Citations

IgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody–producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy–proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin–converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR<90 ml/min per 1.73 m 2 , to receive standard therapy or rituximab with standard therapy. Primary outcome measures included change in proteinuria and change in eGFR. Median baseline serum creatinine level (range) was 1.4 (0.8–2.4) mg/dl, and proteinuria was 2.1 (0.6–5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in each group had ≥50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose–deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy.

A preclinical study demonstrated anti‐proliferative and apoptotic effect of propranolol on multiple myeloma (MM) cell. Clinical studies suggested that beta‐blocker (BB) might impact the prognosis of breast, prostate, colorectal, ovarian, lung, and skin cancer. This retrospective study evaluated the effect of BB in MM disease‐specific survival (DSS) and overall survival (OS). Among 1,971 newly diagnosed MM patients seen at Mayo Clinic between 1995 and 2010, usage of BB and other cardiac (or antihypertensive) medications were abstracted. Cumulative incidence function and Kaplan–Meier method were used to estimate 5‐year cumulative incidence rate (CIR) of MM death and OS rate, respectively. Nine hundred and thirty (47.2%) patients had no intake of cardiac medications; 260 (13.2%) used BB alone; 343 (17.4%) used both BB/non‐BB cardiac medications; and 438 (22.2%) had non‐BB cardiac drugs. Superior MM DSS was observed in BB only users, compared to patients without any cardiac drugs ( , 0.53, 95% confidence interval [CI], 0.42–0.67, Padj.<0.0001) and non‐BB cardiac drugs users ( , 0.49, 95% CI, 0.38–0.63, Padj.<0.0001). Patients on both BB and other cardiac drugs showed superior DSS than non‐cardiac drugs users ( , 0.54, 95% CI, 0.44–0.67, Padj.<0.0001) and non‐BB cardiac drug users. ( , 0.50, 95% CI, 0.40–0.62, Padj.<0.0001). MM DSS did not differ between BB users with and without other cardiac drugs (Padj.=0.90). Multivariable analysis showed the same pattern for OS. In patients with MM, BB intake is associated with a reduced risk of disease‐specific death and overall mortality in comparison to non‐BB or no use of cardiac drugs. Am. J. Hematol. 92:50–55, 2017. © 2016 Wiley Periodicals, Inc.

Key PointsThe monotypic and polytypic PC compartments assessed by MFC are prognostic in AL amyloidosis. MFC may play a role in the definition of hematologic response to treatment.

Introduction: The therapeutic trough range for mexiletine (0.8–2 mcg/mL) was largely established in the setting of arrhythmia prophylaxis following myocardial infarction. Objective: Describe the usage patterns of serum mexiletine concentrations and the impact of these concentrations on mexiletine dosing in modern practice for ventricular arrhythmia treatment. Methods: A single-center, retrospective analysis was conducted using the electronic medical record to identify serum mexiletine concentrations drawn between December 2004 and December 2014. The primary endpoint was the incidence of mexiletine concentrations drawn as troughs. Secondary outcomes included the incidence of mexiletine concentrations that prompted a dose change, association between adverse events and elevated concentrations, and association between baseline characteristics and mexiletine concentrations. Results: A total of 237 individual concentrations were included for analysis with 109 (46.0%) drawn appropriately as trough concentrations. Only 31 (13.1%) of the 237 concentrations drawn prompted a dose change. Mexiletine was primarily used for the treatment of ventricular arrhythmias (96.2%), and 108 (45.6%) concentrations were drawn in an effort to assess efficacy. The median concentration was statistically different between patients with and without an adverse event (0.8 vs 0.7 mcg/mL, respectively; p = 0.017), but may not represent a clinical significance. Patients with hepatic dysfunction had higher median concentrations compared to those without hepatic dysfunction (1.30 vs 1.07 mcg/mL; p = 0.01). Conclusion: Mexiletine concentrations are often drawn at inappropriate times and seldom influence a dose change. This study suggests that routine monitoring of mexiletine concentrations may not be necessary; however, therapeutic drug monitoring may be considered in patients with hepatic dysfunction or to confirm mexiletine absorption in patients where this represents a concern.

Purpose To determine the effects of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) on health-related quality of life (HR-QoL) in the Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone for the Treatment of Patients With Relapsed Multiple Myeloma (ASPIRE) trial. Methods Patients with relapsed multiple myeloma were randomly assigned to receive KRd or Rd. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and myeloma-specific module were administered at baseline; day 1 of cycles 3, 6, 12, and 18; and after treatment. The Global Health Status/Quality of Life (GHS/QoL) scale and seven subscales (fatigue, nausea and vomiting, pain, physical functioning, role functioning, disease symptoms, and adverse effects of treatment) were compared between groups using a mixed model for repeated measures. The percentages of responders with ≥ 5- or 15-point GHS/QoL improvement at each cycle were compared between groups. Results Baseline questionnaire compliance was excellent (94.1% of randomly assigned patients). KRd patients had higher GHS/QoL scores versus Rd patients over 18 treatment cycles (two-sided P < .001). The minimal important difference was met at cycle 12 (5.6 points) and approached at cycle 18 (4.8 points). There was no difference between groups for the other prespecified subscales from ASPIRE. A higher proportion of KRd patients met the GHS/QoL responder definition (≥ 5-point improvement) with statistical differences at cycle 12 (KRd v Rd patients, 25.5% v 17.4%, respectively) and 18 (KRd v Rd patients, 24.2% v 12.9%, respectively). Conclusion KRd improves GHS/QoL without negatively affecting patient-reported symptoms when compared with Rd. These data further support the benefit of KRd in patients with relapsed multiple myeloma.