Clinical features and treatment outcomes of primary ocular adnexal mucosa-associated lymphoid tissue lymphoma: a single center retrospective analysis of 64 patients in China

AIM: To investigate the clinical features, treatment and prognosis of primary ocular adnexal mucosa-associated lymphoid tissue lymphoma(POAML).METHODS: A retrospective analysis was performed on 64 patients with POAML who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2006 to December 2018.RESULTS: With a median follow-up of 61 mo(range, 2-156 mo), estimated overall survival(OS) rate and progressionfree survival(PFS) rate at 10 y reached 94.5% and 61.5%, respectively. Median OS time and PFS time were not reached. During this period, only 3 patients died, but none of them died directly due to disease progression. One patient(1.6%) developed transformation to diffuse large B-cell lymphoma(DLBCL). Of the 56 patients achieved complete remission after first-line treatment, 5(8.9%) developed local and/or systemic relapse eventually. Patients ≥60 y had significantly shorter PFS than younger patients(P=0.01). For patients with early stages(Ann Arbor stage I and stage II), univariate analysis confirmed that radiotherapydose lower than 32 Gy were independently associated with shorter PFS(P=0.04). Other factors including gender, bone marrow involvement, the initial location of the disease, and the laterality were not associated with PFS.CONCLUSION: The data from our center indicate that POAML has a slow clinical progression and has an excellent clinical outcome. Patients with POAML harbor a continual risk of relaps and transformation to aggressive subtype of lymphoma.

The combination of chidamide with the CHOEP regimen in previously untreated patients with peripheral T-cell lymphoma: a prospective, multicenter, single arm, phase 1b/2 study

Objective:To assess the efficacy and safety of the novel histone deacetylase inhibitor,chidamide,in combination with cyclophosphamide,doxorubicin,vincristine,etoposide,and prednisone(Chi-CHOEP)for untreated peripheral T-cell lymphoma(PTCL).Methods:A prospective,multicenter,single arm,phase 1 b/2 study was conducted.A total of 128 patients with untreated PTCL(18–70 years of age)were enrolled between March 2016 and November 2019,and treated with up to 6 cycles with the Chi-CHOEP regimen.In the phase 1 b study,3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximumtolerated dose and recommended phase 2 dose(RP2 D).The primary endpoint of the phase 2 study was 2-year progression-free survival(PFS).Results:Fifteen patients were enrolled in the phase 1 b study and the RP2 D for chidamide was determined to be 20 mg,twice a week.A total of 113 patients were treated at the RP2 D in the phase 2 study,and the overall response rate was 60.2%,with a complete response rate of 40.7%.At a median follow-up of 36 months,the median PFS was 10.7 months,with 1-,2-,and 3-year PFS rates of 49.9%,38.0%,and 32.8%,respectively.The Chi-CHOEP regimen was well-tolerated,with grade 3/4 neutropenia occurring in approximately two-thirds of the patients.No unexpected adverse events(AEs)were reported and the observed AEs were manageable.Conclusions:This large cohort phase 1 b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.

Updating targets for natural killer/T-cell lymphoma immunotherapy

Natural killer/T-cell lymphoma(NKTCL)is a highly invasive subtype of non-Hodgkin lymphoma,typically positive for cytoplasmic CD3,CD56,cytotoxic markers,including granzyme B and TIA1,and Epstein-Barr virus(EBV).The current treatment methods for NKTCL are associated with several drawbacks.For example,chemotherapy can lead to drug resistance,while treatment with radiotherapy alone is inadequate and results in frequent relapses.Moreover,hematopoietic stem cell transplantation exhibits limited efficacy and is not well recognized by domestic and foreign experts.In recent years,immunotherapy has shown good clinical results and has become a hot spot in cancer research.Clinical activity of targeted antibodies,such as daratumumab(anti-CD38 antibody)and brentuximab vedotin(anti-CD30 antibody),have been reported in NKTCL.Additionally,dacetuzumab and Campath-1 H have demonstrated promising results.Further encouraging data have been obtained using checkpoint inhibitors.The success of these immunotherapy agents is attributed to high expression levels of programmed death-ligand 1 in NKTCL.Furthermore,anti-CCR4 monoclonal antibodies(m Abs)exert cytotoxic actions on both CCR4+tumor cells and regulatory T cells.Depletion of these cells and the long half-life of anti-CCR4 m Abs result in enhanced induction of antitumor effector T cells.The role of IL10 in NKTCL has also been investigated.It has been proposed that exploitation of this cytokine might provide potential novel therapeutic strategies.Cellular immunotherapy with engineered cytotoxic T lymphocytes targeted against LMP1 and LMP2 has shown promising results and sustained remission.Cellular immunotherapy may be used either as maintenance therapy following initial induction chemotherapy or in cases of relapsed/refractory disease.The present review outlines the known immunotherapy targets for the treatment of NKTCL.