Cost-effectiveness of obinutuzumab plus bendamustine in Chinese patients with relapse and refractory follicular lymphoma.

A decision analytic model was constructed to assess the cost-effectiveness of obinutuzumab plus bendamustine followed by obinutuzumab maintenance therapy (O-B-O) in Chinese patients with relapsed and refractory follicular lymphoma (rrFL). O-B-O was associated with a dominant or more favorable cost-effectiveness than the conventional therapies. Survival outcomes, quality of life of progression-free survival, and subsequent treatment costs for progressive disease were the main drivers of the cost-effectiveness of O-B-O. The cost-effectiveness proportions of O-B-O relative to conventional therapies under the recommended cost-effectiveness threshold ranged from 61.0% to 99.9%. Thus, O-B-O was highly cost-effective for treating patients with rrFL in China compared with conventional therapies.

Chinese expert consensus on Bruton tyrosine kinase inhibitors in the treatment of B-cell malignancies.

Targeted therapy with Bruton tyrosine kinase (BTK) inhibitors have revolutionized the treatment of patients with various B-cell malignancies. BTK inhibitors such as ibrutinib, zanubrutinib, orelabrutinib, and acalabrutinib have shown good clinical efficacy and better safety profiles than those of traditional chemotherapy and chemoimmunotherapy regimens. Multiple studies on new BTK inhibitors are ongoing, which may provide more therapeutic options for the treatment of B-cell malignancies. Considering the unmet need of evidence on BTK inhibitors in all clinical settings and to standardize the use of BTK inhibitors available in mainland China, Taiwan, Hong Kong, and Macau regions, this consensus has been formulated for the treatment of various B-cell malignancies based on the clinical practice and available evidences on the use of BTK inhibitors. The recommendations of this consensus will provide guidance to physicians and clinical researchers on the effective treatment of B-cell malignancies with BTK inhibitors.

Burden of lymphoma in China, 1990-2019: an analysis of the global burden of diseases, injuries, and risk factors study 2019.

BACKGROUND: China is facing an aggravating disease burden of lymphoma. However, accurate information about lymphoma burden at the national and provincial levels is limited. RESULTS: The estimated number of disability-adjusted life years were 86,171.85 for Hodgkin lymphoma and 1,306,247.77 for non-Hodgkin lymphoma with the age-standardized rates of 4.95 and 71.00, respectively, per 100,000 population. There were estimated 9,468 new cases and 2,709 Hodgkin lymphoma-related deaths, and 91,954 new cases and 44,310 non-Hodgkin lymphoma-related deaths. Older individuals had a higher lymphoma burden. The age-standardized disability-adjusted life year rate in men was approximately two-folds higher than that in women. Moreover, disparities in lymphoma burden were observed across the provinces. Between 1990 and 2019, the disability-adjusted life year number decreased by 57.8% for Hodgkin lymphoma, and increased by 100.9% for non-Hodgkin lymphoma. CONCLUSION: Burden of lymphoma showed heterogeneous change patterns varied according to sex, age, and provinces, with a steady decrease in Hodgkin lymphoma and a significant increase in non-Hodgkin lymphoma during the past three decades. METHODS: Following the analytical strategy used in the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, age-, sex-, and province-specific incidence, mortality, and prevalence of Hodgkin lymphoma and non-Hodgkin lymphoma were analyzed. Lymphoma burden was assessed by incidence, mortality, prevalence, and disability-adjusted life year.

A Multi-Center, Real-World Study of Chidamide for Patients With Relapsed or Refractory Peripheral T-Cell Lymphomas in China.

Chidamide has demonstrated significant clinical benefits for patients with relapsed/refractory (R/R) PTCL in previous studies. This multi-center observational study was aimed to evaluate the objective response rate (ORR), overall survival (OS), and safety of chidamide. From February 2015 to December 2017, 548 patients with R/R PTCL from 186 research centers in China were included in the study. Among the 261 patients treated with chidamide monotherapy, ORR was 58.6% and 55 patients (21.1%) achieved complete response (CR). Among the 287 patients receiving chidamide-containing combination therapies, ORR was 73.2% and 73 patients (25.4%) achieved CR. The median OS of all patients was 15.1 months. The median OS of patients receiving chidamide monotherapy and combination therapies was 433 and 463 days, respectively. These results demonstrate a significant survival advantage of chidamide treatments as compared with international historical records. Common adverse effects (AEs) were hematological toxicities. Most AEs in both monotherapy and combined treatments were grade 1-2. No unanticipated AEs occurred. In conclusion, chidamide-based therapy led to a favorable efficacy and survival benefit for R/R PTCL. Future studies should explore the potential advantage of chidamide treatment combined with chemotherapy.

LINC00265/miR-4500 Axis Accelerates Acute Lymphoblastic Leukemia Progression by Enhancing STAT3 Signals.

BACKGROUND: Long noncoding RNA LINC00265 or miR-4500 is involved in the pathogenesis of many cancers. However, their functions in acute lymphoblastic leukemia (ALL) remain unknown. In this study, we investigated how LINC00265 and miR-4500 regulate the malignant characteristics of ALL. METHODS: Real-time PCR was used in examining the expression of LINC00265 in ALL cell lines and blood of patients with ALL. Cell proliferation, cell migration, and xenograft tumor assays were performed to verify the function of LINC00265 subjected to overexpressing and silencing experiments. The ceRNA mechanism with LINC00265/miR-4500/STAT3 was investigated through luciferase and RNA pull-down assays. Finally, the function of the LINC00265/miR-4500/STAT3 axis subjected to overexpressing and silencing assays was determined through cell proliferation, cell migration, and xenograft tumor assays. RESULTS: LINC00265 was highly expressed in ALL cell lines and blood of patients with ALL and facilitated the proliferation, migration, invasion, and growth of xenograft tumors of ALL cells. The silencing of LINC00265 expression with LINC00265 siRNA significantly inhibited the malignancy of the ALL cells. RNA pull-down and luciferase assays demonstrated that LINC00265 competitively targeted miR-4500 and enhanced STAT3 expression. Furthermore, miR-4500 inhibitors or overexpressed LINC00265 up-regulated STAT3 expression, and miR-4500 mimics or STAT3 shRNAs eliminated the LINC00265-induced malignancy of the ALL cells. CONCLUSION: Mechanistically, LncRNA LINC00265 can competitively interact with miR-4500 and thereby up-regulates STAT3 signaling and enhances the malignancy of tumors.

Ibrutinib in combination with rituximab in relapsed or refractory mantle cell lymphoma: a single-centre, open-label, phase 2 trial.

BACKGROUND: Ibrutinib is approved in the EU, USA, and other countries for patients with mantle cell lymphoma who received one previous therapy. In a previous phase 2 study with single-agent ibrutinib, the proportion of patients who achieved an objective response was 68%; 38 (34%) of 111 patients had transient lymphocytosis. We hypothesised that adding rituximab could target mantle cell lymphoma cells associated with redistribution lymphocytosis, leading to more potent antitumour activity. METHODS: Patients with a confirmed mantle cell lymphoma diagnosis (based on CD20-positive and cyclin D1-positive cells in tissue biopsy specimens), no upper limit on the number of previous treatments received, and an Eastern Cooperative Oncology Group performance status score of 2 or less were enrolled in this single-centre, open-label, phase 2 study. Patients received continuous oral ibrutinib (560 mg) daily until progressive disease or unacceptable toxic effects. Rituximab 375 mg/m(2) was given intravenously once per week for 4 weeks during cycle 1, then on day 1 of cycles 3-8, and thereafter once every other cycle up to 2 years. The primary endpoint was the proportion of patients who achieved an objective response in the intention-to-treat population and safety assessed in the as-treated population. The study is registered with ClinicalTrials.gov, number NCT01880567, and is still ongoing, but no longer accruing patients. FINDINGS: Between July 15, 2013, and June 30, 2014, 50 patients were enrolled. Median age was 67 years (range 45-86), and the median number of previous regimens was three (range 1-9). At a median follow-up of 16·5 months (IQR 12·09-19·28), 44 (88%, 95% CI 75·7-95·5) patients achieved an objective response, with 22 (44%, 30·0-58·7) patients achieving a complete response, and 22 (44%, 30·0-58·7) a partial response. The only grade 3 adverse event in >=10% of patients was atrial fibrillation, which was noted in six (12%) patients. Grade 4 diarrhoea and neutropenia occurred in one patient each. Adverse events led to discontinuation of therapy in five (10%) patients (atrial fibrillation in three [6%] patients, liver infection in one [2%], and bleeding in one [2%]). Two patients died while on-study from cardiac arrest and septic shock; the latter was deemed possibly related to treatment. INTERPRETATION: Ibrutinib combined with rituximab is active and well tolerated in patients with relapsed or refractory mantle cell lymphoma. Our results provide preliminary evidence for the activity of this combination in clinical practice. A phase 3 trial is warranted for more definitive data. FUNDING: Pharmacyclics LLC, an AbbVie Company.

[A prospective, multi-centre clinical trial to evaluate the early clinical efficacy and safety of a generic imatinib in treating patients with chronic phase of chronic myelogenous leukemia].

OBJECTIVE: To evaluate the early hematologic, cytogenetic and molecular responses in newly diagnosed patients with chronic myelogenous leukemia in chronic phase（CML-CP）and initially treated with a generic imatinib（Xinwei）, manufactured by Jiansu Hansoh Pharmaceutical Group Co., Ltd. METHODS: 107 newly diagnosed patients of CML-CP, whose ages were above 18- year- old and who had never received any tyrosine kinase inhibitor（TKI）were treated with Xinwei 400 mg QD. The hematologic, cytogenetic and molecular responses were assessed at 3- and 6-month, and adverse effects were evaluated throughout the study. RESULTS: 107 patients were treated with Xinwei for at least 3 months, 54 of them were treated for 6 months or more. At 3- month, the complete hematologic responses（CHR）rate were 98.1%（105/107）; 47/57（82.5%） patients achieved major cytogenetic response（MCyR）, and 20/57 （35.1%） patients complete cytogenetic response（CCyR）; BCR- ABLIS was ≤10% in 77/106 patients （72.6%）, 11 of them（10.4%）achieved major molecular response（MMR, BCR-ABLIS was ≤0.1%）. At 6-month, the CHR rate was 100%（54/54）; 28/39 patients（71.8%）achieved CCyR; BCR-ABLIS was ≤1% in 37/54 patients （68.5% ）, 18 of them （33.3% ） achieved MMR. The grade Ⅲ leukopenia, thrombocytopenia and anemia rates were 19.5%, 23.0% and 13.8%, respectively. No grade Ⅳ hematologic toxicity occurred. The common non- hematologic toxicities were edema（74.7%）, nausea（48.3%）, bone pain（42.5%）, rash（36.8%）, diarrhea（34.5%）, fever（23.0%）, cramp（11.5%）and impaired liver function （3.4%）. No patient experienced grade Ⅳ non- hematologic toxicity. No adverse effects related death occurred. CONCLUSION: Our results revealed the excellent early haematology, cytogenetic and molecular responses and safety of Xinwei in treating patients with CML-CP.

Effect of a nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester on invasion of human colorectal cancer cell line SL-174T.

AIM: To investigate the effect and mechanism of action of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on invasion and metastasis of human colorectal cancer cell line SL-174T. METHODS: Human colorectal cancer cell line SL-174T was cultured and treated separately with four different dosages of L-NAME for 72 h. Nitric oxide (NO) production was measured with Griess reagent. The effect of L-NAME on invasion and migration of SL-174T cells were evaluated by using Transwell chambers attached with polycarbonate filters and reconstituted basement membrane (Matrigel). RT-PCR was performed to determine the mRNA levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor metalloproteinase-2 (TIMP-2). RESULTS: L-NAME could significantly inhibit NO production of SL-174T in a dose-dependent manner. After being treated for 72 h with 0.2, 0.4, 0.8, and 1.0 mmol/L L-NAME, respectively, the ability of the L-NAME treated SL-174T cells to invade the reconstituted basement membrane decreased significantly (t = 8.056, P< 0.05; t = 14.467, P< 0.01; t = 27.785, P< 0.01; and t = 29.405, P< 0.01, respectively) and the inhibition rates were 10.29%, 19.62%, 34.08%, and 42.23%, respectively. Moreover, L-NAME could inhibit migration of SL-174T cells, and the inhibition rates were 20.76%, 24.95%, 39.43%, and 46.85% for L-NAME at 0.2, 0.4, 0.8, and 1.0 mmol/L, respectively (t= 15.116, P< 0.01). In addition, after treatment with L-NAME, expression of MMP-2 mRNA was significantly decreased (t = 71.238, P< 0.01) and that of TIMP-2 mRNA was markedly increased (t = -13.020, P< 0.01). CONCLUSION: L-NAME exerts anti-invasive and anti-metastatic effects on SL-174T cell line via downregulating MMP-2 mRNA expression and upregulating TIMP-2 mRNA expression.