Ethnicity and socio-economic status affects the incidence and survival of hepatosplenic T-cell lymphoma

To address the lack of contemporary population-based epidemiological studies of hepatosplenic T-cell lymphoma (HSTCL), we undertook a population-based study of ICD-O-3-coded HSTCL in England. We used the National Cancer Registration Dataset and linked datasets on hospital admissions, Systemic Anti-Cancer Therapy, socio-demographics, comorbidities and death, identifying cases from 1 January 2013 to 31 December 2019 with survival data up to 5 January 2021. Crude and directly age-standardised incidence rates per million persons per year were calculated. Crude and adjusted incidence rate ratios compared incidence between groups using Poisson regression. A Cox proportional hazards model estimated mortality risks adjusted for age, sex, ethnicity, deprivation and allogenic stem cell transplant (allo-SCT; time varying). We identified 44 patients, mean age 42 years. Median survival was 11 months, and 1 and 5 year survivals were 48% (95% CI 29%–43%) and 22% (95% CI 12%–42%) respectively. The age-standardised incidence was 0.1 per million/year. Incidence was higher in areas with greater deprivation (0.15 per million/year), and more cases than expected were in non-White patients (39%). Non-Whites had a twofold increased risk of death (adjusted hazard ratio 2.21 [95% CI 1.03–4.78]) even after adjusting for deprivation, younger age and allo-SCT. In conclusion, ethnicity and socio-economic status affect both the incidence and survival of HSTCL

The safety and clinical effectiveness of rapid infusion with CT-P10 in patients with non-Hodgkin's lymphoma or chronic lymphocytic leukemia: A retrospective non-interventional post-authorization safety study in Europe

Rapid infusion (RI) of the rituximab biosimilar CT-P10 is currently only an approved treatment regimen for the treatment of rheumatoid arthritis. Although both CT-P10 and reference rituximab are known to be frequently administered using a RI regimen (≤90 min) in clinical practice, published data on the safety of RI of CT-P10 in patients with NHL and CLL are limited. Hence, this study collected real-world safety and effectiveness data on RI-CT-P10 from the medical records of 196 patients with NHL or CLL in 10 European centers, 6 months after the date of the first RI (index date); the infusion-related reaction (IRR) rate was compared to previously published data. Ten percent (95% confidence interval 6%–15%; n = 20/196) of patients experienced an infusion-related reaction (IRR) on day 1–2 post-index, which was not significantly different (p = 0.45) to the IRR rate for rituximab described in a previous meta-analysis (8.8%). During the observation period, 2% of patients experienced grade 3–5 IRRs and 85% (n = 166) experienced an adverse event (non-IRR). The most common reason for discontinuation of first-line CT-P10 was planned treatment completion (81%; n = 158). Complete response and partial response to CT-P10 was observed in 74% (n = 142/192) and 22% (n = 42/192) of patients, respectively. The results of this real-world study demonstrate that the safety and effectiveness profile of RI-CT-P10 is similar to RI of reference rituximab and therefore support the current use of RI-CT-P10 in patients with NHL and CLL

Infection-related morbidity and mortality among older patients with DLBCL treated with full- or attenuated-dose R-CHOP

Infection-related morbidity and mortality are increased in older patients with diffuse large B-cell lymphoma (DLBCL) compared with population-matched controls. Key predictive factors for infection-related hospitalization during treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and deaths as a result of infection in older patients during and after treatment with R-CHOP remain incompletely understood. For this study, 690 consecutively treated patients age 70 years or older who received full-dose or attenuated-dose R-CHOP treatment were analyzed for risk of infection-related hospitalization and infection-related death. Median age was 77 years, and 34.4% were 80 years old or older. Median follow-up was 2.8 years (range, 0.4-8.9 years). Patient and baseline disease characteristics were assessed in addition to intended dose intensity (IDI). Of all patients, 72% were not hospitalized with infection. In 331 patients receiving an IDI ≥80%, 33% were hospitalized with ≥1 infections compared with 23.3% of 355 patients receiving an IDI of 80% across the whole cohort. Primary quinolone prophylaxis independently reduced infection-related admission. A total of 51 patients died as a result of infection. The 6-month, 12-month, 2-year, and 5-year cumulative incidences of infection-related death were 3.3%, 5.0%, 7.2%, and 11.1%, respectively. Key independent factors associated with infection-related death were an International Prognostic Index (IPI) score of 3 to 5, Cumulative Illness Rating Scale for Geriatrics (CIRS-G) score ≥6, and low albumin, which enabled us to generate a predictive risk score. We defined a smaller group (15%) of patients (IPI score of 0-2, albumin >36 g/L, CIRS-G score <6) in which no cases of infection-related deaths occurred at 5 years of follow-up. Whether patients at higher risk of infection-related death could be targeted with enhanced antimicrobial prophylaxis remains unknown and will require a randomized trial

Histone deacetylase inhibitor induces DNA damage, which normal but not transformed cells can repair

Histone deacetylase inhibitors (HDACi) developed as anti-cancer agents have a high degree of selectivity for killing cancer cells. HDACi induce acetylation of histones and nonhistone proteins, which affect gene expression, cell cycle progression, cell migration, and cell death. The mechanism of the tumor selective action of HDACi is unclear. Here, we show that the HDACi, vorinostat (Suberoylanilide hydroxamic acid, SAHA), induces DNA double-strand breaks (DSBs) in normal (HFS) and cancer (LNCaP, A549) cells. Normal cells in contrast to cancer cells repair the DSBs despite continued culture with vorinostat. In transformed cells, phosphorylated H2AX (γH2AX), a marker of DNA DSBs, levels increased with continued culture with vorinostat, whereas in normal cells, this marker decreased with time. Vorinostat induced the accumulation of acetylated histones within 30 min, which could alter chromatin structure-exposing DNA to damage. After a 24-h culture of cells with vorinostat, and reculture without the HDACi, γH2AX was undetectable by 2 h in normal cells, while persisting in transformed cells for the duration of culture. Further, we found that vorinostat suppressed DNA DSB repair proteins, e.g., RAD50, MRE11, in cancer but not normal cells. Thus, the HDACi, vorinostat, induces DNA damage which normal but not cancer cells can repair. This DNA damage is associated with cancer cell death. These findings can explain, in part, the selectivity of vorinostat in causing cancer cell death at concentrations that cause little or no normal cell death

Temporal trends in the incidence of haemophagocytic lymphohistiocytosis: a nationwide cohort study from England 2003-2018

Background Haemophagocytic lymphohistiocytosis (HLH) is rare, results in high mortality and is increasingly being diagnosed. Little is known about what is driving the apparent rise in the incidence of this disease.Methods Using national linked electronic health data from hospital admissions and death certification cases of HLH that were diagnosed in England between 1/1/2003 and 31/12/2018 were identified using a previously validated approach. We calculated incidence rates of diagnosed HLH per million population using mid-year population estimates by calendar year, age group, sex and associated comorbidity (haematological malignancy, inflammatory rheumatological or bowel diseases (IBD)) associated with the diagnosis of HLH. We modelled trends in incidence and the interactions between calendar year, age and associated comorbidity using Poisson regression.Findings There were 1674 people with HLH diagnosed in England between 2003 and 2018. The incidence rate quadrupled (Incidence Rate Ratio (IRR) 2018 compared to 2003: 3.88 95% Confidence Interval (CI) 2.91 to 5.28), increasing 11% annually (adjusted IRR 1.11 95% CI 1.09 to 1.12). There was a rising trend in all age groups except those aged less than 5 years. There was a transition across the age groups with greater increases in those aged 5 to 14 years of HLH associated with rheumatological disease/IBD compared to HLH associated with haematological malignancy, with similar increases in HLH associated with both co-morbidities for those 15-54, and greater increases in associated haematological malignancies for those 55 years and older.Interpretation The incidence of HLH in England has quadrupled between 2003 and 2018, increasing 11% annually. Substantial variation in the incidence occurred by age group and by HLH associated comorbidities with inflammatory rheumatological diseases or IBD associated HLH increasing more among the young and middle age groups, whereas in older age groups the largest increase was seen with haematological malignancy-associated HLH.Evidence before this study There is a paucity of population-based data on the epidemiology of HLH worldwide. The available evidence relies mostly upon a collection of cases series published in The Lancet in 2014 which described 2197 cases of HLH in adults reported in the literature to that point. Almost all of these were from tertiary referral specialist centres and/or described in small case series. The incidence of HLH has only been described in a few reports – and mainly this has focused on children with primary HLH. No previous studies have been large enough to examine trends in incidence by age, sex, underlying risk factors and calendar time.Added value of this study This study quantifies the incidence of diagnosed HLH for the first time in a nationwide manner for all age groups. It reports on 1674 patients with HLH from England and shows that there is substantial variation in the incidence by age group, associated disease and calendar time. The results imply reasons for the increase in HLH could be related to the increasing occurrence of haematological cancer, inflammatory rheumatological or bowel diseases and the treatments given for these conditions. This study has been carried out in partnership with the National Congenital Anomalies and Rare Diseases Registration Service and the methodology described can in future be applied to many rare diseases that as yet lack a way of quantifying crucial epidemiological metrics.Implications of all the available evidence The incidence of HLH is rising rapidly in people older than 5 years of age. This could be due to an increase in the biologic, immunomodulation or immunosuppressive therapy being used in people with haematological cancer and inflammatory rheumatological and bowel diseases. Further work should focus on how to minimise the risk of HLH occurring, or to improve treatment of this often fatal disease among those who need treatment for an associated comorbidity

Real‐world clinical effectiveness and safety of CT‐P10 in patients with diffuse large B‐cell lymphoma: An observational study in Europe

The rituximab biosimilar CT‐P10 is approved for the treatment of non‐Hodgkin lymphoma. Previous studies have demonstrated clinical similarity between CT‐P10 and reference rituximab. However, real‐world data relating to treatment in patients with DLBCL with rituximab biosimilars are limited. This study collected real‐world data relating to the effectiveness and safety of CT‐P10 treatment from the medical records of 389 patients with DLBCL (24 centers, five European countries). For the primary outcome (clinical effectiveness), overall survival (OS), progression‐free survival (PFS), and best response (BR) were assessed. The percentage (95% confidence interval [95% CI]) of patients alive at 12‐, 18‐, and 30 months postindex (initiation of CT‐P10) was 86% (82.4%–89.4%), 81% (76.9%–84.9%), and 76% (71.2%–80.1%), respectively. The PFS rate (percent, [95% CI]) at 12‐, 18‐, and 30 months postindex was 78% (74.2%–82.5%), 72% (67.9%–76.9%), and 67% (61.9%–71.7%), respectively. Median OS/PFS was not reached. For 82% (n = 312) of patients, the BR to CT‐P10 was a complete response. Adverse events were consistent with known effects of chemotherapy. This international, multicenter study provides real‐world data on the safety and effectiveness profile of CT‐P10 for DLBCL treatment and supports the adoption of CT‐P10 for the treatment of DLBCL