scholarly journals Anti-PD-1-Antibody (Tislelizumab) Combined with Deacetylase Inhibitor (Chidamide), Lenalidomide and Etoposide for the Treatment of Refractory/Relapsed Extranodal Natural Killer/T Cell Lymphoma, Nasal Type (r/r-ENKTL): Preliminary Results from a Prospective, Multicenter, Single -Arm, Phase II Trial

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1368-1368
Author(s):  
Lei Zhang ◽  
Xiyang Liu ◽  
Xinhua Wang ◽  
Yu Chang ◽  
Xiaorui Fu ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Natural Killer ◽  
Phase Ii ◽  
Response Rate ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Natural Killer T Cell ◽  
Preliminary Results ◽  
Killer T Cell

Abstract B ackground: Extranodal Natural Killer/T Cell Lymphoma(ENKTL) is a highly aggressive non-Hodgkin lymphoma (NHL), with higher incidence in Asia, which is related to Epstein-Barr virus (EBV) infection. Patients with r/r-ENKTL have a poor prognosis, and is lack of effective treatment. Anti-PD-1-Antibody plus Chidamide was effective and well tolerated on r/r-ENKTL (SCENT Trial, 2020 ASH). Lenalidomide is an immunomodulatory agent, previous studies showed activity in r/r-lymphoma with an acceptable safety. Etoposide is an important chemical agent in the treatment of ENKTL. Here we present preliminary results of Anti-PD-1 antibody combined with Chidamide, Lenalidomide and Etoposide for the r/r-ENKTL. Methods: This was a prospective, single-arm, open-label, multi-center, phase II clinical trial. This trial enrolled eligible patients with histologically confirmed r/r-ENKTL failing from at least 1-line treatment; ECOG performance status ≤ 2; adequate organ function and bone marrow function; and at least one measurable or evaluable lesion. Patients received 6 cycles of Tislelizumab (200mg), Chidamide (20mg q3d), Lenalidomide (25mg d1-10) and Etoposide (100mg/m 2 d1-3), every 21 days cycle. Then received 10 cycles of Tislelizumab (200mg) maintenance treatment, every 21 days cycle. The primary endpoints were objective response rate (ORR) based on Lugano 2014 criteria, duration of response (DOR), progression-free survival (PFS), overall survival (OS) and disease control rate (DCR). Secondary endpoints were median survival time (MST) and safety. Adverse events (AE) were rated according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) 5.0. This trial is registered at ClinicalTrials.gov (NCT04038411). R esults: From July 2020 to July 2021, 12 patients were screened and 10 eligible patients were enrolled, median age was 36.5 years (range 18-58), 8 (90.0%) male, 8(80.0%) patients with stage Ⅲ-Ⅳ of disease at screening, 4 (40.0%) patients received ≥2 lines of prior systemic therapy. Of 8 response evaluable patients, 7 (87.5%) achieved response including 5 (62.5%) patients with CR. The median time to initial response was 4.0 weeks (2-6 weeks). 10 Patients reported treatment-related AEs (TRAEs). The most frequently observed TRAEs were neutropenia (10 patients), thrombocytopenia (4 patients), transaminase increased (3 patients), nausea (4 patients). The most frequent Grade (G) ≥3 TRAEs were neutropenia (6 patients). Immune-related AEs were reported in 2 patients with G1 hypothyroidism. No death was related to the study. C onclusion: Tislelizumab combined with Chidamide, Lenalidomide and Etoposide regimen have a very high response rate in r/r-ENKTL for the first time, and the safety is under control. It is a promising therapeutic option for this population, further investigation is warranted. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Combination of anti-PD-1 antibody with P-GEMOX as a potentially effective immunochemotherapy for advanced natural killer/T cell lymphoma

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Jun Cai ◽  
Panpan Liu ◽  
Huiqiang Huang ◽  
Yajun Li ◽  
Shuyun Ma ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Genetic Alterations ◽  
T Cell Lymphoma ◽  
Natural Killer T Cell ◽  
Programmed Death ◽  
Killer T Cell ◽  
Natural Killer T

AbstractAdvanced natural killer/T cell lymphoma (NKTL) has demonstrated poor prognosis with currently available therapies. Here, we report the efficacy of anti-programmed death 1 (PD-1) antibody with the P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) regimen in advanced NKTL. Nine patients underwent six 21-day cycles of anti-PD-1 antibody (day 1), pegaspargase 2000 U/m2 (day 1), gemcitabine 1 g/m2 (days 1 and 8) and oxaliplatin 130 mg/m2 (day 1), followed by anti-PD-1 antibody maintenance every 3 weeks. Programmed death-ligand 1 (PD-L1) expression and genetic alterations were determined in paraffin-embedded pretreatment tissue samples using immunohistochemistry and next-generation sequencing (NGS) analysis. Responses were assessed using 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) and computed tomography or magnetic resonance imaging. Eight patients exhibited significant responses, comprising of seven complete remissions and one partial remission (overall response rate: 88.9%). After a median follow-up of 10.6 months, 6/9 patients (66.7%) remained in complete remission. The most common grade 3/4 adverse events were anemia (33.3%), neutropenia (33.3%), and thrombocytopenia (33.3%); all of which were manageable and resolved. Immunochemotherapy produced a high response rate in patients with positive PD-L1 expression (5/6, 83.3%). NGS analysis suggested that STAT3/JAK3/PD-L1 alterations and ARID1A mutation were associated with immunochemotherapy efficacy. Mutation in DDX3X and alteration in epigenetic modifiers of KMT2D, TET2, and BCORL1 might indicate a poor response to immunochemotherapy. In conclusion, the anti-PD-1 antibody plus P-GEMOX regimen demonstrated promising efficacy in advanced NKTL. PD-L1 expression combined with specific genetic alterations could be used as potential biomarkers to predict therapeutic responses to immunochemotherapy.

Natural killer T-cell lymphoma causing bilateral recurrent recalcitrant dacryocystitis

Orbit ◽  
2021 ◽  
pp. 1-5
Author(s):  
Elzbieta Mechel ◽  
Ann. Q. Tran ◽  
Victoria S. North ◽  
Farnoush M. Moen ◽  
Andrea A. Tooley
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Natural Killer T Cell ◽  
Killer T Cell ◽  
Natural Killer T

scholarly journals Daratumumab monotherapy for patients with relapsed or refractory natural killer/T-cell lymphoma, nasal type: an open-label, single-arm, multicenter, phase 2 study

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Huiqiang Huang ◽  
Jun Zhu ◽  
Ming Yao ◽  
Tae Min Kim ◽  
Dok Hyun Yoon ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Phase 2 ◽  
Nasal Type ◽  
Natural Killer T Cell ◽  
Phase 2 Study ◽  
Duration Of Response ◽  
Killer T Cell

Abstract Background Natural killer/T-cell lymphoma (NKTCL) is a disease with limited treatment options and poor outcomes. Daratumumab monotherapy demonstrated clinical activity in a single-patient case report. We present data from the primary analysis of a phase 2 study of daratumumab monotherapy in relapsed or refractory (R/R) NKTCL. Methods This phase 2 study with Simon’s two-stage design evaluated daratumumab in patients with histologically confirmed extranodal NKTCL, nasal type, per WHO classification that was refractory to or relapsed after ≥ 1 line of chemotherapy, who were not candidates for other treatment modalities. All patients received daratumumab 16 mg/kg intravenously once weekly for Cycles 1 and 2, every other week for Cycles 3 through 6, and every 4 weeks thereafter until progression or unacceptable toxicity; all cycles were 28 days. The primary end point was objective response rate (ORR) based on blinded independent central review per Revised Criteria for Response Assessment of Hodgkin and non-Hodgkin Lymphoma (Lugano classification). Results In total, 32 Asian patients received daratumumab. The ORR was 25.0% (95% confidence interval [CI] 11.5–43.4); all 8 responders had a partial response; and the median duration of response was 55.0 days (95% CI 29–339). At 10.2 months of median follow-up, median progression-free survival (PFS) was 53.0 days (95% CI 43–106); the 4-month PFS rate was 13.0%. Median overall survival (OS) was 141.0 days (95% CI 94–438); the 6-month OS rate was 42.9%. Nineteen (59.4%) patients had grade 3/4 treatment-emergent adverse events (TEAEs); the most common was thrombocytopenia (25.0%; n = 8). TEAEs leading to death occurred in 4 patients (death, respiratory failure, septic shock, and pneumonia); all were unrelated to daratumumab. Conclusions In patients with R/R NKTCL, daratumumab monotherapy was well tolerated with no new safety concerns and achieved an ORR of 25.0%. However, no patients achieved complete response, and duration of response was short. Trial registration ClinicalTrials.gov, NCT02927925. Registered 7 October 2016.

Sign in / Sign up

Export Citation Format

Share Document