Comparing Bortezomib to Traditional Therapies for Antibody-Mediated Rejection (AMR): Out with the Old?
| Autor: | Daniel Cruz, B. Kubak, A. Baas, T. Khuu, M. Allareddy, Elaine F. Reed, Mario C. Deng, A. Ardehali, R.K. Cheng, A. Hickey, Richard J. Shemin, Eugene C. DePasquale, Michael C. Fishbein, A. Nsair, C. Holt, Martin Cadeiras, M.H. Kwon |
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| Rok vydání: | 2013 |
| Předmět: |
Pulmonary and Respiratory Medicine
Transplantation medicine.medical_specialty Ejection fraction business.industry Bortezomib Incidence (epidemiology) medicine.medical_treatment Antibody titer Urology Surgery law.invention Randomized controlled trial law Antibody mediated rejection Medicine Rituximab Plasmapheresis Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | The Journal of Heart and Lung Transplantation. 32:S110 |
| ISSN: | 1053-2498 |
| DOI: | 10.1016/j.healun.2013.01.229 |
| Popis: | Purpose Novel therapies are emerging for treatment of AMR, but minimal data is available comparing efficacy and safety with prevailing treatments. We tested whether the efficacy of bortezomib (Bzb) in lowering donor antibody antibodies (DSA) was improved over standard plasmapheresis (PP)/ IVIG or rituximab therapy for AMR. Methods and Materials Ten adult heart transplant recipients with DSA mean fluorescence intensity (MFI) >1000, biopsy-proven, and/or clinically suspicious AMR were treated for 20 episodes between February 2010 to August 2012. Treatment consisted of PP (5 days) with IVIG (2 g/kg), rituximab (375 mg/m²), and/or Bzb (0.7-1 mg/m² x 4) at least 30 days apart. Antibody titers were measured via single antigen Luminex® assay before and after therapy. Parametric and non-parametric comparisons, linear and logistic regression were used as appropriate to assess outcomes. Results There was a greater reduction in DSA with Bzb therapy (beta=0.58, 95% CI 0.16-0.90, p=0.01) when adjusting for time to AMR. In those with compromised ejection fraction, there was improvement after Bzb therapy (p=0.03). Patient survival in both groups was 100% at 60 days. Conclusions Compared to PP/IVIG or rituximab, Bzb was more effective in reducing DSA without a significant effect on the incidence of infection or survival in this limited data set. There is indication for a randomized controlled trial comparing Bzb to standard AMR therapies to help determine clinical and survival benefit. Patient Characteristics Other (n=11) Bortezomib (n=10) p-value PTD at AMR 427.9 ± 417.6 1610.2 ± 2470.4 0.13 DSA MFI at AMR 6966.4 ± 5231.2 7282.0 ± 5874.9 0.90 DSA MFI post-therapy 6419.9 ± 4515.5 5100.8 ± 5754.5 0.56 % MFI decrease 0.00 ± 0.37 0.37 ± 0.52 0.05 Cylex 493.7 ± 190.5 580.4 ± 159.5 0.31 Allograft Dysfunction 36.4% 60.0% 0.40 EMB + 72.7% 70.0% 0.89 VAD 72.7% 60.0% 0.66 Late AMR 36.4% 50.0% 0.67 Infection 54.5% 50.0% 0.84 |
| Databáze: | OpenAIRE |
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