Fewer effective options exist for kidney transplant recipients with late antibody-mediated rejection (AMR), particularly those who have already undergone multiple prior therapies. At the 2026 American Transplant Congress (ATC), Aylin Akifova, MD, a physician-researcher in the Department of Nephrology at Charité University Berlin, presented a post hoc analysis of a phase 2 felzartamab study, Felzartamab, an Anti-CD38 Antibody, in Late AMR: Efficacy Independent of Prior Rejection History or Therapy. The analysis showed that a prior history of rejection or desensitization did not diminish responsiveness to the CD38 monoclonal antibody. We spoke with Dr. Akifova about what the findings reveal for this challenging patient population and what comes next.
This transcript has been edited for clarity.
For those who missed your presentation at ATC, could you briefly highlight the key findings of your post hoc analysis?
The aim of this study was to better understand the immunologic profile of the patients who were included in the phase two felzartamab study for AMR. What we did for this post hoc analysis was to go back and review the immunologic history of the patients who were included. We wanted to better understand and review all alloimmune events such as previous projection episodes, donor-specific antibodies, and desensitization and treatments that were performed before the study inclusion and before felzartamab exposure in those patients.
Then we compared whether the response to felzartamab in terms of reduction of the microvascular inflammation score, reduction of molecular activity, and the biomarker assessments showed any difference. We saw that the results were comparable and the response to felzartamab was equal in those groups regardless of their previous rejection presence or history of previous AMR treatments.
Did any findings from your analysis surprise you?
Yes, we were surprised by how treatment experienced this group of patients was. We saw that half of the patients had some desensitization or AMR therapy in some form and beyond treatments that we know as part of the standard of care regimen—plasmapheresis, IVIG [intravenous immunoglobulin], or B-cell-depleting agents. We observed that a substantial portion of these patients also were invited to participate in interventional AMR studies. So, they have also received some treatments within investigational AMR studies, which shows us that this was not a treatment-naive cohort, but rather patients who had some longstanding rejection that was difficult to treat. But still, we were surprised that even this group showed pretty significant treatment effects.
Results from your analysis and the larger study were promising but the trial size was small. Do you think that these results will hold up in a larger phase 3 trial?
The efficacy we observed in the phase 2 trial was actually a secondary finding. The primary end point of the phase 2 trial was to confirm the safety profile but the positive efficacy results that we observed encouraged us to also conduct a phase 2 extension trial where the patients from phase 2 who had some relapse of AMR activity or the placebo patients had the chance to receive treatment with felzartamab. I think the phase 3 trial of course will confirm if this efficacy really holds among a much larger and more heterogeneous cohort of patients. So, we are very excited about the phase 3 results.
Apart from overall general efficacy, are there any specific questions that you’re hoping a phase 3 trial will answer?
Yes, phase 3 of course has to meet the primary end point of efficacy, which is defined as the biopsy-proven histologic resolution of AMR at follow-up biopsy after a fixed treatment regimen. However, I also think that it’s very important for the phase 3 study to confirm the favorable safety profile that we observed earlier in the phase 2 study. I think those are the two big findings that we will look at in phase 3. I also think that it will be interesting to see if the secondary outcomes, such as the biomarker assessments, still behave in the same way in this study design.
What is the current status of the phase 3 trial?
The phase 3 study is called TRANSCEND. This is an active, ongoing study, and the recruitment target was met. Recruitment was just completed
When we spoke with Georg Böhmig after Kidney Week last autumn, he mentioned that the mechanism of action for CD38-targeted therapies isn’t fully understood. How important is it to better understand this to guide felzartamab’s future use?
I think we still have not fully decoded the mechanism of action of CD38 antibodies in AMR.
However, the phase 2 study and also the phase 2 extension were an immense learning opportunity for us to better understand how the agents work. The readout of the molecular response and of the biomarker results helped us understand that the NK [natural killer] cells that are known to be the direct injury mediators in AMR play some significant role.
The reduction of NK cells after treatment was paralleled by a significant reduction in donor-derived cell-free DNA levels. I think those two findings indicate some signal that NK cells are the direct injury mediators. Whereas we did not observe, at least in phase 2—which of course was a small study—a clear, direct effect on donor-specific antibodies, even though we would expect them to show a significant decrease.
The decline in donor-derived cell-free DNA shows us that, in treating AMR, we should care about injury control. For future use, the data indicate that we can make use of those biomarkers, especially donor-derived cell-free DNA, to serve as a companion biomarker to CD38 therapies and also maybe help clinicians guide some treatment decisions, which will be relevant when the drugs are actually in clinical practice use.