Risk of infection in patients with lymphoma receiving rituximab: systematic review and meta-analysis

Lanini, Simone; Molloy, Aoife; Fine, Paul E. M.; Prentice, A. G.; Ippolito, Giuseppe; Kibbler, Christopher C.

doi:10.1186/1741-7015-9-36

Cited by 85 publications

(65 citation statements)

References 40 publications

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“…However, data in patients with autoimmune diseases or lymphoproliferative disorders exposed to extremely higher doses than in this study, or receiving long-life rituximab therapy for chronic lymphomas, consistently show that rituximab is remarkably safe, particularly compared with other immunosuppressants, over $10 years. [25][26][27] An important difference between previous studies and this study is that selection of patients with long-lasting nephrotic syndrome despite ACE inhibitor therapy allowed us to reasonably exclude any appreciable confounding effect of spontaneous remissions. Moreover, none of our patients had evidence of myelotoxicity, lymphoproliferative disorders, or life-threatening opportunistic infections, and the three cases of cancer observed in 100 patients over a median follow-up of 29 months reflects the age-adjusted incidence of neoplastic disease in the general population.…”

Section: Discussionmentioning

confidence: 50%

Rituximab in Idiopathic Membranous Nephropathy

Ruggenenti

Cravedi

Chianca

et al. 2012

Journal of the American Society of Nephrology

276

213

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Selective depletion of B cells with the mAb rituximab may benefit the autoimmune glomerular disease idiopathic membranous nephropathy (IMN). Here, we describe our experience treating 100 consecutive IMN patients with persistent nephrotic syndrome with rituximab. We defined complete remission as persistent proteinuria ,0.3 g/24 h and partial remission as persistent proteinuria ,3 g/24 h, each also having .50% reduction in proteinuria from baseline. During a median follow-up of 29 months after rituximab administration, 65 patients achieved complete or partial remission. The median time to remission was 7.1 months. All 24 patients who had at least 4 years of follow-up achieved complete or partial remission. Rates of remission were similar between patients with or without previous immunosuppressive treatment. Four patients died and four progressed to ESRD. Measured GFR increased by a mean 13.2 (SD 19.6) ml/min per 1.73 m 2 among those who achieved complete remission. Serum albumin significantly increased and albumin fractional clearance decreased among those achieving complete or partial remission. Proteinuria at baseline and the follow-up duration each independently predicted the decline of proteinuria. Furthermore, the magnitude of proteinuria reduction significantly correlated with slower GFR decline (P=0.0001). No treatment-related serious adverse events occurred. In summary, rituximab achieved disease remission and stabilized or improved renal function in a large cohort of high-risk patients with IMN.

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Section: Discussionmentioning

confidence: 50%

Rituximab in Idiopathic Membranous Nephropathy

Ruggenenti

Cravedi

Chianca

et al. 2012

Journal of the American Society of Nephrology

276

213

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“…Rituximab possibly increased the infection risk. 10 A high delivered-dose intensity, coupled with avoidance of growth factors, possibly contributed, although others have reported low infection incidences with similar strategies. 11 Rituximab has been increasingly evaluated in cHL, 2,12-16 although its role and mechanism in cHL are not fully understood.…”

Section: Resultsmentioning

confidence: 99%

Phase 2 study of rituximab-ABVD in classical Hodgkin lymphoma

Kasamon

Jacene

Gocke

et al. 2012

Blood

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In classical Hodgkin lymphoma, circulating clonotypic malignant cells express CD20, which potentially explains the observed activity of rituximab. This multicenter phase 2 study investigated the combination of rituximab-ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for stage II-IV untreated classical Hodgkin lymphoma. A goal was to assess the behavior of circulating clonotypic B cells clinically. Of 49 evaluable patients, 69% had stage IIB-IV disease; 8% had CD20 ؉ Hodgkin and ReedSternberg cells. Rituximab-ABVD was generally well tolerated. Delivered relative dose intensity was 94% for AVD and 79% for bleomycin. After 6 cycles, 81% of patients were in complete remission. Only 8% received radiation therapy. The actuarial 3-year event-free and overall survival rates were 83% and 98%, respectively. EBV copy num- IntroductionIn classical Hodgkin lymphoma (cHL), responses to rituximab can occur in patients whose Hodgkin and Reed-Sternberg (HRS) cells lack CD20 expression. 1,2 Interestingly, morphologically distinct subpopulations were described within a human cHL cell line more than 20 years ago. 3 Clonogenic potential appeared to be largely limited to rare CD19 ϩ mononuclear cells that were phenotypically distinct from HRS cells. 3 The Johns Hopkins group recently reported that within cHL cell lines, this small population has a memory B-cell phenotype, is enriched for the stem cell marker aldehyde dehydrogenase, and appears to generate and sustain the growth of HRS cells. 4 Furthermore, such rare clonotypic B cells circulated in most patients with newly diagnosed cHL, including those with limited-stage disease, and had the same immunoglobulin gene rearrangements as lymph node-derived HRS cells. 4 These findings potentially explain the observed activity of rituximab in cHL and raise the possibility that anti-B-cell therapies represent new approaches for this disease.A phase 2 trial of rituximab combined with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for cHL was conducted to explore its biologic effects in correlative laboratory studies and secondarily to evaluate clinical outcomes. MethodsThis single-arm, institutional review board-approved study was conducted through an inter-SPORE (Lymphoma Specialized Program of Research Excellence) collaboration. All participants gave written consent. Eligibility criteria included untreated stage II-IV cHL; age Ն 18 years; negative for HIV and hepatitis B surface antigen; creatinine Յ 2 mg/dL; and bilirubin Յ 5 mg/dL. Specified treatment was 6-8 cycles of standard ABVD with rituximab 375 mg/m 2 1 week before ABVD initiation; on days 1, 8, 15, and 22 of cycle 1 ABVD; and on day 1 of cycles 2, 4, and 6. Once-weekly rituximab was given to maximize B-cell depletion early in the course. 1 Sample size was based on correlative laboratory end points. Some pretreatment clonotypic B-cell data were included in a previous report. 4 Blood specimens were collected at baseline, during chemotherapy, 2-4 weeks afterward, and then every 2-6 months. Table 1 summarizes the ...

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“…However, data in patients with autoimmune diseases or lymphoproliferative disorders exposed to extremely higher doses than the ones used to treat MN, or receiving long-life rituximab therapy for chronic lymphomas, consistently show that rituximab is remarkably safe, particularly compared with other immunosuppressants, over ≥10 years [42,43,44]. …”

Section: Rituximabmentioning

confidence: 99%

Rituximab in Primary Membranous Nephropathy: First-Line Therapy, Why Not?

2014

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The ideal treatment of patients with primary membranous nephropathy (MN) and persistent nephrotic syndrome (NS) is still a matter of debate. This is a major issue since these patients may progress to end-stage kidney disease (ESKD) in 5-10 years. Steroids, alkylating agents, and calcineurin inhibitors have been suggested to achieve NS remission and prevent ESKD in this population. Treatment benefits, however, are uncertain and are often offset by serious adverse events (SAEs). Evidence that B cells play a crucial role in the pathogenesis of the disease, both as precursors of autoantibody-producing cells and as antigen-presenting cells, provided the background for explorative studies testing the role of B cell-depletion therapy with the monoclonal antibody rituximab. This approach aimed at selectively inhibiting disease mechanisms without the devastating consequences of unspecific immunosuppression. Finding that rituximab safely ameliorated NS in 8 patients with primary MN fueled a series of observational studies that uniformly confirmed the safety/efficacy profile of rituximab in this context. Although head-to-head comparisons in randomized clinical trials are missing, comparative analyses between series of homogeneous patient cohorts clearly show at least similar efficacy of rituximab as compared to steroid plus alkylating agents. Moreover, data confirm the dramatically superior safety profile of rituximab that actually appears to be associated with a rate of SAEs even lower than that observed with conservative therapy. Rituximab is also effective in patients resistant to other treatments and its cost-effectiveness is further increased when treatment is titrated to circulating B cells. Recently identified pathogenic antibodies against the M type phospholipase A₂ receptor will likely provide a novel tool to monitor disease activity and drive rituximab therapy, at least in a subset of patients. Newly developed anti-CD20 antibodies could represent a valuable option for those who fail rituximab therapy. Steroids, alkylating agents, and calcineurin inhibitors should likely be abandoned.

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Risk of infection in patients with lymphoma receiving rituximab: systematic review and meta-analysis

Cited by 85 publications

References 40 publications

Rituximab in Idiopathic Membranous Nephropathy

Rituximab in Idiopathic Membranous Nephropathy

Phase 2 study of rituximab-ABVD in classical Hodgkin lymphoma

Rituximab in Primary Membranous Nephropathy: First-Line Therapy, Why Not?

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