Kidney transplant despite poor initial conditions: New drug sustainably reduces immune response against donor organ

An international research team led by the Medical University of Vienna reports on a new treatment strategy that has made a kidney transplant possible for a patient with no realistic chance of receiving a suitable donor organ. As the case study demonstrates for the first time, the use of a new drug from the field of cancer medicine can achieve a substantial and sustained reduction in antibodies against potential transplants, a level not previously attained. This significantly improves the prospects of a successful organ transplant even in cases with a particularly unfavourable initial immunological profile. The results have recently been published in the highly respected New England Journal of Medicine and could open up new perspectives in transplant medicine.

The new drug Teclistamab is currently used to treat blood cancer (myeloma). It specifically eliminates those cells in the blood and bone marrow that produce antibodies against foreign structures. Due to this unique mechanism of action, the substance has now also come to the attention of transplant medicine: the research team led by Georg Böhmig and Martina Schatzl (Clinical Department of Nephrology and Dialysis, Department of Medicine III, MedUni Vienna) applied it for the first time as part of a case study in a dialysis-dependent patient with a highly unfavourable initial immunological profile.
 
The 37-year-old had developed particularly pronounced HLA sensitisation following two previous kidney transplants. In this process, the immune system produces antibodies against tissue markers of potential donor organs, known as HLA (Human Leukocyte Antigens). These antibodies significantly limit the availability of suitable organs. In the specific case of the study, the calculated probability (cPRA value) of ever finding a compatible donor kidney for the patient was actually zero. Consequently, the study participant’s name had been on the waiting list for more than twelve years, whilst his condition progressively deteriorated.

Successful transplant after 31 weeks of therapy
Treatment with teclistamab over a period of 31 weeks turned the tide: the drug achieved such a substantial and sustained reduction in antibodies against tissue antigens as is not possible with the methods currently available for HLA sensitisation. “During the course of therapy, HLA markers from donor kidneys, against which there had previously been strong antibody reactions, were gradually classified as acceptable,” reports lead author Martina Schatzl. Eventually, a suitable organ was found and successfully transplanted. “The patient is doing very well today; his kidney function is excellent, and he no longer needs dialysis,” adds study leader Georg Böhmig.

Further studies on benefits and risks needed
20 to 30 per cent of patients on the waiting list for donor kidneys are affected by significant HLA sensitisation, some of whom have no chance of receiving a suitable organ. Existing procedures for so-called desensitisation aim to reduce the number of antibodies prior to transplantation, but are only effective to a limited extent and for a short period.
The treatment approach described in the case study, by contrast, directly intervenes in antibody production and sustainably reduces the immune response over a longer period. “This could herald a paradigm shift in transplant medicine and open up new prospects for a group of patients who have been particularly disadvantaged until now,” says Böhmig.
 
Detailed immunological results from the current case study also suggest that the new treatment strategy might also be applicable in xenotransplantation – that is, the transplantation of organs from genetically modified pigs – as well as in blood-group-incompatible transplants. “Looking ahead, an extension to other forms of organ transplantation, such as heart transplantation, as well as use in the post-transplant setting to treat antibody-mediated rejection reactions, also seems conceivable,” says Böhmig. However, before the new treatment strategy can be used in clinical practice, its benefits and risks must be systematically investigated. A study of this kind is already being planned at MedUni Vienna.