Does adding bortezomib to standard treatment improve late antibody-mediated rejection? — Multicenter randomized trial summary

A French multicenter randomized trial comparing standard therapy ± bortezomib showed no significant efficacy difference, but the combination group had more serious adverse events.[1]

Study type: Journal Article,Randomized Controlled Trial,Multicenter Study (category: randomized controlled trial) Published: Transplant international : official journal of the European Society for Organ Transplantation, 2026-09-23 Source: PubMed public abstract

A French multicenter randomized trial comparing standard therapy ± bortezomib showed no significant efficacy difference, but the combination group had more serious adverse events.[1]

Why this study matters

Why the study was done

Late active antibody-mediated rejection (late active AMR) with de novo donor-specific antibodies (de novo DSA) emerging after transplantation is an important clinical problem leading to chronic allograft injury and functional decline after kidney transplantation. bortezomib (a proteasome inhibitor) has been proposed to help reduce antibody production and improve AMR, but its efficacy and safety in human clinical trials remain unclear. This study was conducted in multiple centers in France with a randomized, open-label design to evaluate the efficacy and safety of adding bortezomib to standard therapy (corticosteroids, plasmapheresis, intravenous immunoglobulin) [1].

What the study actually found

Main findings (based on the abstract report)

• Study period and participants: February 2015 to July 2019, adult kidney transplant recipients diagnosed with late active AMR and accompanied by de novo DSA; sixty patients were randomized 1:1.
• Intervention: Control group received standard therapy; experimental group received bortezomib in addition to standard therapy (two courses, each course four infusions).
• Primary composite endpoint (12 months): reduction of immunodominant DSA mean fluorescence intensity by >50% and stability or improvement of microvascular inflammation and glomerular (graft) lesions on biopsy.
• Intention-to-treat (ITT) analysis: achieved primary endpoint in bortezomib group 40.0% vs standard therapy group 33.3% (RR = 1.20, 95% CI 0.61–2.34; p = 0.59).
• Per-protocol analysis: bortezomib group 50.0% vs control 42.1% (RR = 1.19, 95% CI 0.60–2.36; p = 0.62).
• Components of the composite endpoints (DSA reduction, histopathological improvement) did not differ significantly between groups.
• Safety: serious adverse events occurred more frequently in the bortezomib group, 23 patients (76.7%) vs control group 14 patients (46.7%), p = 0.017.[1]

Possible implications for CKD, dialysis, or transplant patients

What this means for kidney transplant patients and families

The abstract of this study indicates that in patients with late active AMR accompanied by de novo DSA, adding bortezomib to standard therapy did not show a statistically significant efficacy benefit, but was associated with a higher rate of serious adverse events. This suggests that in similar cases, bortezomib is not an established adjunctive therapy with confirmed net benefit; safety considerations are particularly important. The above describes the study report results and is not medical advice; clinical treatment choices should be made by the treating transplant team based on individual circumstances and the latest evidence.[1]

Current study limitations

Study limitations (based on this abstract)

• This summary is based only on the public abstract; the full text was not reviewed, so more methodological details (e.g., randomization method, baseline characteristics, loss to follow-up, long-term follow-up) cannot be examined.
• The abstract did not provide full details of sample stratification or subgroup analyses, nor complete long-term kidney function or survival outcome data.
• The open-label design may influence certain judgments or reported outcomes, but the abstract did not specify how bias was controlled.
• A single trial result does not represent a consensus; this summary should not be taken as clinical practice guidance.[1]

This article was written based on the PubMed public abstract and the full text was not reviewed.

Which conclusions remain uncertain

Unresolved or hypothetical aspects

• Whether specific patient subgroups (for example by DSA type, renal histopathologic subtype, or background immunosuppression) might benefit from bortezomib is not supported by sufficient evidence in the abstract.
• Whether long-term kidney function preservation, graft survival, or mortality would be affected by short-term addition of bortezomib cannot be confirmed due to lack of long-term outcome data in the abstract.
• The mechanisms by which bortezomib led to more serious adverse events, or whether dose or dosing-interval adjustments could reduce risk, remain unproven.

The above points are associations shown by the study or unproven hypotheses and should not be directly inferred as causal or as standard practice.

Questions to discuss with your medical team

• Are the results of this study applicable to my case? (Please bring the abstract or have a physician assess applicability)
• Has my transplant team used bortezomib in similar situations? What efficacy and adverse effects did they observe?
• If considering adding a medication, what are alternative options and how do their risks compare?
• What types of serious adverse events were reported in the study? How might they affect quality of life or subsequent treatments?
• Are there ongoing or larger follow-up studies that provide more safety and long-term outcome data?

How to read this study (our interpretation)

This section was written by the Beyond CKD editor — a kidney-transplant recipient with a health-management background, not a physician — using only the PubMed abstract. We have not read the full paper, and no clinician has reviewed this text. It is meant to help you understand the numbers, not to advise treatment.

What the study asked

Late active antibody-mediated rejection (AMR) with new donor-specific antibodies (dnDSA) is a leading cause of kidney-transplant loss, and standard treatment — steroids, plasmapheresis and intravenous immunoglobulin — has limited effect. Bortezomib, a proteasome inhibitor originally used for multiple myeloma, kills the plasma cells that make antibodies and had been proposed as an add-on. This French multicentre, randomised, open-label trial tested that idea.

How to read the results

The primary endpoint was a composite: at 12 months, a greater than 50% fall in the dominant DSA signal and stable or improved microvascular inflammation and transplant glomerulopathy on biopsy. Results: 40.0% reached it with bortezomib versus 33.3% with standard care alone — RR 1.20, 95% CI 0.61–2.34, p = 0.59. An interval stretching from 0.61 to 2.34 means “could be better, could be worse; we cannot tell.” The per-protocol analysis (50.0% vs 42.1%) was equally inconclusive. Harm, however, was clear: serious adverse events occurred in 76.7% of the bortezomib group versus 46.7% of controls (p = 0.017). In short, no visible benefit and a clear increase in harm.

Limitations

The trial planned 100 patients but stopped at 60, so it was underpowered — “no significant difference” could mean no effect or too few patients to see one. The direction of the harm signal, however, is unambiguous. The open-label design may have influenced how adverse events were recorded. Follow-up was 12 months; long-term graft survival is not reported.

What it means for readers and people with kidney disease

For transplant recipients, the message is direct: current randomised evidence does not support adding bortezomib to routine treatment of late AMR, and it clearly increases side effects. If you have been told you have dnDSA or AMR, treatment choices remain difficult — but “negative” trials like this matter, because they spare patients the toxicity of a drug without proof.

How to check further

Ask your transplant team: Am I being monitored for DSA? If AMR were diagnosed, what treatment would you recommend today, and are there clinical trials I could consider?

Original abstract: PubMed 42846119 (https://pubmed.ncbi.nlm.nih.gov/42846119/). Interpretation last updated 2026-11-06.

References

[1] Snanoudj R, Marquant F, Renaudin K, Dubois V, Koenig A, Arzouk N. Bortezomib in combination with standard-of-care for late active antibody-mediated rejection with de novo donor-specific antibodies after kidney transplantation: a multicenter randomized trial.. Transplant international : official journal of the European Society for Organ Transplantation. 2026. DOI: 10.3389/ti.2026.16702. PMID: 42846119.

Medical disclaimer: This article is for general health education and information only. It does not constitute individual medical diagnosis, treatment advice, or a doctor–patient relationship. Medical research is continually updated, and study findings have their own scope and limitations. Every patient's condition, laboratory values, medications and treatment needs differ. Do not stop or adjust medication doses, change your diet or fluid intake, or alter dialysis or transplant treatment based on this article alone. For any medical questions, please consult your nephrologist or another qualified healthcare professional.

Article created: 2026-10-16 | Original study published: 2026-09-23 | Last checked: 2026-10-16 (source metadata cross-checked with PubMed)