Pilot evaluation of PD-1 inhibition in metastatic cancer patients with a history of liver transplantation: The Mayo Clinic experience

Thomas T. DeLeon, Marcela A. Salomao, Bashar A. Aqel, Mohamad B. Sonbol, Raquel T. Yokoda, Ahmad H. Ali, Adyr A. Moss, Amit Mathur, David M. Chascsa, Jorge Rakela, Alan H Bryce, Mitesh J Borad

Research output: Contribution to journalArticle

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Abstract

Background: Patients with solid organ transplants (SOTs) have been excluded from programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitor clinical trials due to concern for allograft rejection. The use of immune checkpoint inhibitor therapy remains controversial in transplant patients. Methods: A retrospective pilot evaluation was conducted to assess the safety and efficacy of PD-1 inhibitors in patients with liver transplantation (LT). The primary endpoint was the rate of allograft rejection. Secondary endpoints included overall response rate (ORR), progression free survival (PFS) and overall survival (OS). Translational objectives included evaluation of tumor PD-L1, tumor infiltrating lymphocytes (TILs) and allograft PD-L1 expression. Results: Seven metastatic cancer patients with a history of LT who received PD-1 inhibitor therapy were included [hepatocellular carcinoma (HCC), n=5; melanoma, n=2]. Rejection was observed in 2 of 7 patients. When rejection occurs it appears to be an early event with a median time to rejection of 24 days in our cohort. One patient achieved a complete response (CR), 3 patients had progressive disease (PD) and 3 patients discontinued therapy prior to restaging assessments. Two of five patients with available tissue had PD-L1 expression in the allograft and both developed rejection. One of five evaluable patients had abundant TILs. Two of five evaluable patients had PD-L1 tumor staining. The single patient with both abundant TILs and PD-L1 staining obtained a response. The median OS and PFS were 1.1 (0.3–21.1) and 1.8 (0.7–21.1) months, respectively. Conclusions: In this pilot evaluation both preliminary efficacy (1 of 4) and allograft rejection (2 of 7) were exhibited in evaluable patients. Larger, prospective trials are needed to elucidate optimal patient selection.

Original languageEnglish (US)
Pages (from-to)1054-1062
Number of pages9
JournalJournal of Gastrointestinal Oncology
Volume9
Issue number6
DOIs
StatePublished - Dec 1 2018

Fingerprint

Liver Transplantation
Neoplasms
Proteins
Allografts
Ligands
Tumor-Infiltrating Lymphocytes
Disease-Free Survival
Staining and Labeling
Transplants
Survival
Patient Selection
Hepatocellular Carcinoma
Melanoma
Therapeutics
Clinical Trials
Safety

Keywords

  • Graft rejection
  • Hepatocellular carcinoma (HCC)
  • Immunotherapy
  • Liver transplantation (LT)
  • Melanoma

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

Cite this

Pilot evaluation of PD-1 inhibition in metastatic cancer patients with a history of liver transplantation : The Mayo Clinic experience. / DeLeon, Thomas T.; Salomao, Marcela A.; Aqel, Bashar A.; Sonbol, Mohamad B.; Yokoda, Raquel T.; Ali, Ahmad H.; Moss, Adyr A.; Mathur, Amit; Chascsa, David M.; Rakela, Jorge; Bryce, Alan H; Borad, Mitesh J.

In: Journal of Gastrointestinal Oncology, Vol. 9, No. 6, 01.12.2018, p. 1054-1062.

Research output: Contribution to journalArticle

DeLeon, Thomas T. ; Salomao, Marcela A. ; Aqel, Bashar A. ; Sonbol, Mohamad B. ; Yokoda, Raquel T. ; Ali, Ahmad H. ; Moss, Adyr A. ; Mathur, Amit ; Chascsa, David M. ; Rakela, Jorge ; Bryce, Alan H ; Borad, Mitesh J. / Pilot evaluation of PD-1 inhibition in metastatic cancer patients with a history of liver transplantation : The Mayo Clinic experience. In: Journal of Gastrointestinal Oncology. 2018 ; Vol. 9, No. 6. pp. 1054-1062.
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abstract = "Background: Patients with solid organ transplants (SOTs) have been excluded from programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitor clinical trials due to concern for allograft rejection. The use of immune checkpoint inhibitor therapy remains controversial in transplant patients. Methods: A retrospective pilot evaluation was conducted to assess the safety and efficacy of PD-1 inhibitors in patients with liver transplantation (LT). The primary endpoint was the rate of allograft rejection. Secondary endpoints included overall response rate (ORR), progression free survival (PFS) and overall survival (OS). Translational objectives included evaluation of tumor PD-L1, tumor infiltrating lymphocytes (TILs) and allograft PD-L1 expression. Results: Seven metastatic cancer patients with a history of LT who received PD-1 inhibitor therapy were included [hepatocellular carcinoma (HCC), n=5; melanoma, n=2]. Rejection was observed in 2 of 7 patients. When rejection occurs it appears to be an early event with a median time to rejection of 24 days in our cohort. One patient achieved a complete response (CR), 3 patients had progressive disease (PD) and 3 patients discontinued therapy prior to restaging assessments. Two of five patients with available tissue had PD-L1 expression in the allograft and both developed rejection. One of five evaluable patients had abundant TILs. Two of five evaluable patients had PD-L1 tumor staining. The single patient with both abundant TILs and PD-L1 staining obtained a response. The median OS and PFS were 1.1 (0.3–21.1) and 1.8 (0.7–21.1) months, respectively. Conclusions: In this pilot evaluation both preliminary efficacy (1 of 4) and allograft rejection (2 of 7) were exhibited in evaluable patients. Larger, prospective trials are needed to elucidate optimal patient selection.",
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author = "DeLeon, {Thomas T.} and Salomao, {Marcela A.} and Aqel, {Bashar A.} and Sonbol, {Mohamad B.} and Yokoda, {Raquel T.} and Ali, {Ahmad H.} and Moss, {Adyr A.} and Amit Mathur and Chascsa, {David M.} and Jorge Rakela and Bryce, {Alan H} and Borad, {Mitesh J}",
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T1 - Pilot evaluation of PD-1 inhibition in metastatic cancer patients with a history of liver transplantation

T2 - The Mayo Clinic experience

AU - DeLeon, Thomas T.

AU - Salomao, Marcela A.

AU - Aqel, Bashar A.

AU - Sonbol, Mohamad B.

AU - Yokoda, Raquel T.

AU - Ali, Ahmad H.

AU - Moss, Adyr A.

AU - Mathur, Amit

AU - Chascsa, David M.

AU - Rakela, Jorge

AU - Bryce, Alan H

AU - Borad, Mitesh J

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Background: Patients with solid organ transplants (SOTs) have been excluded from programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitor clinical trials due to concern for allograft rejection. The use of immune checkpoint inhibitor therapy remains controversial in transplant patients. Methods: A retrospective pilot evaluation was conducted to assess the safety and efficacy of PD-1 inhibitors in patients with liver transplantation (LT). The primary endpoint was the rate of allograft rejection. Secondary endpoints included overall response rate (ORR), progression free survival (PFS) and overall survival (OS). Translational objectives included evaluation of tumor PD-L1, tumor infiltrating lymphocytes (TILs) and allograft PD-L1 expression. Results: Seven metastatic cancer patients with a history of LT who received PD-1 inhibitor therapy were included [hepatocellular carcinoma (HCC), n=5; melanoma, n=2]. Rejection was observed in 2 of 7 patients. When rejection occurs it appears to be an early event with a median time to rejection of 24 days in our cohort. One patient achieved a complete response (CR), 3 patients had progressive disease (PD) and 3 patients discontinued therapy prior to restaging assessments. Two of five patients with available tissue had PD-L1 expression in the allograft and both developed rejection. One of five evaluable patients had abundant TILs. Two of five evaluable patients had PD-L1 tumor staining. The single patient with both abundant TILs and PD-L1 staining obtained a response. The median OS and PFS were 1.1 (0.3–21.1) and 1.8 (0.7–21.1) months, respectively. Conclusions: In this pilot evaluation both preliminary efficacy (1 of 4) and allograft rejection (2 of 7) were exhibited in evaluable patients. Larger, prospective trials are needed to elucidate optimal patient selection.

AB - Background: Patients with solid organ transplants (SOTs) have been excluded from programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitor clinical trials due to concern for allograft rejection. The use of immune checkpoint inhibitor therapy remains controversial in transplant patients. Methods: A retrospective pilot evaluation was conducted to assess the safety and efficacy of PD-1 inhibitors in patients with liver transplantation (LT). The primary endpoint was the rate of allograft rejection. Secondary endpoints included overall response rate (ORR), progression free survival (PFS) and overall survival (OS). Translational objectives included evaluation of tumor PD-L1, tumor infiltrating lymphocytes (TILs) and allograft PD-L1 expression. Results: Seven metastatic cancer patients with a history of LT who received PD-1 inhibitor therapy were included [hepatocellular carcinoma (HCC), n=5; melanoma, n=2]. Rejection was observed in 2 of 7 patients. When rejection occurs it appears to be an early event with a median time to rejection of 24 days in our cohort. One patient achieved a complete response (CR), 3 patients had progressive disease (PD) and 3 patients discontinued therapy prior to restaging assessments. Two of five patients with available tissue had PD-L1 expression in the allograft and both developed rejection. One of five evaluable patients had abundant TILs. Two of five evaluable patients had PD-L1 tumor staining. The single patient with both abundant TILs and PD-L1 staining obtained a response. The median OS and PFS were 1.1 (0.3–21.1) and 1.8 (0.7–21.1) months, respectively. Conclusions: In this pilot evaluation both preliminary efficacy (1 of 4) and allograft rejection (2 of 7) were exhibited in evaluable patients. Larger, prospective trials are needed to elucidate optimal patient selection.

KW - Graft rejection

KW - Hepatocellular carcinoma (HCC)

KW - Immunotherapy

KW - Liver transplantation (LT)

KW - Melanoma

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