Redefining the future of post-transplant care with personalized immunosupression

In this guest editorial, Dr. Richard Knight, medical director of transplant diagnostics at Thermo Fisher Scientific discusses the importance of developing advanced, personalized immunosuppressive therapies and diagnostics in transplantation. Knight highlights innovations such as gene profiling assays and urine-based biomarker tests for early detection of rejection, advocating for less invasive monitoring techniques. Knight also emphasizes the need for safer, less toxic immunosuppressive drugs and improved post-transplant care, to enhance patient outcomes, quality of life, and treatment compliance.

For patients facing organ failure, transplantation often represents the best – and sometimes only – hope for survival. Yet the very therapies needed to protect the new organ following a transplant carry substantial risks. These immunosuppressive drug regimens can open patients up to an array of negative side effects, including heightened susceptibility to infection, metabolic complications and even cancer.

Persisting with a “one-size-fits-all” approach to post-transplant immunosuppression can further compound those challenges. Standardized protocols often overlook individual patient needs, such as differences in age, genetics and existing comorbidities that may impact drug effectiveness, inviting under or overimmunosuppression and compromising outcomes.

No two people are alike, and neither are their immune responses. Developing immunosuppressive strategies that reflect this diversity is paramount to ensuring the most successful outcomes for transplant patients, not only in length of life but also quality of life.

Barriers in post-transplant care

Transplantation is a lifelong journey requiring lifelong care. This includes the long-term use of immunosuppressive drugs to help reduce the risk of organ rejection. Immunosuppressants work by tempering the immune system’s response to the transplanted organ; paradoxically, a strong immune system response is vital in helping the body prevent infections and identify and destroy abnormal cells with the potential to become cancerous.

Currently, there are no tests available to precisely measure an individual’s level of immunosuppression. As a result, patients are often managed with broad over-immunosuppression, which can lead not only to infections and disease but also to direct toxicity of the organ.

To enable truly personalized immunosuppressive drug therapies in the future, we must develop and leverage next-generation technologies that can capture real-time dynamics of immunosuppression, providing actionable measurements that guide dose, timing and drug selection.

The role of transplant diagnostics

Diagnostics play a critical role throughout the transplant journey and in the future, may play an even bigger role in managing immunosuppression. One of the primary uses of transplant diagnostics is to help reduce the risk of rejection. Prior to transplant, high-resolution HLA typing and antibody testing are used to enable more precise donor-recipient matches. The closer the match between donor and recipient, the less likely the recipient is to mount an immune response that would attack the donated organ.

That said, every individual’s immune system is unique, and historically it has been difficult, if not impossible, to predict how likely a patient is to experience rejection. Recently, a new pre-transplant risk assessment assay was introduced that may help change that paradigm. This new assay can provide information about a patient’s risk of early acute rejection based on their unique gene profile prior to transplant. Tests like this may help clinicians make more informed decisions about post-transplant management and better balance the risk of rejection against the adverse effects of immunosuppression.

Following a transplant, patients must continue to undergo regular monitoring to ensure their new organ is functioning properly. Historically, much of this monitoring has relied on biopsies, long considered the “gold standard” for diagnosing and confirming rejection. However, biopsies are invasive, subject to interpretation and may not detect rejection until significant damage has already occurred.

Minimally invasive diagnostic methods that can help detect signs of rejection earlier are needed to enable more personalized immunosuppression protocols. One recent innovation in this space is urine-based CXCL10 biomarker testing. Multiple clinical studies have shown that elevated levels of the CXCL10 chemokine in the urine are associated with inflammation and early graft dysfunction, demonstrating that minimally invasive tests can deliver answers clinicians need while sparing patients the pain and invasiveness of a biopsy.

The future of post-transplant care

Ensuring transplant recipients have the best chance to live a long and healthy life depends not only on developing more personalized immunosuppressive drug approaches that are tailored to their immune systems and conditions, but also safer, less toxic medications.

While long known to many of us in the transplant space, this need was further highlighted in a study that was recently published in the American Journal of Transplantation discussing the substantial treatment burden that is related to immunosuppression side effects as well as concerns about long-term medication safety. The findings display the widespread challenge of these drug regimens that are overshadowed by the risks of acute rejection. Struggles with post-transplant care related to immunosuppression point to the need for further research into post-transplant immunosuppressive care and monitoring.

As an industry, we should envision a future where patients benefit from less invasive diagnostics, more personalized immunosuppression regimens and less toxic medications. These advances could improve transplantation success rates and quality of life for transplant recipients, as well as increase compliance with post-transplant treatment.