TY - JOUR
T1 - A multi-center study on safety and efficacy of immune checkpoint inhibitors in cancer patients with kidney transplant
AU - Immune Checkpoint Inhibitors in Solid Organ Transplant Consortium
AU - Murakami, Naoka
AU - Mulvaney, Patrick
AU - Danesh, Melissa
AU - Abudayyeh, Ala
AU - Diab, Adi
AU - Abdel-Wahab, Noha
AU - Abdelrahim, Maen
AU - Khairallah, Pascale
AU - Shirazian, Shayan
AU - Kukla, Aleksandra
AU - Owoyemi, Itunu O.
AU - Alhamad, Tarek
AU - Husami, Samir
AU - Menon, Madhav
AU - Santeusanio, Andrew
AU - Blosser, Christopher D.
AU - Zuniga, Sandra Carias
AU - Soler, Maria Jose
AU - Moreso, Francesc
AU - Mithani, Zain
AU - Ortiz-Melo, David
AU - Jaimes, Edgar A.
AU - Gutgarts, Victoria
AU - Lum, Erik
AU - Danovitch, Gabriel M.
AU - Cardarelli, Francesca
AU - Drews, Reed E.
AU - Bassil, Claude
AU - Swank, Jennifer L.
AU - Westphal, Scott
AU - Mannon, Roslyn B.
AU - Shirai, Keisuke
AU - Kitchlu, Abhijat
AU - Ong, Song
AU - Machado, Shana M.
AU - Mothi, Suraj S.
AU - Ott, Patrick A.
AU - Rahma, Osama
AU - Hodi, F. Stephen
AU - Sise, Meghan E.
AU - Gupta, Shruti
AU - Leaf, David E.
AU - Devoe, Craig E.
AU - Wanchoo, Rimda
AU - Nair, Vinay V.
AU - Schmults, Chrysalyne D.
AU - Hanna, Glenn J.
AU - Sprangers, Ben
AU - Riella, Leonardo V.
AU - Jhaveri, Kenar D.
N1 - Funding Information:
The authors thank Dino Mazzarelli, JD, from Partners Healthcare Research Management, for his assistance coordinating data use agreement with each institution. NM is supported by K08DK120868 from the National Institute of Diabetes and Digestive Kidney Diseases and by the Carl W. Gottschalk Research Scholar Grant from the American Society of Nephrology Foundation for Kidney Research. MES is supported by K23DK117014 from the National Institute of Diabetes and Digestive Kidney Diseases . EAJ is supported by National Institutes of Health P30CA008748 , R01DK114321 , R01FP00008739 , and DM180384 . BS is a senior clinical investigator for The Research Foundation Flanders (to Fonds Wetenschappelijk Onderzoek-Vlaanderen; 1842919N). LVR is supported by R01AI143887 from the National Institutes of Allergy and Infectious Diseases and is the Harold and Ellen Danser Endowed/Distinguished Chair in Transplantation at Massachusetts General Hospital. The authors thank Matthew A. Sparks, MD, for reviewing the visual abstract.
Funding Information:
The authors thank Dino Mazzarelli, JD, from Partners Healthcare Research Management, for his assistance coordinating data use agreement with each institution. NM is supported by K08DK120868 from the National Institute of Diabetes and Digestive Kidney Diseases and by the Carl W. Gottschalk Research Scholar Grant from the American Society of Nephrology Foundation for Kidney Research. MES is supported by K23DK117014 from the National Institute of Diabetes and Digestive Kidney Diseases. EAJ is supported by National Institutes of Health P30CA008748, R01DK114321, R01FP00008739, and DM180384. BS is a senior clinical investigator for The Research Foundation Flanders (to Fonds Wetenschappelijk Onderzoek-Vlaanderen; 1842919N). LVR is supported by R01AI143887 from the National Institutes of Allergy and Infectious Diseases and is the Harold and Ellen Danser Endowed/Distinguished Chair in Transplantation at Massachusetts General Hospital. The authors thank Matthew A. Sparks, MD, for reviewing the visual abstract. A part of the study was presented as an oral abstract in the Kidney Week 2020 Reimagined. NM, PM, MD, GJH, RW, CED, LVR, and KDJ conceived of and designed the study. All authors were responsible for the collection and assembly of data. NM, PM, MD, SSM, GJH, RW, CED, LVR, and KDJ performed the data analysis and interpretation. All authors participated in writing the manuscript. All authors gave final approval of the manuscript. All authors are accountable for all aspects of the work.
Publisher Copyright:
© 2020 International Society of Nephrology
PY - 2021/7
Y1 - 2021/7
N2 - Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and overall survival were assessed in cutaneous squamous cell carcinoma and melanoma, the most common cancers in our cohort, and compared with stage-matched 23 patients with squamous cell carcinoma and 14 with melanoma with a kidney transplant not receiving ICIs. Following ICI treatment, 29 out of 69 (42%) patients developed acute rejection, 19 of whom lost their allograft, compared with an acute rejection rate of 5.4% in the non-ICI cohort. Median time from ICI initiation to rejection was 24 days. Factors associated with a lower risk of rejection were mTOR inhibitor use (odds ratio 0.26; 95% confidence interval, 0.09-0.72) and triple-agent immunosuppression (0.67, 0.48-0.92). The objective response ratio was 36.4% and 40% in the squamous cell carcinoma and melanoma subgroups, respectively. In the squamous cell carcinoma subgroup, overall survival was significantly longer in patients treated with ICIs (median overall survival 19.8 months vs. 10.6 months), whereas in the melanoma subgroup, overall survival did not differ between groups. Thus, ICIs were associated with a high risk of rejection in patients with kidney transplants but may lead to improved cancer outcomes. Prospective studies are needed to determine optimal immunosuppression strategies to improve patient outcomes.
AB - Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and overall survival were assessed in cutaneous squamous cell carcinoma and melanoma, the most common cancers in our cohort, and compared with stage-matched 23 patients with squamous cell carcinoma and 14 with melanoma with a kidney transplant not receiving ICIs. Following ICI treatment, 29 out of 69 (42%) patients developed acute rejection, 19 of whom lost their allograft, compared with an acute rejection rate of 5.4% in the non-ICI cohort. Median time from ICI initiation to rejection was 24 days. Factors associated with a lower risk of rejection were mTOR inhibitor use (odds ratio 0.26; 95% confidence interval, 0.09-0.72) and triple-agent immunosuppression (0.67, 0.48-0.92). The objective response ratio was 36.4% and 40% in the squamous cell carcinoma and melanoma subgroups, respectively. In the squamous cell carcinoma subgroup, overall survival was significantly longer in patients treated with ICIs (median overall survival 19.8 months vs. 10.6 months), whereas in the melanoma subgroup, overall survival did not differ between groups. Thus, ICIs were associated with a high risk of rejection in patients with kidney transplants but may lead to improved cancer outcomes. Prospective studies are needed to determine optimal immunosuppression strategies to improve patient outcomes.
KW - immune checkpoint inhibitors
KW - kidney transplant
KW - onconephrology
KW - rejection
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U2 - 10.1016/j.kint.2020.12.015
DO - 10.1016/j.kint.2020.12.015
M3 - Article
C2 - 33359528
AN - SCOPUS:85102755593
VL - 100
SP - 196
EP - 205
JO - Kidney international
JF - Kidney international
SN - 0085-2538
IS - 1
ER -