Breaking News
August 21, 2018 - Clinical Trials Balance Out Urban, Rural Cancer Survival Rates
August 21, 2018 - New target found for treating thoracic aortic aneurysm
August 21, 2018 - Tumor cells’ ‘tells’ may allow some cancer patients to dodge unnecessary chemotherapy
August 21, 2018 - Dehydration changes shape and activity of the brain, reduces task performance
August 21, 2018 - Scientists discover peptides that can be used as new antibiotic candidates
August 21, 2018 - ‘Compulsivity circuit’ may drive alcohol-seeking behavior in heavy drinkers
August 21, 2018 - Type 2 diabetes on the rise among youngsters
August 21, 2018 - Genital warts may promote HIV sexual transmission
August 21, 2018 - Drop the C-word to reduce anxiety and overtreatment, say experts
August 21, 2018 - Kid-friendly MRI equipment has advantages for grown-ups, too
August 21, 2018 - Scleroderma Foundation names Tulane professor as ‘Doctor of the Year’
August 21, 2018 - Chagas disease causes chronic heart disease and has spread outside of Latin America
August 21, 2018 - FDA stirs debate by approving ‘natural’ app
August 21, 2018 - Clay may help fight disease-causing bacteria in wounds
August 21, 2018 - Emerging field of diabetology could address growing crisis in health care
August 21, 2018 - Experts examine stool protein biomarkers that indicate inflammatory bowel disease
August 21, 2018 - Orphazyme Announces Enrollment of First Patient in Phase III Clinical Trial of Arimoclomol for ALS
August 21, 2018 - Ovarian cancer cells hoard iron to fuel growth
August 21, 2018 - New Biodesign fellows will focus on vision care
August 21, 2018 - Prenatal DDT Exposure Associated with Greater Risk of Autism
August 21, 2018 - Cruciferous vegetables found to protect against colon cancer in mice
August 21, 2018 - New studies point to a promising future for bioengineered teeth
August 21, 2018 - ACR expresses concerns on step therapy in a recent meeting with HSS Secretary
August 21, 2018 - Gene therapy with telomerase does not increase cancer risk, study shows
August 21, 2018 - Ovarian cancer screening influenced by unconscious bias, study shows
August 21, 2018 - Scientists report novel gene therapy that halts vision loss in canine model of blinding disease
August 21, 2018 - RxBenefits introduces new tailored and flexible approach to managing hospital pharmacy benefits
August 21, 2018 - Motif Bio Announces FDA Acceptance of New Drug Application With Priority Review for Iclaprim for Treatment of Acute Bacterial Skin and Skin Structure Infections
August 21, 2018 - Google Glass helps kids with autism read facial expressions, study finds
August 21, 2018 - Thrombospondin-1 contributes to development of aortic aneurysm in mice and humans, study finds
August 21, 2018 - National Foundation for Cancer Research receives Safeway Foundation grant
August 21, 2018 - Protein aggregation in neurons linked to gene regulation in Huntington’s disease
August 21, 2018 - Aravive Biologics gains Fast Track Designation for AVB-S6-500 from U.S. FDA
August 21, 2018 - FDA Approves Opdivo (nivolumab) for Certain Patients with Previously Treated Small Cell Lung Cancer
August 21, 2018 - Success of blood test for autism affirmed
August 21, 2018 - Diabetic patients with disrupted sleep may need more time to heal their wounds
August 21, 2018 - AADE honors six educators for achievements in diabetes education
August 21, 2018 - Scientists find two molecules that may combat cancer and chronic infections
August 21, 2018 - Two Strategies for Preventing Diabetes in Minority Patients
August 21, 2018 - Living as a Gallbladder Cancer Survivor
August 21, 2018 - Can we predict the long-term outcome of boys with ADHD?
August 21, 2018 - GBCA creates model for developing scientist-advocate collaborations in cancer research
August 21, 2018 - Healthy diet could help promote healthy cellular aging in women
August 21, 2018 - Researchers develop gene expression predictor for immunotherapy response in melanoma
August 21, 2018 - Genome sequences of ape parasites provide insights on origin and early evolution of malaria
August 21, 2018 - MDI Biological Laboratory introduces Morris Scientific Discovery Fund for eligible research programs
August 21, 2018 - Pediatric brain tumor patients who undergo radiation less likely to recall recently experienced events
August 21, 2018 - Micro-flow model reveals complex interactions between the brain’s blood vessels and nerve cells
August 21, 2018 - Study investigates impact of osteoporosis on risk of developing dementia
August 21, 2018 - Federal method fails to detect most stores that sell cigarettes to minors
August 21, 2018 - Workers in open office seating have less stress than those in private offices and cubicles
August 21, 2018 - 1 in 4 in U.S. Has a Disability, CDC Reports
August 21, 2018 - Studies provide new insights into the role of sleep in chronic pain
August 21, 2018 - Study shows that rogue proteins may underlie some ALS and frontotemporal dementia cases
August 21, 2018 - Elevated LDL cholesterol levels linked to higher risk of CVD death in young, healthy people
August 21, 2018 - Measles cases on the rise in Europe
August 21, 2018 - CURE Media Group welcomes CancerCare to Strategic Alliance Partnership Program
August 21, 2018 - Blood management program associated with fewer transfusions in orthopedic patients
August 21, 2018 - Researchers create the world’s first artificial retina
August 21, 2018 - Yale researchers identify racial disparities in prescribing opioids for chronic pain
August 21, 2018 - BOOST-3 clinical trial aims to improve outcomes for severe TBI patients
August 21, 2018 - New study highlights Alzheimer’s herpes link, experts say
August 21, 2018 - Airline crew don’t have significantly elevated risk of thyroid cancer, new study finds
August 21, 2018 - States leverage federal funds to help insurers lower premiums
August 21, 2018 - New badge course explores research around skeletal muscle as an endocrine organ
August 21, 2018 - TG Therapeutics Announces Completion of Target Enrollment in the ULTIMATE Phase 3 Trials in Multiple Sclerosis
August 21, 2018 - Increased levels of human herpesvirus ID’d in Alzheimer’s
August 21, 2018 - To help patients quash pain, researcher develops practical guide for health care providers
August 20, 2018 - Medicine on the front line to be presented at Medical Innovation 2018
August 20, 2018 - Harbour Biomed and Kelun-Biotech collaborate to develop, commercialize anti-PD-L1 antibody
August 20, 2018 - The man who sold America on vitamin D — and profited in the process
August 20, 2018 - Finding the light in antimicrobials
August 20, 2018 - Unique pain program helps surgical patients wean off opioids safely and effectively
August 20, 2018 - Strawberries could mitigate colonic inflammation
August 20, 2018 - FDA Accepts New Drug Application (NDA) to Review Midazolam Nasal Spray, an Investigational Product for the Acute Treatment of Seizure Clusters
August 20, 2018 - Using Facebook to help young adults quit smoking
August 20, 2018 - ‘Liquid biopsy’ predicts lymphoma therapy success within days | News Center
August 20, 2018 - 5 Questions with Jordan Orange, Chair of Pediatrics
August 20, 2018 - New assay may help improve both sarcoma diagnosis and treatment
August 20, 2018 - New information on the brain regions related to metacognition, tactile sense
Bortezomib No Help for Kidney Transplant Rejection

Bortezomib No Help for Kidney Transplant Rejection

image_pdfDownload PDFimage_print

Action Points

  • Note that this small randomized trial found no evidence that the anti-plasma cell agent bortezomib is efficacious at reducing antibody-mediated rejection in kidney transplant.
  • Given the higher rate of adverse events in the bortezomib group, the future for the agent in this population does not look bright.

The proteasome inhibitor bortezomib (Velcade) failed to counteract late antibody-mediated rejection in kidney transplant patients, researchers reported from a small randomized trial.

In the placebo-controlled clinical study, overall graft survival at 2 years did not differ significantly between treatment arms and, in fact, numerically favored placebo (81% versus 96%; P=0.12). Patient survival also was no better with bortezomib than placebo (90% versus 100%, respectively; P=0.13), said Georg Böhmig, MD, of the Medical University of Vienna in Austria, and colleagues.

The trial’s primary endpoint, the change in estimated glomerular filtration rate (eGFR) over two years, was not significantly different between the treatment and placebo groups. The eGFR slope was -4.7 for the treatment group and -5.2 for placebo (difference 0.5; 95% CI -4.8 to 5.8; P=0.86), Böhmig and colleagues reported online in the Journal of the American Society of Nephrology.

The drug also had no apparent impact on donor-specific antibodies (DSA). Change in DSA at two years was not significantly different between the treatment and placebo groups, although substantial longitudinal variation of DSA in both groups made it difficult to detect a difference, the study authors reported.

Compounding the drug’s failure, overall adverse events were more common with bortezomib (91 versus 64) as were serious adverse events (10 versus 4). Bortezomib was associated with gastrointestinal toxicity, especially nausea and diarrhea. It was also associated with significantly higher grades of anemia, thrombocytopenia, and leukocytopenia, the study found.

“Our trial challenges the results of previous observational studies and argues against a beneficial effect of bortezomib as a treatment for late antibody-mediated rejection,” Böhmig and colleagues said. “The absence of an effect of bortezomib on DSA and disease activity is important because such effects would be expected, considering the known mechanism of action of the drug.”

Bortezomib, which is approved by the FDA for multiple myeloma and mantle cell lymphoma, promotes the apoptosis of plasma cells, they explained. However, “It is possible that the state of the plasma cells in late antibody-mediated rejection differs from that in other disease conditions in ways that render them less susceptible to the action of bortezomib,” they said.

The trial included 44 kidney transplant recipients diagnosed with late antibody-mediated rejection. They were randomized 1:1 to receive two cycles of either bortezomib or placebo at 3-month intervals in double-blinded fashion. Each treatment cycle consisted of bortezomib at 1.3 mg/m2, administered intravenously twice-weekly on days 1, 4, 8, and 11.

For antiviral prophylaxis, bortezomib-treated patients received oral valacyclovir at 500 mg/day for 3 weeks after initiation of each cycle. Patients in the control group received a 0.9% sodium chloride solution placebo, and instead of valacyclovir they received gelatin capsules filled with maltodextrin. Trial participants were followed for 24 months.

Despite the lack of efficacy reported in this trial, researchers should continue to explore the use of proteasome inhibitors to treat late antibody-mediated rejection of kidney transplants, Böhmig and colleagues said. “An interesting strategy to achieve a longer duration of inhibition and enhanced plasma cell depletion may be the use of new irreversible proteasome inhibitors, such as carfilzomib,” they said.

In addition, bortezomib may be more effective if combined with other agents or treatments, they suggested. “In this respect, the results of an ongoing trial designed to evaluate the effect of bortezomib as part of combinatorial treatment in late antibody-mediated rejection will be of interest,” they said. The Bortezomib in Rejection of Kidney Transplants (TRIBUTE) trial will assess the efficacy of bortezomib in combination with steroids, plasma exchange, and polyclonal intravenous immunoglobulins, according to clinicaltrials.gov.

Böhmig and colleagues noted some limitations to their trial, including using eGFR decline, the study’s main endpoint, as a surrogate of graft survival. However, “A study design to detect meaningful differences in survival rates would have necessitated a long-term multi-center trial including hundreds of patients. Even for our comparatively small trial, screening of more than 700 recipients was necessary for recruitment of less than 50 subjects eligible for the interventional part of the study,” they said.

The study was funded by the Austrian Science Fund and Sandoz GmbH, Austria.

No study authors reported relevant financial relationships.

  • Reviewed by
    F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner

1969-12-31T19:00:00-0500

last updated

Tagged with:

About author

Related Articles