Kidney retransplantation after anti–programmed cell death-1 (PD-1)–related allograft rejection

Lipson, Evan J.; Naqvi, Fizza; Loss, Manisha J.; Schollenberger, Megan D.; Pardoll, Drew M.; Moore, Jack; Brennan, Daniel C.

doi:10.1111/ajt.15856

Cited by 22 publications

(23 citation statements)

References 20 publications

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“…Retransplantation after ICI-related kidney rejection also is possible if sustained cancer remission is successfully achieved. 22 To our knowledge, sustainable or replacement therapies in patients with other organ transplants remain nonexistent. Regardless, the use of ICIs after solid organ transplantation should not be discouraged, especially in patients with limited options, and the potential risk of organ complications should not be considered prohibitive.…”

Section: Discussionmentioning

confidence: 99%

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Clinical outcomes of solid organ transplant recipients with metastatic cancers who are treated with immune checkpoint inhibitors: A single‐center analysis

Owoyemi

Vaughan

Costello

et al. 2020

Cancer

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BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, but to the authors' knowledge, limited data exist regarding the safety and efficacy of these agents in transplant recipients. Herein, the authors have reported their experience with 17 patients who were treated with ICIs for metastatic malignancies after undergoing solid organ transplantation. METHODS: Data were abstracted for solid organ transplant recipients who received ICIs for the treatment of malignancy between January 1, 2016, and September 30, 2019. The authors identified 7 kidney, 8 liver, and 2 heart transplant recipients. Outcomes of interest were adverse drug reactions, cancer progression, and patient survival. RESULTS: The most common malignancies treated with ICIs were metastatic squamous cell carcinoma (5 patients; 29%) and hepatocellular carcinoma (5 patients; 29%), which were noted exclusively among liver transplant recipients. The median duration on ICIs was 1.7 months (interquartile range, 0.4-7.6 months). Five patients (29%) developed adverse reactions, including 4 patients (24%) with immune-related adverse events(irAEs), 3 patients (18%) with acute allograft rejections, 1 patient (6%) with autoimmune colitis, and 1 patient (6%) with ICI-induced cardiotoxicity (the patient was a heart transplant recipient). The cumulative incidence of cancer progression was 50% and 69%, respectively, at 6 months and 12 months. Eleven patients (65%) died over the median follow-up period of 4.6 months (interquartile range, 1.5-13.2 months) from the time of ICI initiation, with cancer progression being the most common cause of death. CONCLUSIONS: ICIs can be used as individualized therapy in selected patients who have undergone solid organ transplantation but more studies are needed to determine how best to use these agents to improve outcomes further. Cancer 2020;126:4780-4787.

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Section: Discussionmentioning

confidence: 99%

“…Kidney transplant recipients have the option of undergoing dialysis after allograft failure. Retransplantation after ICI‐related kidney rejection also is possible if sustained cancer remission is successfully achieved 22 . To our knowledge, sustainable or replacement therapies in patients with other organ transplants remain nonexistent.…”

Section: Discussionmentioning

confidence: 99%

Clinical outcomes of solid organ transplant recipients with metastatic cancers who are treated with immune checkpoint inhibitors: A single‐center analysis

Owoyemi

Vaughan

Costello

et al. 2020

Cancer

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“…Management of these patients is complex and often multidisciplinary, where AlloSure can provide additional, previously lacking, information about the allograft. This was recently demonstrated in a case report by Lipson et al [16] in the management of a renal transplant recipient (RTR) on checkpoint inhibitors to treat malignancy.…”

Section: Introductionmentioning

confidence: 86%

Transition of Renal Patients Using AlloSure Into Community Kidney Care (TRACK): Protocol for Long-Term Allograft Surveillance in Renal Transplant Recipients

et al. 2021

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Background Patients with end-stage kidney disease require complex and expensive medical management. Kidney transplantation remains the treatment of choice for end-stage kidney disease and is considered superior to all other modalities of renal replacement therapy or dialysis. However, access to kidney transplant is limited by critical supply and demand, making it extremely important to ensure longevity of transplanted kidneys. This is prevented through lifelong immunosuppression, with caution not to overly suppress the immune system, resulting in toxicity and harm. Transition of care to community nephrologists after initial kidney transplantation and monitoring at a transplant center is an important process to ensure delivery of effective and patient-centric care closer to home. Once transplanted, laborious surveillance of the immune system and monitoring for potential rejection and injury are undertaken through an armamentarium of screening modalities. Posttransplant surveillance for kidney function and injury remains key to follow-up care. While kidney function, quantified by estimated glomerular filtration rate and serum creatinine, and kidney injury, measured by proteinuria and hematuria, are standard biomarkers used to monitor injury and rejection posttransplant, they have recently been demonstrated to be inferior in performance to that of AlloSure (CareDx Inc, Brisbane, CA) circulating donor-derived, cell-free DNA (dd-cfDNA). Objective The outcomes and methods of monitoring renal transplant recipients posttransplant have remained stagnant over the past 15 years. The aim of this study is to consider intensive surveillance using AlloSure dd-cfDNA in an actively managed protocol, assessing whether it increases long-term allograft survival in kidney transplant recipients compared with current standard clinical care in community nephrology. Methods The study protocol will acquire data from a phase IV observational trial to assess a cohort of renal transplant patients managed using AlloSure dd-cfDNA and patient care managers versus 1000 propensity-matched historic controls using United Network for Organ Sharing U.S. Scientific Registry of Transplant Recipients data. Data will be managed in a centralized electronic data server. The primary outcome will be superior allograft survival, as a composite of return to dialysis, retransplant, death due to allograft failure, and death with a functional graft (infection, malignancy, and cardiovascular death). The secondary endpoints will assess improved kidney function through decline in estimated glomerular filtration rate and immune activity through development of donor-specific antibodies. Results The total sample is anticipated to be 3500 (2500 patients managed with AlloSure dd-cfDNA and 1000 propensity-matched controls). Active enrollment began in November 2020. Conclusions Based on a significant literature base, we believe implementing the surveillance of dd-cfDNA in the kidney transplant population will have a positive impact on graft survival. Through early identification of rejection and facilitating timely intervention, prolongation of allograft survival versus those not managed by dd-cfDNA surveillance protocol should be superior. International Registered Report Identifier (IRRID) PRR1-10.2196/25941

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“…Verschiedene Veröffentlichungen berichten über Fälle von Patienten mit fortgeschrittenem cSCC, die erfolgreich mit Pembrolizumab behandelt wurden. Lipson et al beschrieben den Fall eines nierentransplantierten Patienten mit metastasiertem cSCC, der mit Pembrolizumab (2 mg/kg alle 3 Wochen) behandelt wurde [70, 71]. Der Patient erreichte eine CR, entwickelte jedoch nach 2 monatiger Pembrolizumab-Therapie eine akute Allotransplantatabstoßung, so dass im weiteren Verlauf die Niere entfernt werden musste.…”

Section: Icb Bei Cscc: Wie Ist Die Derzeitige Evidenzlage?unclassified

“…Mehrere Fallberichte zeigten jedoch, dass Cemiplimab in der Vergangenheit erfolgreich bei Empfängern von Organtransplantaten eingesetzt wurde (Tabelle 1). Die Ergebnisse sprechen dafür, dass die ICB bei diesen Patienten wirksam ist, und eine vorherige immunsuppressive oder Prednison-Medikation scheint die antitumorale Reaktion während der ICB nicht zu beeinträchtigen [58, 71, 92]. Allerdings fehlen auch für diese Patientengruppe qualitativ hochwertige Belege, und die Evidenzlage zur Wirksamkeit ist auf anekdotische Berichte beschränkt.…”

Section: Icb Bei Speziellen Untergruppen Von Cscc-patienten: Organtransplantatempfänger Patienten Mit Malignen Hämatologischen Erkrankungunclassified

Immun-Checkpoint-Blockade bei fortgeschrittenem kutanen Plattenepithelkarzinom: Was wissen wir derzeit im Jahr 2020?

et al. 2021

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Das kutane Plattenepithelkarzinom (cSCC) ist der zweithäufigste Hautkrebs und entsteht vor allem in chronisch sonnengeschädigter Haut. Nachgewiesene Hauptrisikofaktoren sind Immunsuppression, genetische Störungen wie Xeroderma pigmentosum (XP), Exposition gegenüber bestimmten Medikamenten und Umweltnoxen. Therapie der Wahl bei cSCC ist die chirurgische Entfernung, die im Frühstadium meist kurativ erfolgt. Einige wenige Patienten entwickeln jedoch lokal fortgeschrittene Tumoren oder Fernmetastasen, die nach wie vor schwierig zu behandeln sind. Die auf CTLA-4, PD-L1 und PD-1 ausgerichtete Immun-Checkpoint-Blockade (ICB) hat die onkologische Therapie und insbesondere die Behandlung von Hautkrebserkrankungen als Tumoren mit hoher Mutationslast sehr stark verändert. In der vorliegenden Übersichtsarbeit liegt der Fokus auf den Unterschieden zwischen dem kutanen Plattenepithelkarzinom und dem kutanen Melanom (CM) sowie den damit verbundenen Implikationen für die Therapie. Darüber hinaus werden die aktuelle Evidenzlage zur ICB für die Behandlung des fortgeschrittenem cSCC zusammengefasst und die Chancen und Risiken dieser therapeutischen Option für diese Krebsentität erörtert. Ferner richten wir das Augenmerk auf spezielle interessierende Subgruppen von Patienten wie etwa Organtransplantatempfänger, Patienten mit malignen hämatologischen Erkrankungen, XP und Feldkanzerisierung.

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Kidney retransplantation after anti–programmed cell death-1 (PD-1)–related allograft rejection

Cited by 22 publications

References 20 publications

Clinical outcomes of solid organ transplant recipients with metastatic cancers who are treated with immune checkpoint inhibitors: A single‐center analysis

Clinical outcomes of solid organ transplant recipients with metastatic cancers who are treated with immune checkpoint inhibitors: A single‐center analysis

Transition of Renal Patients Using AlloSure Into Community Kidney Care (TRACK): Protocol for Long-Term Allograft Surveillance in Renal Transplant Recipients

Immun-Checkpoint-Blockade bei fortgeschrittenem kutanen Plattenepithelkarzinom: Was wissen wir derzeit im Jahr 2020?

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