- 68 year old patient
- 07/2018 squamous cell carcinoma (SCC) of the head
- initial tumor stage: cT4 cN0 M0, G3
- p53 mutation, PDL1 expression: 25%, 70% in recurrent tumor (06/2020)
- 07/2018 extirpation
- 03 - 07/2019 resection of recurrent tumor
- 12/2019 local progression
- 06/2020 PET-CT: Metastases of bones (t1, t4, l3, l4, os ilii), lymph nodes (regional, hilar, mediastinal) and pleural metastases
- kidney transplantation in 2012 (end-stage kidney disease caused by IgA nephropathy)
- immunosuppressive therapy with tacrolimus (5mg 1-0-0), everolimus (1,5mg 1-0-1) and prednisolone (2,5mg 1-0-0 every second day)
- since 05/2020: everolimus monotherapy (0,5mg 1-0-0)
- 11/2019 bleomycin-based electrochemotherapy, local progression
- 12/2020 radiotherapy, cumulative dose of 60 Gy, local progression and distant metastases
- 06/2020 Cetuximab (6 cycles), Carboplatin (1 cycle), mixed response
- 09/2020 Cemiplimab (5 cycles) à acute transplant rejection, partial response
After five cycles of Cemiplimab the patient presented with skin rash and an acute deterioration of the kidney function.
Because a transplant rejection was suspected, high-dose systemic corticosteroid therapy was initiated (1 mg/kg bw/day for seven days, followed by 0,5 mg/kg bw/day for seven days). Additionally, topical corticosteroids were used for the exanthema. Everolimus was continued without interruption.
Immunotherapy was interrupted. The systemic corticosteroid therapy quickly led to stabilisation of the kidney function. While maintaining the immunosuppressive therapy with everolimus in the same dosage, the therapy with cemiplimab was continued. A PET-CT showed partial response and fortunately recently ongoing stable disease. Kidney function has been stable since then.
Long-term immunosuppression is associated with a higher risk of malignancy. The decision whether to start an immunotherapy in patients with organ transplantation is complex due to potential induction of organ rejection and only limited data on predictive factors. A retrospective analysis of 64 case reports shows that the risk for a graft rejection might depend on the transplanted organ, with the highest graft rejection rate in renal allografts (44% vs. 39 % in liver and 20% in cardiac allografts). Patients who were treated with PD-1 inhibitors showed higher rates of allograft rejection compared to those who were treated with CTLA-4 inhibitors (39% vs. 23%, Kumar et al., Oncologist, 2020). Despite the immunosuppression with everolimus, cemiplimab checkpoint inhibitor therapy induced a tumor response in this heavily pretreated patient. In a retrospective analysis Abdel-Wahab et al. found that low-dose prednisolone therapy was associated with a high risk for graft rejection, whereas calcineurin inhibitors were associated with a worse tumor response (Abdel-Wahabet al. Journal for ImmunoTherapyof Cancer, 2019). A preclinical study showed that the combination of checkpoint- inhibitors with mTor inhibitors potentiates the anti-tumor immunity (Langdon et al., Oncoimmunology, 2018), suggesting a potentially beneficial combination in organ transplant patients. Further investigation and prospective clinical trials are needed to evaluate how immunotherapy can be optimized in organ transplant patients.
