Rituximab Maintenance for the Treatment of Patients With Follicular Lymphoma: Systematic Review and Meta-analysis of Randomized Trials

Background Follicular lymphoma is characterized by slow growth and an initially high rate of response to treatment, but patients typically relapse and experience progressive disease. Rituximab in combination with chemotherapy has been shown to improve overall survival in patients with follicular lymphoma compared with chemotherapy alone, but data from randomized clinical trials evaluating rituximab maintenance treatment in these patients are limited. We aimed to evaluate the effect of maintenance treatment with rituximab on the overall survival of patients with follicular lymphoma. Methods We performed a systematic review and meta-analysis of randomized controlled trials that compared rituximab maintenance therapy with observation or treatment at relapse (no maintenance therapy). We searched The Cochrane Library, PubMed, EMBASE, LILACS, conference proceedings, databases of ongoing trials, and references of published trials. Two reviewers independently assessed the quality of the trials and extracted data. Hazard ratios for time-to-event data were estimated and pooled. Results Five trials including 1143 adult patients were included in this meta-analysis. Data for 985 patients with follicular lymphoma were available for the meta-analysis of overall survival. Patients treated with maintenance rituximab had statistically significantly better overall survival than patients in the observation arm or patients treated at relapse (hazard ratio [HR] for death = 0.60, 95% confidence interval [CI] = 0.45 to 0.79). The rate of infection-related adverse events was higher with rituximab maintenance treatment (HR = 1.99, 95% CI = 1.21 to 3.27). Patients with refractory or relapsed (ie, previously treated) follicular lymphoma had a survival benefit with maintenance rituximab therapy (HR for death = 0.58, 95% CI = 0.42 to 0.79), whereas previously untreated patients did not (HR for death = 0.68, 95% CI = 0.37 to 1.25). Conclusions These results suggest that maintenance therapy with rituximab, either as four weekly infusions every 6 months or as a single infusion every 2-3 months, should be added to standard therapy for patients with relapsed or refractory (ie, previously treated) follicular lymphoma after successful induction therapy. The higher rate of infections with rituximab therapy should be taken into consideration when making treatment decision

Rituximab Maintenance for the Treatment of Patients With Follicular Lymphoma: An Updated Systematic Review and Meta-analysis of Randomized Trials

In a previous systematic review and meta-analysis of five randomized controlled trials comparing rituximab maintenance with no maintenance (observation or rituximab at progression) for patients with follicular lymphoma, we reported that rituximab maintenance treatment improved the overall survival of patients. In this study, we did a similar search of the electronic databases updated through December 31, 2010, and included nine trials and 2586 follicular lymphoma patients. Hazard ratios (HRs) for time-to-event data were estimated and pooled using the inverse variance method. Risk ratios for dichotomous data were pooled using a fixed effect model. Patients treated with rituximab maintenance had improved overall survival (pooled HR of death = 0.76, 95% confidence interval [CI] = 0.62 to 0.92) compared with patients in the no maintenance group. Patients with refractory or relapsed (ie, previously treated) follicular lymphoma treated with rituximab maintenance had improved overall survival (pooled HR of death = 0.72, 95% CI = 0.57 to 0.91), whereas previously untreated patients had no survival benefit (pooled HR of death = 0.86, 95% CI = 0.60 to 1.25). The rate of infection-related adverse events was higher in the rituximab maintenance group (pooled risk ratio = 1.67, 95% CI = 1.40 to 2.00). These results further support the use of rituximab maintenance in the standard of care for refractory or relapsed follicular lymphom

Reported skin cancer screening of US adult workers

Early detection of skin cancer by skin examination may reduce its associated morbidity and mortality, in particular for workers routinely exposed to sun

Systematic comparison of four sources of drug information regarding adjustment of dose for renal function

Objective To compare advice on dosage adjustment for renal impairment provided by four commonly used secondary pharmacotherapeutic sources. Design Systematic comparison of the definitions of renal impairment, recommendations for dosage adjustment, and the evidence in support of these recommendations in four information sources. Data sources British National Formulary, Martindale: the Complete Drug Reference, American Hospital Formulary System Drug Information, and Drug Prescribing in Renal Failure. Review methods Two reviewers independently extracted data on recommendations for dosage adjustment for impaired renal function of 100 drugs often used in our hospital. Results The four sources differed in their recommendations for adjustments of dosage and dosing interval. They vary in their definitions of renal impairment; some are qualitative and remain unclear. All sources provide only a general description; the methods on which the advice is based and references for original data are rarely presented. Conclusions The remarkable variation in definitions and recommendations, along with scarce details of the methods used to reach this advice, makes the available sources of drug information ill suited for clinical use. The methods used to retrieve information and use data should be described and made available to the reader. Advice on drug prescription, dose and dosing interval, contraindications, and adverse effects should be evidence based

The effect of hyaluronic acid in embryo transfer media in donor oocyte cycles and autologous oocyte cycles: a systematic review and meta-analysis

STUDY QUESTION: Does the addition of hyaluronic acid (HA) to embryo transfer medium improve pregnancy outcomes in both autologous and oocyte donation IVF cycles? SUMMARY ANSWER: The best available evidence indicates that the addition of HA to embryo transfer medium is clinically beneficial in cycles with autologous oocytes. WHAT IS KNOWN ALREADY: There is a known clinical benefit of HA addition to embryo transfer media but it is not known if HA affects donor and autologous oocyte cycles differently. STUDY DESIGN, SIZE, DURATION: A systematic review with meta-analysis was performed. The Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL via Cochrane Register of Studies Online (CRSO), MEDLINE, Embase and PsycINFO electronic databases (until 8 January 2020) were searched for randomized controlled trials (RCTs) examining the effect of HA in embryo transfer medium on pregnancy outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: RCTs with separate donor and autologous oocyte data that compared embryo transfer medium with functional HA concentrations (0.5 mg/ml) to those containing no or low HA concentrations (0.125 mg/ml) were included. Two review authors independently selected trials for inclusion, extracted data and assessed the included studies using the Cochrane risk of bias assessment tool. Pooled risk ratios and 95% CIs were calculated. A summary of findings table was generated using Grading of Recommendations, Assessment, Development and Evaluation criteria. Judgements about evidence quality were justified and incorporated into the reported results for each outcome. MAIN RESULTS AND THE ROLE OF CHANCE: Fifteen studies, totalling 4686 participants, were analysed. In autologous oocyte cycles, live birth increased from 32% to 39% when embryo transfer media contained functional HA concentrations (risk ratio (RR) 1.22, 95% CI 1.11-1.34; nine studies, 3215 participants, I2 = 39%, moderate-quality evidence (number needed to treat (NNT) 14). HA-enriched media increased clinical pregnancy and multiple pregnancy rates by 5% and 8%, respectively (RR 1.11, 95% CI 1.04-1.18; 13 studies, 4014 participants, I2 = 0%, moderate-quality evidence, NNT 21) and (RR 1.49, 95% CI 1.27-1.76; 5 studies, 2400 participants, I2 = 21%, moderate-quality evidence, number needed to harm 13). Conversely, in donor oocyte cycles, HA addition showed little effect on live birth and clinical pregnancy (RR 1.12 95% CI 0.86-1.44; two studies, 317 participants, I2 = 50%, low-quality evidence) and (RR 1.06, 95% CI 0.97-1.28; three studies, 351 participants, I2 = 23%, low-quality evidence). There was insufficient available information on multiple pregnancy in donor oocyte cycles and on total adverse effects in both groups to draw conclusions. LIMITATIONS, REASONS FOR CAUTION: There were limited studies with separate data on donor oocyte cycles and limited information on oocyte quality. Additionally, one-third of the included studies did not include the main outcome, live birth rate. WIDER IMPLICATIONS OF THE FINDINGS: There is a moderate level of evidence to suggest that functional HA concentration in embryo transfer medium increases clinical pregnancy, live birth and multiple pregnancy rates in IVF cycles using autologous oocytes. This effect was not seen in donor oocyte cycles, indicating either intrinsic differences between donor and autologous oocytes or lack of statistical power. The combination of HA addition to transfer media in cycles using autologous oocytes and a single embryo transfer policy might yield the best combination, with higher clinical pregnancy and live birth rates without increasing the chance of multiple pregnancies. STUDY FUNDING/COMPETING INTEREST(S): No financial assistance was received. The authors have no competing interests. REGISTRATION NUMBER: N/A