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Immune checkpoint inhibitors might be used for organ transplant patients under special very controlled circumstances.
Malignancy is a significant adverse event in solid organ transplant recipients (SOTR). The risk of developing cancer has been reported to be 2- and 4-fold higher compared to the general population.
Immune checkpoint inhibitors (ICI) have revolutionized the treatment of cancer, with remarkable survival benefit. However, SOTR have been excluded from clinical trials owing to concerns about organ rejection and immunosuppressive therapy. The only evidence for the use of ICI in SOTR is based on case reports and small case series. Since the indications of ICI are expected to expand, it is important to determine risk-benefit of the use of ICI in patients with SOTR.
1. Efficacy of ICI in organ transplant recipients.
The disease control rate varies between 21% for liver transplants and 45% for kidney transplant recipients suffering from diverse cancer types1. Overall response rate has been evaluated around 47% in different SOTR cancer patients3 which seems to be similar to non SOTR patients. The most interesting cancer types for this approach are melanoma (BRAF WT or BRAF mutant after progression on BRAF/MEK inhibition) and squamous cell carcinoma of the skin as non-immunotherapeutic options are almost non existing for these patients. In general ICI should only be initiated after failure of local therapy including surgery and/or radiation and/or previous systemic therapy. Best tumor response rates have been observed in patients on methylprednisolone (<10mg) monotherapy3.
2. Risk of graft rejection and graft loss
The risk of kidney graft rejection may be as high as 48%, the risk of liver graft rejection 37% and the risk of heart transplant rejection 20%. Graft rejection is mostly accompanied by graft failure (81% of patients). It seems that graft rejection occurs early after ICI initiation with a median of 21 days and mostly in patients on methylprednisolone monotherapy. Allograft rejection seems independent of the ICI used (anti-PD-1 or anti-CTLA-4)1,2,3,4. The risk of death due to rejection has been reported to be as high as 14%. However rejection is not the most frequent cause of death in these populations4.
3. Treatment of graft rejection
Almost all patients suffering from rejection have been treated with high dose corticosteroids, along with ICI discontinuation. Addition of other immunosuppressants (mycophenolate mofetil, tacrolimus, intravenous immunoglobulines) had with poor success-rate1,2,3,4.
Based on the limited data available in the literature in the absence of controlled trials, we can conclude that there is a reasonable response rate after initiation of ICI. This is at the expense of an increased risk of rejection and graft loss. The highest rejection rate was found in kidney transplant patients followed by liver and heart transplant recipients. As biomarkers for kidney graft rejection and/or tumor response are mostly lacking, initiation and continuation of ICI in transplant patients should be based on a multidisciplinary decision and a thourough conversation with the patient and his relatives. Because treatment with ICI may be life-saving it should be considered in patients with SOTR.
T. Van Meerhaeghe1, S. Aspeslagh2,3, A. Le Moine1
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