Pomalidomide Plus Low-Dose Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma and Renal Impairment: Results From a Phase II Trial

2018 ◽  
Vol 36 (20) ◽  
pp. 2035-2043 ◽  
Author(s):  
Meletios Dimopoulos ◽  
Katja Weisel ◽  
Niels W.C.J. van de Donk ◽  
Karthik Ramasamy ◽  
Barbara Gamberi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Glomerular Filtration Rate ◽  
Adverse Events ◽  
Renal Impairment ◽  
Glomerular Filtration ◽  
Phase Ii ◽  
Filtration Rate ◽  
Low Dose ◽  
Estimated Glomerular Filtration Rate ◽  
Phase Ii Trial

Purpose Renal impairment (RI) limits treatment options in patients with relapsed/refractory multiple myeloma (RRMM). Here, we prospectively studied pomalidomide plus low-dose dexamethasone (LoDEX) in patients with RRMM and moderate or severe RI, including those receiving hemodialysis. Patients and Methods MM-013, a noncomparative, European phase II trial, enrolled three patient cohorts: moderate RI (cohort A; estimated glomerular filtration rate, 30 to < 45 mL/min/1.73 m2); severe RI (cohort B; estimated glomerular filtration rate, < 30 mL/min/1.73 m2); and severe RI that requires hemodialysis (cohort C). Patients received pomalidomide 4 mg/d on days 1 to 21 and LoDEX 20 or 40 mg once per week in 28-day cycles. The primary end point was overall response rate. Results Of 81 enrolled patients (33, 34, and 14 patients in cohorts A, B, and C, respectively), 13 were still receiving treatment at data cutoff (January 28, 2017). Overall response rates were 39.4%, 32.4%, and 14.3%, with a median duration of response of 14.7 months, 4.6 months, and not estimable, respectively. Of importance, 100%, 79.4%, and 78.6% of patients, respectively, achieved disease control. With a median follow-up of 8.6 months, median overall survival was 16.4 months, 11.8 months, and 5.2 months, respectively. Complete renal responses were observed only in cohort A (18.2%), and no patients in cohort C became hemodialysis independent. Grade 3 and 4 hematologic treatment-emergent adverse events and pomalidomide discontinuations as a result of treatment-emergent adverse events occurred more frequently in cohort C. Pomalidomide pharmacokinetics were comparable among the three renal cohorts. Conclusion Pomalidomide 4 mg/d plus LoDEX is efficacious in patients with RRMM with moderate or severe RI, including those who had more advanced disease and required hemodialysis. The safety profile was acceptable among the three groups, and no new safety signals were observed.

scholarly journals Isatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in relapsed multiple myeloma patients with renal impairment: IKEMA subgroup analysis

Haematologica ◽  
2021 ◽  
Author(s):  
Marcelo Capra ◽  
Thomas Martin ◽  
Philippe Moreau ◽  
Ross Baker ◽  
Ludek Pour ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Renal Impairment ◽  
Glomerular Filtration ◽  
Subgroup Analysis ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Phase 3 ◽  
New Therapies

Renal impairment (RI) is common in patients with multiple myeloma (MM) and new therapies that can improve renal function are needed. The Phase 3 IKEMA study (NCT03275285) investigated isatuximab (Isa) with carfilzomib and dexamethasone (Kd) vs Kd in relapsed MM. This subgroup analysis examined results from patients with RI, defined as estimated glomerular filtration rate

scholarly journals Elevated admission urinary N-acetyl-β-D-glucosamidase level is associated with worse long-term clinical outcomes in patients with acute heart failure

2020 ◽  
Vol 9 (5) ◽  
pp. 429-436 ◽  
Author(s):  
Sayaka Funabashi ◽  
Kazunori Omote ◽  
Toshiyuki Nagai ◽  
Yasuyuki Honda ◽  
Hiroki Nakano ◽  
...  
Keyword(s):  
Heart Failure ◽  
Glomerular Filtration Rate ◽  
Adverse Events ◽  
Glomerular Filtration ◽  
Clinical Outcomes ◽  
Acute Heart Failure ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Prognostic Significance ◽  
Heart Failure Patients

Background: The prognostic significance of urinary N-acetyl-β-D-glucosamidase in acute heart failure has not been fully elucidated. Accordingly, this study investigated whether urinary N-acetyl-β-D-glucosamidase could be associated with subsequent adverse events in acute heart failure patients. Methods: We studied 708 consecutive acute heart failure patients who had accessible N-acetyl-β-D-glucosamidase data on admission from the National Cerebral and Cardiovascular Center Acute Decompensated Heart Failure registry. We assessed the relationship between the admission N-acetyl-β-D-glucosamidase level and the combined endpoint of all-cause death and worsening heart failure. Worsening heart failure was defined as worsening symptoms and signs of heart failure requiring intensification of intravenous therapy such as diuretics, vasodilators and inotropes or initiation of mechanical support after stabilisation with initial treatment during hospitalisation, or readmission due to heart failure after discharge. Results: During a median follow-up period of 763 (interquartile range 431–1028) days, higher urinary N-acetyl-β-D-glucosamidase was significantly related to increased events of all-cause death and worsening heart failure. In addition, patients with higher urinary N-acetyl-β-D-glucosamidase and lower estimated glomerular filtration rate on admission had the worst clinical outcomes. In multivariable Cox regression, urinary N-acetyl-β-D-glucosamidase on admission was independently associated with adverse events (hazard ratio 1.19, 95% confidence interval 1.04–1.35) even after adjustment by covariates including the baseline estimated glomerular filtration rate. Conclusions: Higher urinary N-acetyl-β-D-glucosamidase level on admission was independently associated with worse clinical outcomes. Our findings indicate the potential value of assessing urinary N-acetyl-β-D-glucosamidase on admission for further risk stratification in patients with acute heart failure.

Antimicrobial stewardship: The influence of behavioral nudging on renal-function–based appropriateness of dosing

2020 ◽  
Vol 41 (9) ◽  
pp. 1077-1079
Author(s):  
Rodrigo P. dos Santos ◽  
Caroline Deutschendorf ◽  
Hellena G. Vido ◽  
Rafaela B. Gerson ◽  
Fabiane Marson ◽  
...  
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Adverse Events ◽  
Glomerular Filtration ◽  
Antimicrobial Stewardship ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Prescription Behavior ◽  
Antimicrobial Prescription

AbstractFailure to adjust doses may contribute to adverse events. We evaluated the effectiveness of providing the estimated glomerular filtration rate on appropriateness of dosing for antimicrobials. The approach increased appropriateness of dosing from 33.9% to 41.4% (P < .001). Nudging prescription behavior can boost strategies for adequate antimicrobial prescription.

Strength of evidence for labeled dosing recommendations in renal impairment

2016 ◽  
Vol 14 (2) ◽  
pp. 219-221 ◽  
Author(s):  
Joshua J Gagne ◽  
Nazleen F Khan ◽  
Tara S Raj ◽  
Lajja R Patel ◽  
Niteesh K Choudhry
Keyword(s):  
United States ◽  
Glomerular Filtration Rate ◽  
Renal Impairment ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
The United States ◽  
Phase Iii ◽  
Pharmacokinetic Studies ◽  
Kidney Impairment

Background/Aims: Renally excreted medications often require dose adjustment in patients with kidney impairment. While drug development and approval in the United States are typically based on several Phase I and II studies and one or more larger Phase III randomized trials, the basis for labeled dosing recommendations for patients with renal impairment is less well known. In response, we aimed to quantify the level of evidence used to recommend labeled dosing adjustments for newly approved drugs in patients with renal impairment. Methods: We reviewed publicly available drug labels and approval packages for new molecular entities approved in the United States between 2012 and 2014. The sample was restricted to 29 renally excreted new molecular entities that were not granted orphan drug status. We extracted data regarding approved indications, normal dosing, dosing adjustments for patients with mild (estimated glomerular filtration rate >60 mL/min/1.73 m2), moderate (estimated glomerular filtration rate 30–<60 mL/min/1.73 m2), and severe (estimated glomerular filtration rate <30 mL/min/1.73 m2) renal impairment, characteristics of studies used to justify dosing adjustments, and numbers of subjects in each study. Results: In all, 14 of 29 (48%) new molecular entities had labels that recommended dosing adjustments for patients with mild, moderate, and/or severe renal impairment. Among these 14 new molecular entities, 4 (29%) used only pharmacokinetic studies to justify the recommendations, with no examination of clinical outcomes for patients with renal impairment. Where data were available, the median number of patients with renal impairment evaluated in studies used for dosing adjustment was 34 (range, 4–5976). Of the 15 new molecular entities with no recommended dosing adjustments for this population, 2 (13%) did not report assessing the effects of renal impairment. Conclusion: Nearly half of newly approved renally excreted drugs include dosing adjustments for kidney impairment on the label, but the recommendations are usually based on very small numbers of patients and often utilize pharmacokinetic studies alone. More research is needed to understand the benefits and risks of new drugs in patients with renal impairment.

scholarly journals Sunitinib versus sorafenib for patients with advanced renal cell carcinoma with renal impairment before the immune-oncology therapy era

2019 ◽  
Vol 49 (12) ◽  
pp. 1164-1171
Author(s):  
Tatsuya Takayama ◽  
Taro Kubo ◽  
Masahiro Yamazaki ◽  
Saki Takeshima ◽  
Maiko Komatsubara ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Glomerular Filtration Rate ◽  
Renal Impairment ◽  
Cell Carcinoma ◽  
Glomerular Filtration ◽  
Renal Cell ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Advanced Renal Cell Carcinoma ◽  
Long Term Treatment

Abstract Objectives The efficacy and safety of sunitinib versus sorafenib in patients with advanced renal cell carcinoma with renal impairment remains poorly documented. Patients and methods We assessed the efficacy and safety of sunitinib and sorafenib in patients with advanced renal cell carcinoma with an estimated glomerular filtration rate of 15–60 mL/min/1.73 m2 by reviewing the medical records of patients treated at Jichi Medical University Hospital, Japan, between May 2008 and August 2016. Results Twenty-seven patients were treated with sunitinib and 14 with sorafenib. Median progression-free survival in sunitinib- and sorafenib-treated patients was comparable, at 6.6 vs 5.8 months, respectively (HR, 1.618; 95% CI, 0.689–3.798; P = 0.2691). Median overall survival was also comparable, at 65.9 vs 58.0 months (HR, 0.985; 95% CI, 0.389–2.479; P = 0.9748). Grade 3 or higher adverse events were significantly more frequent in the sunitinib-treated than sorafenib-treated patients (P = 0.0357). Compared to pre-treatment values, estimated glomerular filtration rate at the discontinuation of treatment was not decreased in either group. In contrast, estimated glomerular filtration rate was decreased on long-term treatment, particularly in previously nephrectomized patients. Conclusions Sunitinib and sorafenib had similar efficacy in patients with advanced renal cell carcinoma and severe renal impairment. Although renal function was not markedly impaired in either group, close attention to decreased renal function may be necessary in previously nephrectomized patients on long-term treatment.

scholarly journals Determinants of Risk Factors for Renal Impairment among HIV-Infected Patients Treated with Tenofovir Disoproxil Fumarate-Based Antiretroviral Regimen in Southern Vietnam

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Cuong Q Hoang ◽  
Hai D Nguyen ◽  
Huy Q Vu ◽  
Khai T Nguyen ◽  
Linh T Hoang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Glomerular Filtration Rate ◽  
Renal Impairment ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Cross Sectional Survey ◽  
Serological Tests ◽  
Cross Sectional ◽  
Increased Risk

Background. The situation of renal impairment among HIV-infected patients treated with TDF-based antiretroviral (ARV) regimen greater than 3 years is little known when TDF use has been promptly increasing in Vietnam. Methods. We analyse demographic and clinical data from a cross-sectional survey of 400 HIV-infected patients aged ≥18 years, who were treatment-naive or switched TDF regimen within over 3 years between November 2018 and March 2019. Serological tests for serum creatinine, ALT, and AST were performed. Renal impairment was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Multivariate regression analyses were used to explore the risk factors associated with renal impairment. Results. At the baseline, 7.8% of respondents had estimated glomerular filtration rate (eGFR) of 30–59 mL/min/1.73 m2 and 0.8% had eGFR of 15–29 mL/min/1.73 m2, out of 34 (8.5%) of participants who had renal impairment. Multivariate analysis showed that participants who had preexposure to isoniazid (adjusted PR [aPR] = 0.35 Cl: 0.14–0.91) compared with nonexposure to isoniazid who had a BMI from 18.5 up to 25 kg/m2 (aPR = 0.31 Cl: 0.15–0.62) compared with BMI below 18.5 kg/m2 were less likely to suffer from renal impairment. Patients aged greater than 60 years (aPR = 26.75, 95% Cl: 3.38–211.62) compared with those aged 20–29 years were more likely to have increased risk of renal impairment. Conclusion. Our findings underscore the need for longitudinal studies to assess the influence of TDF on maintaining the low prevalence of renal impairment among HIV-infected patients in Vietnam.

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