Cemiplimab for Kidney Transplant Recipients With Advanced Cutaneous Squamous Cell Carcinoma

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 42(9), P. 1021 - 1030

Published: Jan. 22, 2024

PURPOSE Cemiplimab is approved for treating locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC). Solid organ transplant recipients have been excluded from immunotherapy trials, given concern allograft rejection despite their increased risk of skin cancers. Chronic immunosuppression necessary to prevent but may attenuate antitumor response with PD-1 inhibitors. METHODS We report a phase I study cemiplimab kidney (KTRs) CSCC. After cross-taper mammalian target rapamycin (mTOR) inhibitor and pulsed dose corticosteroids (prednisone 40 mg once daily, the day before on days 1-3 each cycle, followed by 20 daily 4-6, then 10 until subsequent cycle), patients received 350 intravenously every 3 weeks up 2 years were assessed 8 weeks. The primary end point was rate rejection, key secondary points including duration response, survival. RESULTS Twelve treated. No loss observed. A observed in five 11 evaluable (46%; 90% CI, 22 73), two durable responses beyond year. Median follow-up 6.8 months (range, 0.7-29.8). Treatment-related grade greater adverse events occurred (42%), diarrhea, infection, metabolic disturbances. One patient died angioedema anaphylaxis attributed mTOR cross-taper. CONCLUSION represent favorable immunosuppressive regimen KTRs CSCC receiving immunotherapy. This combination resulted no (funded Regeneron Pharmaceuticals [ClinicalTrials.gov identifier: NCT04339062 ]).

Language: Английский

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Clonal dynamics of alloreactive T cells in kidney allograft rejection after anti-PD-1 therapy

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 21, 2023

Abstract Kidney transplant recipients are at particular risk for developing tumors, many of which now routinely treated with immune checkpoint inhibitors (ICIs); however, ICI therapy can precipitate rejection. Here, we use TCR sequencing to identify and track alloreactive T cells in a patient melanoma who experienced kidney rejection following PD-1 inhibition. The treatment was associated sharp increase circulating CD8 + cell clones, display unique transcriptomic signature were also detected the rejected but not tumor sites. Longitudinal cross-tissue analyses indicate unintended expansion induced by cancer, coinciding ICI-associated organ

Language: Английский

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Fine-tuning tumor- and allo-immunity: advances in the use of immune checkpoint inhibitors in kidney transplant recipients

Clinical Kidney Journal, Journal Year: 2024, Volume and Issue: 17(4)

Published: March 8, 2024

Cancer is a common complication after kidney transplantation. Kidney transplant recipients (KTR) have 2- to 4-fold higher risk of developing cancer compared the general population and post-transplant malignancy third most cause death in KTR. Moreover, it well known that certain types are overrepresented transplantation, especially non-melanoma skin cancer. Immune checkpoint inhibitors (ICI) revolutionized treatment cancer, with remarkable survival benefit subgroup patients. ICI monoclonal antibodies block binding specific co-inhibitory signaling molecules. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), programmed cell protein 1 (PD-1), its ligand (PD-L1) main targets ICI. Solid organ (SOTR) been excluded from clinical trials owing concerns about tumor response, allo-immunity, rejection. Indeed, graft rejection has estimated as high 48% represents an emerging problem. The underlying mechanisms context poorly understood. search for restricted antitumoral responses without paramount importance. This review summarizes current knowledge use KTR, potential involved during treatment, biomarkers rejection, how deal practice.

Language: Английский

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Identifying Candidates for Immunotherapy among Patients with Non-Melanoma Skin Cancer: A Review of the Potential Predictors of Response

Journal of Clinical Medicine, Journal Year: 2022, Volume and Issue: 11(12), P. 3364 - 3364

Published: June 11, 2022

Non-melanoma skin cancer (NMSC) stands as an umbrella term for common cutaneous malignancies, including basal cell carcinoma (BCC) and squamous (cSCC), together with rarer cancers, such Merkel (MCC) other forms of adnexal cancers. The majority NMSCs can be successfully treated surgery or radiotherapy, but advanced metastatic stages may require systemic approaches immunotherapy immune checkpoint inhibitors (ICIs).

Language: Английский

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Immune suppression sustained allograft acceptance requires PD1 inhibition of CD8+ T cells

The Journal of Immunology, Journal Year: 2025, Volume and Issue: 214(1), P. 192 - 198

Published: Jan. 1, 2025

Abstract Organ transplant recipients require continual immune-suppressive therapies to sustain allograft acceptance. Although medication nonadherence is a major cause of rejection, the mechanisms responsible for graft loss in this clinically relevant context among individuals with preceding acceptance remain uncertain. Here, we demonstrate that skin mice maintained therapies, tacrolimus and mycophenolate, sensitizes hypofunctional PD1hi graft-specific CD8+ T cells. Uninterrupted therapy required because drug discontinuation triggers replicating requirement adherence recipients. Graft-specific cells allograft-accepted show diminished effector differentiation cytokine production, reciprocally increased PD1 expression. Allograft acceptance–induced expression essential, as PDL1 blockade reinvigorates cell activation ensuing rejection despite therapy. Thus, sustained inhibition essential by plus mycophenolate. This necessity sustaining explains high rates cancer administered immune checkpoint inhibitors targeting PD1/PDL1, highlighting shared suppression pathways exploited tumor current averting rejection.

Language: Английский

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Treatment of Merkel Cell Carcinoma in Organ Transplant Recipients - A Systematic Review

JAAD International, Journal Year: 2025, Volume and Issue: 19, P. 75 - 82

Published: Jan. 31, 2025

There are no clear treatment guidelines for solid organ transplantation (SOT) patients with Merkel cell carcinoma (MCC) despite increased incidence rates. To review outcomes of MCC prior SOT. A systematic (Prospective Register Systematic Reviews CRD42024569200) studies that reported modalities and SOT were selected. Databases screened included PubMed, Web Science, Scopus, Embase. Thirty articles comprising 21 case reports, 8 cohort studies, 1 clinical trial included. Treatment in reports trials surgery (77.7%), radiotherapy (62.9%), chemotherapy (25.9%), 3 receiving immune checkpoint inhibitors patient an oncolytic virus. Cohort varying usage surgery, radiotherapy, chemotherapy, immunosuppression regime modifications. Heterogeneity methodologies data reporting impeded meaningful comparisons. Lack stratification immunosuppressed populations the excluded reduced available comparison. Oncolytic virotherapy has potential to mediate a localized, targeted response minimal side effects patients. Inclusion into future involving immunotherapy combination therapies is needed establish guidelines.

Language: Английский

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Treatment with programmed-death-1 inhibitors for non-melanoma skin cancer among immunocompromised patients with subgroup analysis of solid organ transplant patients

The Oncologist, Journal Year: 2025, Volume and Issue: 30(2)

Published: Feb. 1, 2025

Programmed-cell death protein 1 (PD-1) inhibitors have emerged as a standard of care treatment among advanced-stage or metastatic cutaneous squamous cell carcinoma (cSCC). Immune-compromised patients and particularly solid organ transplant recipients (SOTRs) are considered at high risk for cSCC. When treated with PD-1 inhibitors, the possibility rejection, autoimmune flare, insufficient response to is feared. As these were excluded from past prospective clinical trials, we aim describe our institute's experience regarding patients. A retrospective analysis was conducted on cSCC inhibitors. Comparisons made between immune-compromised immune-competent groups, subgroup SOTR. The study cohort comprised 133 patients, including 97.8% receiving Cemiplimab mean age 77.2 ± 11.7 years. constituted 26.9% (n = 35) cohort, 10 SOTR (all kidney recipients). Objective rates (ORRs) disease control (DCR) comparable immunocompetent immunosuppressed (ORR: 76.8% vs 62.9%, P .12; DCR: 81.1% 68.6%, .13). demonstrated an 80% ORR DCR. Progression-free survival across all groups. Toxicity similar subgroups (68.6% 62.1%, .5). Two OTRs (20%) experienced acute graft rejection. demonstrate efficacy safety in While effective SOTR, requires multidisciplinary management due potential These findings provide valuable insights into this understudied population support use advanced

Language: Английский

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Combined standard immunosuppression and immune checkpoint inhibition for BKPyV+ metastatic renal cell carcinoma of the graft in a kidney transplant recipient with chronic rejection: a case report

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: March 17, 2025

We report on the first case of a dual-kidney transplant recipient diagnosed with metastatic BK polyomavirus-positive clear renal cell carcinoma sarcomatoid features, which caused extensive vena cava thrombosis. The patient was successfully treated immune checkpoint inhibitors (ICIs) ipilimumab plus nivolumab and continued immunosuppression tacrolimus, mycophenolate, steroids. He received ICIs despite presence graft dysfunction due to glomerulopathy. As expected, ICI treatment progressive but asymptomatic decline function, resulted in end-stage kidney disease. However, continuation full prevented acute rejection, intolerance syndrome episodes, or dual nephrectomy, enabled continue while dialysis achieve sustained partial remission at 17-month follow-up.

Language: Английский

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Immune checkpoint inhibitors use in lung transplant recipients: a case series and systematic review of literature

ESMO Open, Journal Year: 2025, Volume and Issue: 10(4), P. 104537 - 104537

Published: April 1, 2025

Immune checkpoint inhibitors (ICIs) are an innovative treatment that has improved long-term survival in several neoplastic diseases over the past decade. Solid organ transplant (SOT) recipients, particularly lung (LTx) have been largely excluded from clinical trials evaluating safety and efficiency of ICIs, because perceived high risk allograft rejection. In this study, we sought to evaluate use ICIs for all LTx patients French centers two Belgian centers. We found only a limited number cases which were suggested due lack alternative treatments. first case, acute respiratory failure death occurred, whereas second ICI was well tolerated resulted partial response. addition, presented case third patient whom considered but not used patient's comorbidities. This last highlights difficulty discussing risk-benefit balance, ultimately did favor patient. Further multicenter randomized controlled necessary investigate efficacy recipients.

Language: Английский

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Successful use of cemiplimab in a high immunologic risk kidney transplant recipient with metastatic squamous cell carcinoma

Transplant Immunology, Journal Year: 2025, Volume and Issue: unknown, P. 102242 - 102242

Published: May 1, 2025

Language: Английский

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