Estudio primario

No clasificado

High Ki-67 expression in diffuse large B-cell lymphoma patients with non-germinal center subtype indicates limited survival benefit from R-CHOP therapy.

Año 2012
Autores Li ZM , Huang JJ , Xia Y , Zhu YJ , Zhao W , Wei WX - Más
Revista European journal of haematology
Enlaces Pubmed , DOI

Este artículo está incluido en 1 Revisión sistemática Revisiones sistemáticas (1 referencia)

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OBJECTIVES:

Rituximab has significantly improved the survival of patients with DLBCL, especially those with non-germinal center B-cell-like (non-GCB) subtype. The impact of Ki-67 expression, an index of proliferation, on the clinical outcomes of patients with DLBCL has largely been unexplored. This study aimed to investigate whether Ki-67 expression is an indicator of outcome in DLBCL patients (especially non-GCB DLBCL patients) treated with standard chemotherapy combined with rituximab.

METHODS:

Expression of Ki-67 protein was examined immunohistochemically in 118 tumor specimens from patients newly diagnosed with DLBCL and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

RESULTS:

Overall survival (OS) and progression-free survival (PFS) were lower in patients with high Ki-67 expression than in those with low Ki-67 expression (3-year OS.: 65.2% vs. 81.7%, P = 0.030; 3-year

PFS:

56.4% vs. 73.3%, P = 0.020), similar in patients with GCB subtype and those with the non-GCB subtype (OS: P = 0.330;

PFS:

P = 0.287). According to Ki-67 expression status by immunophenotype subgroups, patients with high Ki-67 expression in non-GCB subgroup had the most unfavorable PFS and OS, comparing with the other three subgroups (P = 0.004 and P = 0.002, respectively). In multivariate analysis, non-GCB with high Ki-67 expression was an independent prognostic predictor of inferior survival in DLBCL patients treated with R-CHOP.

CONCLUSION:

For DLBCL patients with non-GCB DLBCL and high Ki-67 expression, the survival benefit from R-CHOP therapy is limited.

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Revisión sistemática

No clasificado

Mixed treatment comparison of the treatment discontinuations of biologic disease-modifying antirheumatic drugs in adults with rheumatoid arthritis.

Año 2012
Revista The Annals of pharmacotherapy
Enlaces Pubmed , DOI

Este artículo incluye 50 Estudios primarios 49 Estudios primarios (50 referencias)

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BACKGROUND:

Introduction of biologic disease-modifying antirheumatic drugs (DMARDs) has considerably changed treatment options for rheumatoid arthritis (RA) over the past decade. Very little information is available on comparative discontinuation rates of the biologics.

OBJECTIVE:

To compare treatment discontinuations for 9 biologic DMARDs in adults with RA.

METHODS:

We searched electronic databases through May 2012 to retrieve randomized controlled trials (RCTs) of patients with RA that compared biologic DMARDs with placebo or another biologic DMARD. The primary outcome was treatment discontinuation during the blinded phase of the trials, measured as overall withdrawals, withdrawals resulting from lack of efficacy, and withdrawals resulting from adverse events. Random-effects meta-analysis estimated the effect size for individual agents, and adjusted indirect comparisons were made between biologics using mixed treatment comparisons (MTC) meta-analysis.

RESULTS:

Forty-four trials were included in the analysis. In comparison with placebo, biologics were less likely to be withdrawn because of lack of efficacy (OR 0.22, 95% CI 0.17 to 0.27) and more likely to be withdrawn because of an adverse event (OR 1.41, 95% CI 1.16 to 1.70). Based on the MTC, certolizumab had the most favorable overall withdrawal profile, followed by etanercept and rituximab. Certolizumab had lower relative withdrawal rates resulting from lack of efficacy than adalimumab, anakinra, and infliximab. Anakinra had higher relative withdrawal rates resulting from lack of efficacy than most other biologics. Certolizumab and infliximab had more, while etanercept had fewer, withdrawals because of adverse events than most other drugs.

CONCLUSIONS:

Based on MTC using data from RCTs, differences in discontinuation rates were observed, generally favoring certolizumab, etanercept, and rituximab over other biologic DMARDs. These potential differences need to be further explored in head-to-head trials or well-conducted observational studies.

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Revisión sistemática

No clasificado

Use of biologics in rheumatoid arthritis: current and emerging paradigms of care.

Año 2011
Autores Curtis JR , Singh JA
Revista Clinical therapeutics
Enlaces Pubmed , PMC , DOI

Sin referencias

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BACKGROUND:

Improved understanding of rheumatoid arthritis (RA) pathogenesis has led to the development of new biologic treatments that target specific elements of RA inflammatory response.

OBJECTIVE:

Our aim was to provide a comprehensive review of biologic therapies currently used for the treatment of RA.

METHODS:

A search of MEDLINE (up to October 2010) was conducted. Preference for article inclusion was given to English language meta-analyses and large, Phase III, randomized controlled trials (RCTs) of biologic treatments in patients with RA.

RESULTS:

In large RCTs, significantly more patients treated with tumor necrosis factor-α (TNF-α) antagonists (as monotherapy, or as an adjunct to methotrexate) versus controls (35%-67% vs 9%-33% of patients; P ≤ 0.01) achieved an American College of Rheumatology 20 response as a primary study end point. However, safety concerns-especially the potential for serious infections and malignancy-remain for TNF-α blockade. For example, 1 meta-analysis (>5000 patients) reported a 2-fold increase (95% CI, 1.3-3.1) in the risk of serious infections and a 3.3-fold increase (95% CI, 1.2-9.1) in the risk of malignancy. Abatacept and rituximab (given in combination with methotrexate) may be useful clinical alternatives for RA patients with an inadequate response to TNF-α antagonists. These agents do not appear to increase the risk of serious infections (OR, 1.35-1.45; 95% CI, 0.56-3.73), although rituximab may rarely cause progressive multifocal leukoencephalopathy (0.4 cases per 100,000 hospitalizations).

CONCLUSIONS:

Over the last decade, targeted biologic agents have transformed RA treatment. Although relatively expensive in the short term, the direct costs of these biologics may be offset by slowed disease progression and significant improvements in RA symptoms, physical function, and quality of life.

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Revisión sistemática

No clasificado

Biosimilars for the Treatment of Cancer: A Systematic Review of Published Evidence.

Año 2017
Autores Jacobs I , Ewesuedo R , Lula S , Zacharchuk C
Revista BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy
Enlaces Pubmed , PMC , DOI

Este artículo incluye 31 Estudios primarios 30 Estudios primarios (31 referencias)

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BACKGROUND:

Biologic treatments for cancer continue to place a significant economic burden on healthcare stakeholders. Biosimilar therapies may help reduce this burden through cost savings, thereby increasing patient access.

OBJECTIVES:

The purpose of this study was to collate all published data to assess the weight of available evidence (quantity and quality) for proposed monoclonal antibody biosimilars and intended copies, for the treatment of cancer.

METHODS:

MEDLINE(®), Embase(®), and ISI Web of Science(®) databases were searched to September 2015. Conference proceedings (17) were searched (2012 to July 2015). Searches of the United States National Library of Medicine ClinicalTrials.gov registry were also conducted. Risk of bias assessments were undertaken to assess data strength and validity.

RESULTS:

Proposed biosimilars were identified in 23 studies (36 publications) in oncology and ten studies in 14 publications in oncology and chronic inflammatory diseases for bevacizumab, rituximab, and trastuzumab originators. Based on our review of the included published studies, and as inferred from the conclusions of study authors, the identified proposed biosimilars exhibit close similarity to their originators. Published data were also retrieved on intended copies of rituximab. It remains unclear what role these agents may have, as publications on rigorous clinical studies are lacking for these molecules.

CONCLUSION:

While biosimilar products have the potential to improve patient access to important biologic therapies, robust evidence of outcomes for monoclonal antibody biosimilars in treating cancer patients, including data from comparative efficacy and safety trials, is not yet available in the published literature. Significant data gaps exist, particularly for intended copies, which reinforces the need to maintain a clear differentiation between these molecules and true biosimilars. As more biosimilars become available for use, it will be important for stakeholders to understand fully the robustness of overall evidence used to demonstrate biosimilarity and gain regulatory approval.

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Revisión sistemática

No clasificado

Primary cutaneous B-cell lymphomas: recent advances in diagnosis and management.

Año 2012
Autores Sokol L , Naghashpour M , Glass LF
Revista Cancer control : journal of the Moffitt Cancer Center
Enlaces Pubmed , DOI

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BACKGROUND:

Primary cutaneous B-cell lymphoma (PCBCL) is a heterogeneous group of rare clonal B-cell lymphoproliferative disorders with distinct clinicopathologic features from more common nodal B-cell lymphomas.

METHODS:

We performed a systematic review of the relevant literature in the MEDLINE database and analyzed laboratory and clinical data. This review discusses the three most common types of

PCBCL:

primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle-center lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT).

RESULTS:

Skin biopsies with histology, immunohistochemistry, and molecular clonality studies are essential for a correct diagnosis of cutaneous B-cell lymphoma. Comprehensive lymphoma staging with laboratory and imaging studies and bone marrow aspiration and biopsy are important for determining the prognosis and differentiation of PCBCL from secondary skin involvement with systemic B-cell lymphomas. PCMZL and PCFCL are low-grade PCBCLs, with an estimated 5-year disease-specific survival rate of greater than 95%. Surgical excision or focal radiation therapy is sufficient to control stages T1 and T2 disease. Rituximab monotherapy is frequently used for patients with stage T3 disease. PCDLBCL, LT is an intermediate-grade B-cell lymphoma, with a 5-year disease-specific survival rate of approximately 50%. An anthracycline-based chemotherapy regimen with rituximab is usually required as initial therapy to improve outcomes.

CONCLUSIONS:

In less than a decade, significant progress has been made in our understanding of PCBCL. Novel classification, staging, and prognostic systems have resulted in more accurate diagnosis and prognosis. Although no randomized prospective studies have been conducted in PCBCL, therapies derived from systemic B-cell lymphomas have shown promising results.

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Estudio primario

No clasificado

Therapeutic ladder for pemphigus vulgaris: emphasis on achieving complete remission.

Año 2011
Revista Journal of the American Academy of Dermatology
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BACKGROUND:

Pemphigus vulgaris (PV) is a blistering autoimmune bullous disease that is usually fatal without proper treatment. There are no clear treatment guidelines for PV at this time.

PURPOSE:

We suggest a standard treatment regimen for patients with PV based on the success of our treatment.

METHODS:

A retrospective chart review of 18 patients with PV was conducted to assess response to a similar approach using mycophenolate mofetil (MMF) and prednisone. Diagnosis was confirmed through routine histology, direct immunofluorescence, and indirect immunofluorescence, and patients were followed up for a total average of 35.2 months.

RESULTS:

We achieved complete disease control in 89% of patients using our treatment algorithm. Fourteen of 18 patients achieved complete disease control on therapy with prednisone and MMF. Three of the 4 patients who did not achieve control on MMF and prednisone went on to receive rituximab therapy, and two of those patients achieved disease control on rituximab. The average length of time from initiating therapy to 75% clearance of lesions was 4.5 months. Three of 18 patients were able to discontinue therapy after an average of 3 years and have remained in complete remission for more than 1 year.

LIMITATIONS:

This was a retrospective chart review with a small patient sample size.

CONCLUSIONS:

The combination therapy of MMF and prednisone is an effective treatment regimen to achieve rapid and complete control of PV. For those patients who fail treatment with MMF and prednisone, rituximab is an efficacious alternative therapy.

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Estudio primario

No clasificado

Autologous hematopoietic stem cell transplantation for relapsed follicular lymphoma: safety profile and clinical outcome in a single-center experience.

Año 2014
Revista Medical oncology (Northwood, London, England)
Enlaces Pubmed , DOI

Este artículo no está incluido en ninguna revisión sistemática

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Autologous hematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsed and recurrent follicular lymphoma (R/R FL); however, its value in the rituximab era remains to be elucidated. To evaluate the safety and clinical outcome of AHSCT for relapsed FL, we present a retrospective series of AHSCT for 30 FL patients (17 male and 13 female) at median age of 49 years. Patients were transplanted in second or subsequent complete or partial response after at least one therapeutic line including chemotherapy and rituximab. Overall, seven patients achieved second or higher complete response (CR) at AHSCT, whereas 23 were transplanted in partial response. Median overall survival (OS) was not reached, whereas progression-free survival (PFS) was 4.8 years. The estimated 10-year OS and PFS were found to be 60 and 33%, respectively. There was no significant difference in OS and PFS in terms of FLIPI score and disease status at transplant. Median follow-ups from diagnosis and from AHSCT were 4.9 years (range 1.5-18.4 years) and 1.7 years (range 0.03-16.5 years), respectively. Fifteen patients relapsed, and 11 out of them (73%) died of disease recurrence and chemoresistance. At the last contact, 19 patients are alive: 12 are in CR, whereas seven patients receive salvage regimens due to active lymphoma. AHSCT for relapsed FL patients who were pretreated with rituximab remains a safe procedure with low transplant-related mortality and long-term progression-free survival in about one-third of transplanted patients.

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Estudio primario

No clasificado

Prognostic impact of immunohistochemically defined germinal center phenotype in diffuse large B-cell lymphoma patients treated with immunochemotherapy.

Año 2007
Revista Blood
Enlaces Pubmed , DOI

Este artículo está incluido en 1 Revisión sistemática Revisiones sistemáticas (1 referencia) 1 Síntesis amplia Síntesis amplias (1 referencia)

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Germinal center (GC) and non-GC phenotypes are predictors of outcome in diffuse large B-cell lymphoma (DLBCL) and can be used to stratify chemotherapy-treated patients into low- and high-risk groups. To determine how combination of rituximab with chemotherapy influences GC-associated clinical outcome, GC and non-GC phenotypes were identified immunohistochemically from samples of 90 de novo DLBCL patients treated with rituximab in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimen (immunochemotherapy). One hundred and four patients previously treated with chemotherapy served as a control group. Consistent with previous studies, chemotherapy-treated patients with immunohistochemically defined GC phenotype displayed a significantly better overall (OS) and failure-free survival (FFS) than the non-GC group (OS, 70% vs 47%, P = .012; FFS, 59% vs 30%, P = .001). In contrast, immunohistochemically defined GC phenotype did not predict outcome in immunochemotherapy-treated patients (OS, 77% vs 76%, P = ns; FFS, 68% vs 63%, P = ns). In comparison, International Prognostic Index (IPI) could separate the high-risk patients from low- and intermediate-risk groups (OS, 84% vs 63%, P = .030; FFS, 79% vs 52%, P = .028). We conclude that rituximab in combination with chemotherapy seems to eliminate the prognostic value of immunohistochemically defined GC- and non-GC phenotypes in DLBCL.

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Estudio primario

No clasificado

Multicenter longitudinal study of B-lymphocyte depletion in refractory systemic lupus erythematosus: the LESIMAB study.

Año 2012
Revista Lupus
Enlaces Pubmed , DOI

Este artículo está incluido en 3 Revisiones sistemáticas Revisiones sistemáticas (3 referencias)

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OBJECTIVE:

This study aimed to investigate the effectiveness and safety of single and repeated courses of rituximab in patients with refractory lupus.

METHODS:

LESIMAB is a multicenter, retrospective, longitudinal study of lupus patients who have not responded to standard therapy and have been treated with rituximab. Response rates at six months and at follow-up were defined as efficacy outcomes. Complete response was defined as a SELENA-SLEDAI score ≤ two and a SELENA-SLEDAI Flare Index of zero. Partial response was defined as a reduction in the SELENA-SLEDAI score of ≥four points with no new or worsening of symptoms. Adverse events were collected.

RESULTS:

Seventy-three (62.9%) of 116 patients achieved a response at six months (complete in 22 and partial in 51). Ninety-seven (77.6%) of 128 patients achieved a response after a mean follow-up of 20.0 ± 15.2 months (complete in 50 and partial in 47). High baseline SLEDAI score, previous treatment with ≥100 mg/day prednisone, and no history of severe hematologic flare were associated with response after the first treatment course. The median time to response was 6.5 months (95% CI, 5.0-8.0). Thirty-seven patients (38.1%) relapsed after the first infusion. The flare was severe in seven cases and mild to moderate in 29 cases. Serious infection rate was 12.6/100 patient-years. A schedule of four weekly doses was associated with more serious infections. Six patients died: two of infection and four of lupus complications.

CONCLUSION:

Rituximab can be an effective treatment option for patients who have refractory lupus with severe or life-threatening disease with an acceptable tolerance profile.

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Estudio primario

No clasificado

Double hit lymphoma: the MD Anderson Cancer Center clinical experience.

Año 2014
Revista British journal of haematology
Enlaces Pubmed , DOI

Este artículo no está incluido en ninguna revisión sistemática

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We report our experience with 129 cases of double hit lymphoma (DHL), defined as B-cell lymphoma with translocations and/or extra signals involving MYC plus BCL2 and/or BCL6. All cases were reviewed for histopathological classification. Median age was 62 years (range, 18-85), 84% of patients had advanced-stage disease, and 87% had an International Prognostic Index score ≥2. Fourteen patients (11%) had a history of low-grade follicular lymphoma. MYC translocation was present in 81%, and extra signals of MYC in 25% of patients. IGH-BCL2 translocation was present in 84% and extra signals of BCL2 in 12% of patients. Two-year event-free survival (EFS) rates in all patients and patients who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), and R-HyperCVAD/MA (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, alternating with cytarabine plus methotrexate) were 33%, 25%, 67% and 32%, respectively. In patients achieving complete response with initial therapy (n = 71), 2-year EFS rates in patients who did (n = 23) or did not (n = 48) receive frontline stem cell transplantation were 68% and 53%, respectively (P = 0·155). The cumulative incidence of central nervous system involvement was 13% at 3 years. Multivariate analysis identified performance status ≥2 and bone marrow involvement as independent adverse prognostic factors for EFS and OS. Further research is needed to identify predictive and/or targetable biological markers and novel therapeutic approaches for DHL patients.

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