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

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 Effect of severe renal impairment on the pharmacokinetics of brigatinib

2021 ◽  
Author(s):  
Neeraj Gupta ◽  
Michael J. Hanley ◽  
David Kerstein ◽  
Meera Tugnait ◽  
Narayana Narasimhan ◽  
...  
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Renal Impairment ◽  
Protein Binding ◽  
Healthy Volunteers ◽  
Glomerular Filtration ◽  
Normal Renal Function ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Severe Renal Impairment

SummaryBackground Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, targets activated, mutant forms of ALK and overcomes mechanisms of resistance to the ALK inhibitors crizotinib, ceritinib, and alectinib. Brigatinib is approved in multiple countries for treatment of patients with ALK-positive non–small cell lung cancer. Based on population pharmacokinetic (PK) analyses, no dosage adjustment is required for patients with mild or moderate renal impairment. Methods An open-label, single-dose study was conducted to evaluate the PK of brigatinib (90 mg) in patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2; n = 8) and matched healthy volunteers with normal renal function (estimated glomerular filtration rate ≥ 90 mL/min/1.73 m2; n = 8). Plasma and urine were collected for the determination of plasma protein binding and estimation of plasma and urine PK parameters. Results Plasma protein binding of brigatinib was similar between patients with severe renal impairment (92 % bound) and matched healthy volunteers with normal renal function (91 % bound). Unbound brigatinib exposure (area under the plasma concentration-time curve from time zero to infinity) was approximately 92 % higher in patients with severe renal impairment compared with healthy volunteers with normal renal function. The renal clearance of brigatinib in patients with severe renal impairment was approximately 20 % of that observed in volunteers with normal renal function. Conclusions These findings support a brigatinib dosage reduction of approximately 50 % in patients with severe renal impairment.Trial registry: Not applicable.

Abstract 6277: Predictive Value of Estimated Glomerular Filtration Rate for Cardiovascular Events: The Treating to New Targets Study

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
James Shepherd ◽  
Chuan-Chuan Wun ◽  
Daniel J Wilson ◽  
Andrea L Zuckerman
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Cardiovascular Events ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Lipid Lowering ◽  
Final Visit ◽  
The Relationship ◽  
Dose Dependent

We previously demonstrated a dose-dependent improvement in renal function and reduction in cardiovascular risk in TNT with intensive lipid lowering with atorvastatin (ATV) 80 mg vs 10 mg. This post hoc analysis examines the relationship between the observed improvement in estimated glomerular filtration rate (eGFR) and reduction of major cardiovascular events (MCVE). After 8 weeks open-label therapy with ATV 10 mg, 10,001 patients with CHD were randomized to double-blind therapy with either ATV 10 or 80 mg. Patients were followed for a median of 4.9 years for the occurrence of MCVEs (CHD death, nonfatal MI, and stroke). The relationship between change from baseline eGFR (using the MDRD equation) at the final visit prior to a MCVE and the risk of MCVE was assessed using a Cox proportional hazards model adjusting for baseline eGFR and other baseline characteristics. Of 9656 patients with complete renal data, 156 had a MCVE before follow-up eGFR assessment and were excluded. In the remaining 9500 patients, mean baseline eGFR was 65.3 mL/min/1.73 m 2 and mean change from baseline was 4.3 mL/min/1.73 m 2 . This represented a reduction in the risk of MCVE of 2.7% per mL increase in eGFR (HR 0.973, 95% CI 0.967– 0.980, P <0.0001). This association remained significant in patients with eGFR <60 and those with eGFR ≥60 mL/min/1.73 m 2 at baseline, with no significant interaction between eGFR change and baseline renal status ( P =0.98). A 5 mL/min on-treatment improvement in eGFR was associated with a 12.6% reduction in MCVE, while a 5 mL/min reduction was associated with a 14.4% increase in MCVE. Mean change from baseline eGFR was 3.5 mL/min/1.73 m 2 with ATV 10 mg and 5.2 mL/min/1.73 m 2 with ATV 80 mg, representing significant 9.3% and 12.4% reductions in risk, respectively. Analysis of interaction between treatment and eGFR change for prediction of MCVE demonstrated a stronger association between eGFR change and MCVE in the ATV 80 mg treatment group ( P =0.011). Improvement in eGFR was highly associated with a reduction in MCVE, irrespective of baseline renal function. This relationship was dose dependent. Improvement in eGFR may be a biomarker for the response to atorvastatin, and for the stabilization of atherosclerotic cardiovascular disease.

scholarly journals Utility of saliva as a sample to assess renal function and estimated glomerular filtration rate

2016 ◽  
Vol 27 (2) ◽  
pp. 312 ◽  
Author(s):  
P. V. L. N.Srinivasa Rao ◽  
Naresh Yajamanam ◽  
KiranmayiS Vinapamula ◽  
V Sivakumar ◽  
AparnaR Bitla
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate

scholarly journals Renal function, complications, and outcomes of a reduction in tumor size after transarterial embolization for renal angiomyolipomas: a meta-analysis

2019 ◽  
Vol 47 (4) ◽  
pp. 1417-1428
Author(s):  
Letao Lin ◽  
Xinfei Li ◽  
Haitao Guan ◽  
Jian Wang ◽  
Xiaoqiang Tong ◽  
...  
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Tumor Size ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Meta Analysis ◽  
Transarterial Embolization ◽  
Nitrogen Levels ◽  
Significant Difference

Objective The present study aimed to evaluate renal function, complications, and changes in tumor size after transarterial embolization for patients with renal angiomyolipomas. Methods We performed a meta-analysis of transarterial embolization in patients with renal angiomyolipomas from January 1994 to April 2018. Endpoints of interest were the estimated glomerular filtration rate, serum creatinine levels, blood urea nitrogen levels, complications, and reduction of tumors. Results A total of 30 studies comprising 653 patients were included. A total of 32.0% of patients were treated by urgent transarterial embolization for spontaneous ruptured renal angiomyolipomas. Other patients sought to relieve symptoms or received embolism prophylactically. The estimated glomerular filtration rate showed no significant difference between before and after embolization. In 363 patients with data on complications, post-embolization syndrome occurred most frequently (54.0%). Only 16 (4.4%) patients had major complications. The diameter of sporadic angiomyolipomas was reduced by a mean of 2.09 cm (95% confidence interval [CI], 0.73–3.45 cm; I2 = 29.3%) and they were reduced in size by 30.0% (95% CI, 16.0%–44.0%; I2 = 27.9%). Conclusions Transarterial embolization of renal angiomyolipomas affects renal function preservation, with a low complication rate. Transarterial embolization is useful for sporadic and tuberous sclerosis complex-related angiomyolipomas.

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