Abstract
Background:Chidamide is an orally bioavailable benzamide class of histone deacetylase inhibitor (HDACi), that selectively inhibits activity of HDAC1, 2, 3 and 10. It was approved by the Chinese FDA for relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL) with a recommended dose of 30 mg twice weekly (BIW). However, the efficacy and safety of Chidamide remain to be determined in relapsed or refractory extranodal natural killer T-cell lymphoma (ENKTCL), and the optimal dosing schedule was unclear. The purpose of the current study were to evaluate the clinical response and toxicity for R/R-ENKTCL at two dosing schedule of Chidamide monotherapy.
Methods:This is an open-label, prospective phase II trial in China. Inclusion criteria included histologically confirmed ENKTCL, disease progression or non-response after asparaginase-based chemotherapy. Chidamide 30mg BIW or 10mg daily was taken at least 6 weeks until disease progression or the occurrence of unacceptable toxicity. Utility of PET-CT in the therapeutic evaluation was employed. Serum EBV-DNA was monitored weekly. At the time of this abstract submission, the trial is still ongoing.
Results: A total of 15 relapsed or refractory ENKTCL patients failed to asparaginase-based chemotherapy or autologous hematopoietic stem cell transplantation (ASCT) were enrolled in this study (10mg QD group, n=9 and 30mg BIW group, n=6, respectively). Median previous chemotherapy regimens was 3(2-5), 2 patient relapsed following ASCT. 12 patients were evaluable for response and 3 patients still under treatment less than 6 weeks. ORR was 50.0% (6/12) with CR rate 33.3 %( 4/12) . Three patients got CR in 30mg group, one patient got CR in 10mg group (table1,figure 1). The median time to response was 5.9 (1.1 to 8.1) weeks. Median follow-up time was 3.7 months (0.8-11.5) so far. All four CR patients were still in disease-free more than 6.9 months (6.9-10.5). Serum EBV-DNA load during the course of treatment was declined or stable in all responders only two cases with elevated EBV-DNA level observed due to disease progression (figure 2). Most adverse events (AEs) were grade 1 or 2, and AEs ≥grade 3 hematologic toxicity were similar in both groups included neutropenia (50.0% vs. 44.4%) and thrombocytopenia (33.3% vs. 33.3%). 30mg group experienced a higher incidence of nausea and vomiting(100% vs. 44.4%). Meanwhile, we also treated six refractory B cell lymphoma patients, including three diffused large B cell lymphoma (DLBCL), two mantle cell lymphoma (MCL) and one follicular lymphoma. One DLBCL patient and one MCL patient obtained PR respectively.
Conclusions: Our study suggested that Chidamide was effective as single agent in the treatment of relapsed or refractory malignant lymphoma.. The therapeutic outcome for previous heavily-treated ENKTCL was encouraged without clinical EBV reactivation. It is too early to draw conclusions of response difference between two dosing schedule. Further clinical trial warranted.
( ClinicalTrials.gov, NCT 2878278 )
Disclosures: No relevant conflicts of interest to declare.
No relevant conflicts of interest to declare.
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