J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://jocmr.elmerjournals.com

Review

Volume 16, Number 12, December 2024, pages 571-577

Clinical Implications of Skin Cancer in Kidney Transplant Recipients in the Era of Immune Checkpoint Inhibitors

**Table 1.** Food and Drug Administration-Approved Indications of CPIs in Skin Cancer Patients
Drug	Target	Indications	Year of approval
SCC: squamous cell carcinoma; BCC: basal cell carcinoma; CPIs: checkpoint inhibitors; CTLA-4: cytotoxic T lymphocyte associated protein 4; PD-1: programmed cell death protein 1; PD-L1: programmed cell death ligand 1; LAG-3: lymphocyte activation gene 3.
Ipilimumab	CTLA-4	Melanoma	2011
Nivolumab	PD-1	Melanoma, SCC of head and neck	2014
Pembrolizumab	PD-1	Melanoma, Merkel cell carcinoma, cutaneous SCC	2014
Atezolizumab	PD-L1	Melanoma	2016
Avelumab	PD-L1	Merkel cell carcinoma	2017
Cemiplimab	PD-1	Cutaneous SCC, BCC	2019
Relatlimab	LAG-3	Melanoma	2022

Table 1. Food and Drug Administration-Approved Indications of CPIs in Skin Cancer Patients

Drug

Target

Indications

Year of approval

SCC: squamous cell carcinoma; BCC: basal cell carcinoma; CPIs: checkpoint inhibitors; CTLA-4: cytotoxic T lymphocyte associated protein 4; PD-1: programmed cell death protein 1; PD-L1: programmed cell death ligand 1; LAG-3: lymphocyte activation gene 3.

Ipilimumab

CTLA-4

Melanoma

2011

Nivolumab

PD-1

Melanoma, SCC of head and neck

2014

Pembrolizumab

PD-1

Melanoma, Merkel cell carcinoma, cutaneous SCC

2014

Atezolizumab

PD-L1

Melanoma

2016

Avelumab

PD-L1

Merkel cell carcinoma

2017

Cemiplimab

PD-1

Cutaneous SCC, BCC

2019

Relatlimab

LAG-3

Melanoma

2022

**Table 2.** Prospective Studies of CPIs in KTRs With Skin Cancers
Study	Schenk et al, 2024 [26]	Hanna et al, 2024 [24]
KTRs: kidney transplant recipients; SCC: squamous cell carcinoma; CPIs: checkpoint inhibitors; dd-cfDNA: donor-derived cell-free DNA; IV: intravenous; TRAL: treatment-related allograft loss; TRAE: treatment-related adverse event; mTORi: mammalian target of rapamycin inhibitor.
Number of KTRs enrolled	8	12
Median age	66	62
Cancers included	Advanced melanoma (1), cutaneous SCC (5), Merkel cell carcinoma (2)	Advanced cutaneous SCC
CPIs used	Nivolumab (480 mg IV every 4 weeks) in all patients initially, in six out of eight patients with disease progression, ipilimumab (IPI) (1 mg/kg, IV) + nivolumab (NIVO) (3 mg/kg IV every 3 weeks, four times), followed by NIVO	Cemiplimab (350 mg IV every 3 weeks)
Median time from transplantation to start of CPIs	13 years	7.2 years
Primary endpoint	Disease control rate (complete response (CR), partial response (PR), or stable disease), allograft loss at 16 weeks	Rejection or allograft loss
Median follow-up time	9.1 months	6.8 months
Safety outcomes	Three of eight patients experienced TRAL; excluding TRAL, no grade 3 or higher TRAE related to IPI + NIVO.	No patients had rejection or allograft. TRAE occurred in 83% (grade 3 or higher in 42%).
dd-cfDNA	Performed every 2 weeks in all patients and weekly if rising; increased 10 - 15 days before rise in serum creatinine.	Performed in five patients at baseline and after cemiplimab; minor increase in only one.
Conclusions	Tacrolimus and prednisone decrease tumor response with no protection on rejection.	Cemiplimab had a response rate similar to general population, and use of mTORi along with pulse-dose steroids had acceptable safety profile and rejection rate.

Table 2. Prospective Studies of CPIs in KTRs With Skin Cancers

Study

Schenk et al, 2024 [26]

Hanna et al, 2024 [24]

KTRs: kidney transplant recipients; SCC: squamous cell carcinoma; CPIs: checkpoint inhibitors; dd-cfDNA: donor-derived cell-free DNA; IV: intravenous; TRAL: treatment-related allograft loss; TRAE: treatment-related adverse event; mTORi: mammalian target of rapamycin inhibitor.

Number of KTRs enrolled

Median age

Cancers included

Advanced melanoma (1), cutaneous SCC (5), Merkel cell carcinoma (2)

Advanced cutaneous SCC

CPIs used

Nivolumab (480 mg IV every 4 weeks) in all patients initially, in six out of eight patients with disease progression, ipilimumab (IPI) (1 mg/kg, IV) + nivolumab (NIVO) (3 mg/kg IV every 3 weeks, four times), followed by NIVO

Cemiplimab (350 mg IV every 3 weeks)

Median time from transplantation to start of CPIs

13 years

7.2 years

Primary endpoint

Disease control rate (complete response (CR), partial response (PR), or stable disease), allograft loss at 16 weeks

Rejection or allograft loss

Median follow-up time

9.1 months

6.8 months

Safety outcomes

Three of eight patients experienced TRAL; excluding TRAL, no grade 3 or higher TRAE related to IPI + NIVO.

No patients had rejection or allograft. TRAE occurred in 83% (grade 3 or higher in 42%).

dd-cfDNA

Performed every 2 weeks in all patients and weekly if rising; increased 10 - 15 days before rise in serum creatinine.

Performed in five patients at baseline and after cemiplimab; minor increase in only one.

Conclusions

Tacrolimus and prednisone decrease tumor response with no protection on rejection.

Cemiplimab had a response rate similar to general population, and use of mTORi along with pulse-dose steroids had acceptable safety profile and rejection rate.