many cutaneous Tâcell lymphoma (CTCL) and peripheral Tâcell lymphomas (PTCL), confers resistance to chemotherapy in a cellâautonomous manner. As GATAâ3 is transcriptionally regulated by NFâÎșB, we sought to determine the extent to which proteasomal inhibition impairs NFâÎșB activation and GATAâ3 expression and cell viability in malignant T cells. Proteasome inhibition, NFâÎșB activity, GATAâ3 expression, and cell viability were examined in patientâderived cell lines and primary Tâcell lymphoma specimens ex vivo treated with the oral proteasome inhibitor ixazomib. Significant reductions in cell viability, NFâÎșB activation, and GATAâ3 expression were observed preclinically in ixazomibâtreated cells. Therefore, an investigatorâinitiated, singleâcenter, phase II study with this agent in patients with relapsed/refractory CTCL/PTCL was conducted. Concordant with our preclinical observations, a significant reduction in NFâÎșB activation and GATAâ3 expression was observed in an exceptional responder following one month of treatment with ixazomib. While ixazomib had limited activity in this small and heterogeneous cohort of patients, inhibition of the NFâÎșB/GATAâ3 axis in a single exceptional responder suggests that ixazomib may have utility in appropriately selected patients or in combination with other agents.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139920/1/ajh24895.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139920/2/ajh24895_am.pd
Survival following salvage therapy for primary refractory peripheral Tâcell lymphomas (PTCL)
Optimal salvage therapy for primary refractory peripheral Tâcell lymphomas (PTCL) and the role of hematopoietic stem cell transplant (SCT) remain poorly defined. We conducted a retrospective review of clinical outcomes and prognostic factors in a singleâcenter cohort of 93 patients with primary refractory PTCL, defined as progression during firstâline therapy or relapse within 6 months of its completion. Clinical outcomes were poor in this population, with median eventâfree survival (EFS) of 3.5 months, median overall survival (OS) of 9.1 months, and 34% 3âyear survival. Outcomes were comparable in patients who progressed through firstâline therapy and patients who achieved CR/PR and subsequently relapsed within 6 months. A majority exhibited highârisk features and had intermediate to high risk IPI, which correlated with inferior outcomes. There was no difference in outcomes between patients who received singleâagent salvage regimens and patients who underwent traditional, multiâagent salvage regimens. Thus, participation in wellâdesigned clinical trials should be encouraged in this population. Additionally, there may be a trend toward improved EFS and OS in patients who underwent autologous or allogeneic SCT compared to patients who achieved CR or PR but were not transplanted.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142498/1/ajh24992.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142498/2/ajh24992_am.pd