Targeted radioimmunotherapy for embryonal tumor with multilayered rosettes.

PURPOSE: We explored the use of intraventricular 131I-Omburtamab targeting B7-H3 in patients with ETMR. METHODS: Patients were enrolled in an IRB approved, phase 1, 3 + 3 dose escalation trial. Patients with CNS disease expressing the antibody target antigen B7-H3 were eligible. We report on a cohort of three patients with ETMR who were enrolled on the study. Three symptomatic children (ages 14 months, 3 and 3.5 years) had large parietal masses confirmed to be B7-H3-reactive ETMR. Patients received 2 mCi 131I-Omburtamab as a tracer followed by one or two therapeutic 131I-Omburtamab injections. Dosimetry was based on serial CSF, blood samplings and region of interest (ROI) on nuclear scans. Brain and spine MRIs and CSF cytology were done at baseline, 5 weeks after 131I-Omburtamab, and approximately every 3 months thereafter. Acute toxicities and survival were noted. RESULTS: Patients received surgery, focal radiation, and high dose chemotherapy. Patients 1 and 2 received 131I-Omburtamab (80 and 53 mCi, respectively). Patient 3 had a local recurrence prior to 131I-Omburtamab treated with surgery, external beam radiation, chemotherapy, then 131I-Omburtamab (36 mCi). 131I-Omburtamab was well-tolerated. Mean dose delivered by 131I-Omburtamab was 68.4 cGy/mCi to CSF and 1.95 cGy/mCi to blood. Mean ROI doses were 230.4 (ventricular) and 58.2 (spinal) cGy/mCi. Patients 1 and 2 remain in remission 6.8 years and 2.3 years after diagnosis, respectively; patient 3 died of progressive disease 7 months after therapy (2 years after diagnosis). CONCLUSIONS: 131I-Omburtamab appears safe with favorable dosimetry therapeutic index. When used as consolidation following surgery and chemoradiation therapy, 131I-Omburtamab may have therapeutic benefit for patients with ETMR.

Geriatric nutritional risk index as a prognostic factor in patients with diffuse large B cell lymphoma.

The geriatric nutritional risk index (GNRI) is a simple and well-established nutritional assessment tool that is a significant prognostic factor for various cancers. However, the role of the GNRI in predicting clinical outcomes of diffuse large B cell lymphoma (DLBCL) patients has not been investigated. To address this issue, we retrospectively analyzed a total of 476 patients with newly diagnosed de novo DLBCL. We defined the best cutoff value of the GNRI as 96.8 using a receiver operating characteristic curve. Patients with a GNRI < 96.8 had significantly lower overall survival (OS) and progression-free survival (PFS) than those with a GNRI ≥ 96.8 (5-year OS, 61.2 vs. 84.4%, P < 0.001; 5-year PFS, 53.7 vs. 75.8%, P < 0.001). Multivariate analysis showed that performance status, Ann Arbor stage, serum lactate dehydrogenase, and GNRI were independent prognostic factors for OS. Among patients with high-intermediate and high-risk by National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI), the 5-year OS was significantly lower in patients with a GNRI < 96.8 than in those with a GNRI ≥ 96.8 (high-intermediate risk, 59.5 vs. 75.2%, P = 0.006; high risk, 37.4 vs. 64.9%, P = 0.033). In the present study, we demonstrated that the GNRI was an independent prognostic factor in DLBCL patients. The GNRI could identify a population of poor-risk patients among those with high-intermediate and high-risk by NCCN-IPI.

Low prognostic nutritional index predicts poor outcome in diffuse large B-cell lymphoma treated with R-CHOP.

Prognostic nutritional index (PNI), based on serum albumin concentration and the absolute peripheral lymphocyte count, has been used to predict survival in various tumors. Whether PNI can predict prognosis in patients with diffuse large B-cell lymphoma (DLBCL) remains unknown. We retrospectively analyzed 253 patients with newly diagnosed DLBCL in the present study. The PNI was calculated as: albumin (g/L) + 5 × total lymphocyte count × 10(9)/L. All patients were divided in low and high groups according to the analysis of receiver operating characteristic (ROC) curve. Low PNI was associated with more unfavorable clinical features (p < 0.05). Patients with low PNI tended to have worse event-free survival (EFS) and overall survival (OS) (EFS, p = 0.001; OS, p < 0.001). For patients treated with R-CHOP, PNI proved to be predictive for survival (EFS, p = 0.001; OS, p < 0.001), while no significant effect was found in DLBCL patients who received CHOP chemotherapy (EFS, p = 0.496; OS, p = 0.125). Multivariate analysis showed that low PNI is an independent adverse predictor of OS and EFS, especially in DLBCL patients treated with R-CHOP. In conclusion, this study suggests that PNI is an effective prognostic factor in DLBCL patients treated with R-CHOP.

Prognostic impact of sarcopenia in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

BACKGROUND: Sarcopenia is known to be related to an increased risk of chemotherapy toxicity and to a poor prognosis in patients with malignancy. We assessed the prognostic role of sarcopenia in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: In total, 187 consecutive patients with DLBCL treated with induction rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) immunochemotherapy were reviewed. Sarcopenia was defined as the lowest sex-specific quartile of the skeletal muscle index, calculated by dividing the pectoralis muscle area by the height. Clinical outcomes were compared between the sarcopenic and non-sarcopenic groups. A nomogram was constructed from the Cox regression model for overall survival (OS). RESULTS: Treatment-related mortality (21.7 vs. 5.0%, P = 0.002) and early discontinuation of treatment (32.6 vs. 14.9%, P = 0.008) were more common in the sarcopenic group than in the non-sarcopenic group. The 5 year progression-free survival (PFS) rates were 35.3% in the sarcopenic group and 65.8% in the non-sarcopenic group (P < 0.001). The 5 year OS rates were 37.3% in the sarcopenic group and 68.1% in the non-sarcopenic group (P < 0.001). Sarcopenia and the five variables of the International Prognostic Index (IPI) were independent prognostic factors in a multivariate analysis for PFS and OS and were used to construct the nomogram. The calibration plot showed good agreement between the nomogram predictions and actual observations. The c index of the nomogram (0.80) was higher than those of other prognostic indices (IPI, 0.77, P = 0.009; revised-IPI, 0.74, P < 0.001; National Comprehensive Cancer Network-IPI, 0.77, P = 0.062). CONCLUSIONS: Sarcopenia is associated with intolerance to standard R-CHOP chemotherapy as well as a poor prognosis. Moreover, sarcopenia itself can be included in prognostic models in DLBCL.

[Changes in the prognosis and treatment of Waldenström macroglobulinemia. Literature overview and own experience]. / Zmeny v prognóze a v lécbe Waldenströmovy makroglobulinemie: prehled literatury a vlastní zkusenosti.

Waldenström macroglobulinemia is defined by the presence of monoclonal immunoglobulin IgM type (M-IgM) and evidence of lymphoplasmacytic bone marrow infiltration. The disease has an indolent course, the treatment is only initiated when the disease has begun to damage its carrier. The following symptoms are regarded as proven indications for initiating therapy: B symptoms, symptomatic lymphadenopathy, splenomegaly, anemia with hemoglobin below 100 g / l or thrombocytopenia < 100 × 10(9)/l, caused by lymphoplasmacytic bone marrow infiltration. Frequent indications for initiating treatment include clinical evidence of hyperviscosity or cryoglobulinemia. M-IgM tends to have a character of autoantibody reaching up to 50 %, which may harm the organism, and therefore any proven damage to the organism by an autoimmune activity of M-IgM is also an indication for treatment. The text includes an overview of rare and very rare types of damage to the organism by M-IgM autoimmune activity. A combination of rituximab, cyclophosphamide and dexamethasone (RCD) is recommended for the initial treatment, possibly extended to R-CHOP regimen (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone). In our cohort of 43 patients the therapy involving a combination of R-CHOP achieved 3 (8.1 %) complete remissions and 31 (83.8 %) partial remissions. The remission in 75 % of the patients lasted more than 3 years. In case of recurrence after > 2 years, the same therapy can be used, in case of a relapse within a shorter period of time different treatment schedules are recommended. High-dose chemotherapy with an autologous transplant of stem cells obtained from peripheral blood is only recommended after the first recurrence for people under 65 years of age without contraindications. The text analyses the benefits of the new drugs for the treatment of Waldenström macroglobulinemia (bendamustine, thalidomide, lenalidomide, ibrutinib and high-dose chemotherapy).

Delineating outcomes of patients with diffuse large b cell lymphoma using the national comprehensive cancer network-international prognostic index and positron emission tomography-defined remission status; a population-based analysis.

The recently devised National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) appears superior to the revised IPI (R-IPI) in delineating outcome in diffuse large B-cell lymphoma. We examined the outcome of a population-based cohort of 223 consecutive patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) or R-CHOP-like immuno-chemotherapy between January 2005 and December 2011 by both the NCCN-IPI and R-IPI, and further stratified outcome by the achievement of both computerized tomography (CT) and positron emission tomography (PET)-CT complete remission (CR), with the latter reassessed using blinded central review by an independent nuclear medicine and radiology specialist. The NCCN-IPI was superior to the R-IPI in identifying patients at very high risk of systemic and/or central nervous system relapse. Notably, both the NCCN-IPI and the R-IPI remained strongly predictive of relapse irrespective of CT or PET-defined remission status following R-CHOP. Patients with high-risk NCCN-IPI scores (≥6) have a dismal outcome following R-CHOP therapy regardless of PET-defined response to R-CHOP. Moreover, such patients appear refractory to salvage chemotherapy and thus require alternative therapeutic approaches, although age and performance status may, for many patients, preclude the safe delivery of a primary intensified regimen. By contrast, patients with NCCN-IPI 1-5 who achieve PET-CR following R-CHOP have excellent outcomes and may merit reduced follow up frequency.

Brain glucose metabolism in diffuse large B-cell lymphoma patients as assessed with FDG-PET: impact on outcome and chemotherapy effects.

BACKGROUND: There is a lack of data on the effect of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy on brain glucose metabolism of diffuse large B-cell lymphoma (DLBCL) patients, as measured by 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, the prognostic value of brain glucose metabolism measurements is currently unknown. PURPOSE: To investigate the use of FDG-PET for measurement of brain glucose metabolism in R-CHOP-treated DLBCL patients, and to assess its prognostic value. MATERIAL AND METHODS: This retrospective study included DLBCL patients who underwent FDG-PET including the brain. FDG-PET metabolic volume products (MVPs) of the entire brain, cerebral cortex, basal ganglia, and cerebellum were measured, before and after R-CHOP therapy. Whole-body total lesion glycolysis (TLG) was also measured. RESULTS: Thirty-eight patients were included, of whom 18 had an appropriate end-of-treatment FDG-PET scan. There were no significant differences (P > 0.199) between pre- and post-treatment brain glucose metabolism metrics. Low basal ganglia MVP was associated with a significantly worse progression-free survival (PFS) and overall survival (OS) (P = 0.020 and P = 0.032), and low cerebellar MVP was associated with a significantly worse OS (P = 0.034). There were non-significant very weak correlations between pretreatment brain glucose metabolism metrics and TLG. In the multivariate Cox regression, only the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) remained an independent predictor of PFS (hazard ratio 3.787, P = 0.007) and OS (hazard ratio 2.903, P = 0.0345). CONCLUSION: Brain glucose metabolism was not affected by R-CHOP therapy. Low pretreatment brain glucose metabolism was associated with a worse outcome, but did not surpass the predictive value of the NCCN-IPI.

Prognostic Value of Anemia and C-Reactive Protein Levels in Diffuse Large B-Cell Lymphoma.

PURPOSE: To determine the prognostic value of pretreatment anemia, pretreatment elevated C-reactive protein (CRP) levels, and 6-month posttreatment anemia in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone (R-CHOP). PATIENTS AND METHODS: A total of 104 patients with newly diagnosed DLBCL were retrospectively included. Pretreatment hemoglobin and CRP levels and 6-month posttreatment hemoglobin levels were measured. Cox regression analyses were used to determine the associations of laboratory assessments and National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) risk groups with progression-free survival (PFS) and overall survival (OS). RESULTS: Pretreatment anemia, elevated pretreatment CRP levels, and higher risk NCCN-IPI groups were significantly associated with reduced PFS and OS (P = .001 and P = .003 for pretreatment anemia, P = .035 and P = .029 for elevated CRP, and P < .001 and P < .001 for higher risk NCCN-IPI groups). On multivariate Cox regression analysis, only the NCCN-IPI risk group remained as an independent significant predictor for PFS (P < .001) and OS (P < .001). In the subgroup of patients in complete remission 6 months after chemotherapy (n = 80), 6-month posttreatment anemia was significantly associated with reduced PFS (P = .046) but not OS (P = .062), and higher risk NCCN-IPI groups were significantly associated with both reduced PFS (P = .008) and OS (P = .017). On multivariate Cox regression analysis, only the NCCN-IPI group remained an independent significant predictor for PFS (P = .008) and OS (P = .017). CONCLUSION: Pretreatment anemia, pretreatment CRP levels, and 6-month posttreatment anemia are significantly associated with poor outcome, but were not proven to be of additional prognostic value to the current risk stratification index for DLBCL.

[Primary Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma with Large Cell Transformation of the Prostate : A Case Report].

Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the prostate is rare. MALT lymphoma with large cell transformation like a diffuse large B-cell lymphoma (DLBCL) of the prostate is extremely rare. To the best of our knowledge, only one case has been previously reported. A 65-year-old man with difficulty on urination was referred to our department, in April 2014, because of abnormal findings of magnetic resonance imaging (MRI) and positron emission tomography-computed tomography imaging. Routine laboratory tests including prostate specific antigen and soluble interletkin-2 recepter were within normal limits, and the physical examination was unremarkable. In July 2007 and August 2009, he was submitted for a transrectal prostate biopsy, and then a histological examination for chronic prostatitis. In addition to the biopsy, transurethral resection of the prostate was performed. Histological examination revealed primary MALT lymphoma with large cell transformation of the prostate. Complete clinical investigation, including bone marrow biopsy, did not show any involvement of other sites by lymphoma, he received 3 cycles of chemotherapy consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) followed by radiation therapy with a total dose of 46 Gy. The patient has been in complete remission for 6 months after the chemoradiation therapy.

Targeting of plasminogen activator inhibitor 1 improves fibrinolytic therapy for tetracycline-induced pleural injury in rabbits.

Endogenous active plasminogen activator inhibitor 1 (PAI-1) was targeted in vivo with monoclonal antibodies (mAbs) that redirect its reaction with proteinases to the substrate branch. mAbs were used as an adjunct to prourokinase (single-chain [sc] urokinase [uPA]) intrapleural fibrinolytic therapy (IPFT) of tetracycline-induced pleural injury in rabbits. Outcomes of scuPA IPFT (0.25 or 0.0625 mg/kg) with 0.5 mg/kg of mouse IgG or mAbs (MA-33H1F7 and MA-8H9D4) were assessed at 24 hours. Pleural fluid (PF) was collected at 0, 10, 20, and 40 minutes and 24 hours after IPFT and analyzed for plasminogen activating (PA), uPA, fibrinolytic activities, levels of total plasmin/plasminogen, α-macroglobulin (αM), mAbs/IgG antigens, free active uPA, and αM/uPA complexes. Anti-PAI-1 mAbs, but not mouse IgG, delivered with an eightfold reduction in the minimal effective dose of scuPA (from 0.5 to 0.0625 mg/kg), improved the outcome of IPFT (P < 0.05). mAbs and IgG were detectable in PFs at 24 hours. Compared with identical doses of scuPA alone or with IgG, treatment with scuPA and anti-PAI-1 mAbs generated higher PF uPA amidolytic and PA activities, faster formation of αM/uPA complexes, and slower uPA inactivation. However, PAI-1 targeting did not significantly affect intrapleural fibrinolytic activity or levels of total plasmin/plasminogen and αM antigens. Targeting PAI-1 did not induce bleeding, and rendered otherwise ineffective doses of scuPA able to improve outcomes in tetracycline-induced pleural injury. PAI-1-neutralizing mAbs improved IPFT by increasing the durability of intrapleural PA activity. These results suggest a novel, well-tolerated IPFT strategy that is tractable for clinical development.

Yttrium 90-ibritumomab tiuxetan plus rituximab maintenance as initial therapy for patients with high-tumor-burden follicular lymphoma: a Wisconsin Oncology Network study.

INTRODUCTION: Yttrium 90-ibritumomab tiuxetan (90Y-IT) radioimmunotherapy has proved to be effective in relapsed follicular lymphoma (FL). We conducted a clinical trial in which 90Y-IT followed by maintenance rituximab (MR) was evaluated as initial therapy for high-tumor-burden FL. METHODS: Eligible patients had histologically confirmed FL and met the GELF (Groupe d'Etude des Lymphomes Folliculaires) criteria for high tumor burden. All patients received a single dose of 90Y-IT. Patients with platelet counts of 150,000/mm³ or higher received 0.4 mCi/kg, and patients with platelet counts between 100,000/mm³ and 149,000/mm³ received 0.3 mCi/kg. At 6 months, patients without progressive disease (PD) received rituximab weekly for 4 weeks at a dose of 375 mg/m² (consolidation therapy), followed by MR consisting of the same dose every 3 months for a planned 5 years. RESULTS: From January 2005 through November 2007, a total of 16 patients were enrolled. The median age was 52 years (range, 37-75). The major toxicity from 90Y-IT was myelosuppression, with 88% and 31% of the patients experiencing grade 3 and grade 4 hematologic toxicity, respectively. The responses to 90Y-IT induction therapy were as follows: 7 patients with complete response/unconfirmed complete response (CR/Cru), 4 with partial response (PR), 3 with stable disease (SD), and 2 with progressive disease (PD). We identified 6 patients with early PD (range, 4-16 months) and 10 patients with prolonged remission (range, 37-101+ months). Compared with the patients who had prolonged remission, the patients who had early PD tended to have larger baseline nodal masses. The median progression-free survival (PFS) has not been reached after a median follow-up period of 48 months. The 3-year PFS and overall survival (OS) rates were 56% (95% CI, 37%-87%) and 93% (95% CI, 80%-100%), respectively. CONCLUSION: The overall response rate (ORR) to 90Y-IT was 69% in patients who had previously untreated, high-tumor-burden FL, which is lower than what is observed with contemporary rituximab/chemotherapy combinations. MR after 90Y-IT did convert all PRs to CRs. Alternative therapies should be considered for patients who have FL with large nodal masses (>9 cm), whereas very durable responses are possible in patients who have intermediate-size masses (>9 cm).

The use of biologicals in cutaneous allergies - present and future.

PURPOSE OF REVIEW: Up-to-date biologicals in cutaneous allergies play - unfortunately - only a minor role. However, this situation might change. Recently, omalizumab was licensed for chronic urticaria; this article reviews recent advances in the use of biologicals in cutaneous allergies. RECENT FINDINGS: Interestingly, the mechanism of omalizumab appears to be different in urticaria and allergic asthma for which the drug has been licensed previously. In urticaria dosage is not dependent on serum IgE-levels and response is seen very often after only 12 h. Other indications in cutaneous allergy in which biologicals have been investigated, at least in case reports or small studies, are TNF-α-antagonists and rituximab in chronic urticaria, omalizumab, rituximab and TNF-α-antagonists in atopic dermatitis as well as mepolizumab in this disease. However, all these studies appear to show a benefit for individual patients but not a clear breakthrough for the whole group of patients involved. This, however, might also be one of the future approaches that sub-groups of patients who have different responses to biologicals may be identified, as apparently different cytokine patterns are predominantly involved in the individual patient. SUMMARY: In conclusion, although currently only one biological is approved in chronic urticaria, there is hope that a rapid better understanding of individual disease factors will support the development of other novel drugs in this field.

[Novel treatment opportunities in Graves' orbitopathy]. / Új lehetoségek az endokrin orbitopathia kezelésében.

Graves' orbitopathy is the most common extrathyroidal manifestation of Graves' disease. Up to now, curative treatment modalities for the most severe sight-threatening cases have not been developed. Here the authors summarize the treatment protocol of Graves' orbitopathy and review novel therapeutic options. They review the literature on this topic and present their own clinical experience. The authors point out that anti-CD20 antibody could positively influence the clinical course of Graves' orbitopathy. Selenium is efficient in mild cases. Further prospective investigations are warranted.

Rituximab efficacy in the treatment of children with chronic immune thrombocytopenic purpura.

BACKGROUND: There are several medications for treatment of immune thrombocytopenic purpura (ITP), including corticosteroids, intravenous immunoglobulin, immunosuppressive drugs, and even splenectomy. In case of failure, Rituximab as one of the medications used in these patients should be considered. METHOD: This Case--series study was conducted prospectively in patients who were referred to Hematology & Oncology Clinic of Ali Asghar Hospital. Eighteen Patients were followed up for at least 3-5 years. RESULTS: Four weeks after treatment, only in 6 patients (33/3%) of 18 patients, complete response (Plt > 100,000) were obtained and most patients (67/66%) had no appropriate response. In subsequent surveys conducted at 6 and 36 months after treatment, the percentage of patients responding fell to 22/2% hit. CONCLUSION: The results of this study demonstrate proper safety of Rituximab in the treatment of chronic ITP. However, the drug had no significant effect on the expected improvement in platelet count of patients. It seems that monotherapy is ineffective in the treatment of chronic ITP and combination with other complementary therapies is recommended.

Is there still a role for abatacept in the treatment of lupus?

INTRODUCTION: The quest for safer and more effective treatments for systemic lupus erythematosus (SLE) has led to the development of many new biologic therapies. Abatacept is the first drug targeting co-stimulation between T cells and antigen presenting cells, with abundant pre-clinical evidence to support its use in SLE. AREAS COVERED: This review will present the relevant aspects of lupus pathophysiology pertaining to the mechanism of action of abatacept, a summary of murine studies and the latest human clinical trials. EXPERT OPINION: Abatacept has demonstrated efficacy in both rheumatoid arthritis and psoriatic arthritis, and earlier studies have suggested tantalising evidence of efficacy in SLE. However, the latest randomised double-blinded study showed disappointingly negative results, much like the case of rituximab in SLE. Currently, abatacept remains a possible therapeutic option as an off-label therapy, and it is a part of our therapeutic armamentarium in difficult cases. The need to find appropriate definitions of response and optimal study design continues to be paramount in the field of lupus therapies.

Survival on treatment with second-line biologic therapy: a cohort study comparing cycling and swap strategies.

OBJECTIVE: The aim of this study was to evaluate the survival on treatment with second-line biologic therapy in RA patient non-responders to TNF inhibitors (TNFis) by comparing treatments with a second anti-TNF (cycling strategy) or with agents with a different mechanism of action (MoA; swap strategy). METHODS: RA patients treated with biologics since 1999 who stopped a first-line TNFi and started a second-line biotherapy were included in this cohort study. After adjusting for propensity scores, drug retention rates were calculated using the Kaplan-Meier method. The log-rank test was used to compare survival curves and the Cox regression model was used to compare risk for discontinuation between the two groups. RESULTS: Two hundred and one patients discontinued the first TNFi, switching to a second anti-TNF [n = 119 (59.2%)] or to abatacept [n = 26 (31.7%)], rituximab [n = 40 (48.8%)] or tocilizumab [n = 15 (18.3%)]. Drug survival was significantly higher in the swap group than in the cycling group (P < 0.0001). After adjustment for propensity scores, probability of treatment retention in the swap group was significantly higher (hazard ratio = 2.258, 95% CI 1.507, 3.385), even after stratification according to the reason for the first TNFi discontinuation (P = 0.005). No significant differences emerged when comparing the retention rates of different MoAs (P = 0.51) in the swap group. CONCLUSION: In the clinical practice setting, the best option for managing TNFi non-responders seems to be swapping to a different MoA, with no differences between abatacept, rituximab and tocilizumab, irrespective of the reason for first TNFi discontinuation.

Emerging biological therapies for systemic lupus erythematosus.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with unpredictable disease course, intermingled with periods of remission and exacerbation. Current therapies for SLE are not ideal in terms of efficacy and toxicity. Although the prognosis of the disease has improved in the past decades, further improvement is hindered by the occurrence of organ damage as a result of persistent disease activity and treatment-related complications. Novel biological therapies targeting at higher treatment efficacy and fewer adverse effects are being developed. AREAS COVERED: This review summarizes recent data on novel biological therapies for SLE. The pitfalls of clinical trial design and future directions of the development of SLE therapeutics are discussed. EXPERT OPINION: The variable therapeutic response observed in SLE reflects the clinical and immunological heterogeneity of the disease. The treatment plan of SLE patients should be individualized, with the target of quenching out disease activity, minimizing disease flares, and treatment related morbidities. Despite the disappointment of recent clinical trials, avenues are being opened for novel agents that intervene at different levels of the pathophysiological cascade of SLE. With the availability of a new treatment armamentarium, it is hoped that the survival rate and quality of life of SLE patients can continue to improve.

Recent developments in the treatment of patients with systemic lupus erythematosus: focusing on biologic therapies.

INTRODUCTION: Major trials hoping to obtain optimal disease control in systemic lupus erythematosus (SLE) are ongoing. Given its complex aetiology and pathogenesis, it is not surprising that multiple therapeutic targets have emerged and that none are uniformly successful. AREAS COVERED: In this review, we highlight the recent, more significant studies focusing on the use of biologic therapies. There has been great emphasis on the role of B cells in SLE and many uncontrolled studies have encouraged the use of rituximab (an anti-CD20 monoclonal). Disappointingly, two major trials, EXPLORER and LUNAR did not confirm its utility, although doubts have been expressed on their trial design, and other trials using this drug are commencing. In contrast, belimumab, which blocks a B-cell activating factor, did meet its end points in two major randomised controlled clinical trials and has been approved for use in SLE by both the FDA and the European Medicines Agency. Encouraging, albeit preliminary, results with epratuzumab (which blocks CD22) have also been reported. EXPERT OPINION: In addition to targeting B cells, other approaches including biologics, which modulate T-cell function and block interleukin-6 and interferon-α, have been explored. Finally, we review the recent developments in the use of conventional drugs, such as cyclophosphamide and mycophenolate.

Clinical characteristics of 95 patients with ocular adnexal and uveal lymphoma: treatment outcomes in extranodal marginal zone subtype.

BACKGROUND: Lymphoma rarely presents in the ocular adnexa but is usually extranodal marginal zone (ENMZ) lymphoma when it does. Involved-field radiotherapy (IFRT) is the standard of care for unilateral disease, but the optimal management of more extensive disease is unclear. PATIENTS AND METHODS: We retrospectively evaluated the clinical characteristics and outcomes of 95 patients with ocular adnexal lymphoma (OAL) or uveal lymphoma treated or diagnosed at our institution. All patients identified were included in the risk factor analysis for progression-free survival (PFS). The initial treatment-related outcomes were assessed for ENMZ OAL only (n = 62). RESULTS: With a median follow-up of 32 months, significant risk factors for PFS after initial treatment were age (hazard ratio, 1.33; 95% confidence interval, 1.02-1.74), female gender (hazard ratio, 2.04; 95% confidence interval, 1.04-4.00), and a history of lymphoma (hazard ratio, 2.31; 95% confidence interval, 1.12-4.78). In ENMZ, IFRT was associated with improved PFS (median, 5.4 years; P < .001). Progression occurred in 7 of 39 (23%), with 6 of the 7 (86%) at systemic sites. Single-agent rituximab was typically used for bilateral ocular or systemic presentations of ENMZ OAL. Progression occurred in 7 of 11 (64%), with no progression at systemic sites. All progression events in those initially treated with rituximab occurred in the ocular adnexa. CONCLUSION: The results of the present study have confirmed IFRT as the standard for unilateral ENMZ OAL. Single-agent rituximab was an effective agent for bilateral ocular or systemic ENMZ OAL, particularly for systemic control, but ocular progression should be closely monitored. Combined modality therapy should be studied further in bilateral and systemic ENMZ OAL.

Effect of nutritional status on survival outcome of diffuse large B-cell lymphoma patients treated with rituximab-CHOP.

The impact of pretreatment nutritional status on the treatment outcome of non-Hodgkin lymphoma has never been explored. Among the 953 patients who were registered in a prospective cohort at Samsung Medical Center., we analyzed 262 patients who had been treated with Ruximab-cyclophosphamide, doxorubicin, vincristine, and prednisone for newly diagnosed diffuse large B-cell lymphoma (DLBCL) and for whom data were available regarding pretreatment nutritional status. Nutritional status at diagnosis was assessed by triceps skin fold (TSF), mid-arm muscle circumference (MAMC), body mass index (BMI), serum albumin, prealbumin, and transferrin. For patients aged 60 yr and older, poor performance and higher tumor burden were associated with malnourishment represented by albumin <3.5 g/dL, prealbumin < 17 g/dL, and transferrin <170 mg/L. Lower BMI (<20), serum albumin, prealbumin, and transferrin were identified as risk factors for febrile neutropenia in univariate analysis, but not in multivariate analysis. In the univariate analysis for OS, all nutritional parameters except MAMC showed a significant association with survival. However, BMI was the only parameter that was independently prognostic for OS in the multivariate analysis (P = 0.031; hazards ratio = 3.32). Nutritional insufficiency encountered in DLBCL patients might influence the occurrence of treatment-related toxicity and poor survival outcome of patients.