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1.
Cancers (Basel) ; 13(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34638395

RESUMO

Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The application of oncology, transplant medicine, and surgery to improve patients' survival and quality of life is the core of transplant oncology. Hepatobiliary malignancies have been treated by liver transplantation (LT) with significant improved outcome. In addition, as the liver is the most common site of metastasis for colorectal cancer (CRC), patients with CRC who have stable unresectable liver metastases are good candidates for LT, and initial studies have shown improved survival compared to palliative systemic therapy. The indications of LT for hepatobiliary malignancies have been slowly expanded over the years in a stepwise manner; however, they have only been shown to improve patient survival in the setting of limited systemic therapy options. This review illustrates the concept and history of transplant oncology as an evolving field for the management of hepatocellular carcinoma, intrahepatic biliary cancer, and liver-only metastasis of non-hepatobiliary carcinoma. The utility of immunotherapy in the transplant setting is discussed as well as the feasibility of using circulating tumor DNA for surveillance post-transplantation.

2.
J Immunother Cancer ; 9(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34625513

RESUMO

BACKGROUND: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. METHODS: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. RESULTS: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. CONCLUSIONS: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

3.
Oncoimmunology ; 10(1): 1927313, 2021 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-34104543

RESUMO

Background: The incidence of renal immune-related adverse events (irAEs) is reported to be 3.8%, with varied definitions of acute kidney injury (AKI). This study reports a 10-year experience at MD Anderson Cancer Center of patients diagnosed with melanoma and treated with immune checkpoint inhibitors (ICIs) and evaluated the incidence of AKI, associated factors, and its association with overall survival. Methods: A retrospective chart review (2010-2019) of all patients with melanoma treated with ipilimumab, nivolumab, pembrolizumab, or atezolizumab was performed. All available serum creatinine data were extracted and used to calculate the estimated GFR (eGFR) using the CKD Epi equation, and to diagnose AKI using the two KDIGO (Kidney Disease: Improving Global Outcomes) criteria for defining stage I AKI in 1664 unique patients. Cumulative incidence rates of AKI after initiation of ICIs were calculated in the presence of death as a competing risk. The effects of covariates on the cumulative incidence function of AKI were evaluated in a univariant and multivariable analysis. Overall survival was estimated by Kaplan-Meier method in accordance to the occurrence of AKI. Results: The incidence of AKI by definitions 1a and 1b were 3.49% and 3.33%, respectively. After adjudication, AKI attributable to ICI was 58% and 65% of the overall incidence of AKI in each definition respectively. Increasing age was associated with decreased risk of AKI. Asian race was associated with a higher risk of AKI. Comorbidities were not associated with increased risk of AKI while use of proton pump inhibitors (PPI), ipilimumab or ICI combinations were significantly associated with AKI. AKI was not significantly associated with overall survival. Immune-related adverse events (irAEs) occurred in 30% of patients with AKI but their incidence was not different in patients with AKI attributable to ICI versus other AKI. Conclusions: In a large population of patients with melanoma treated with ICIs, an accurate documentation of AKI in setting of ICI use and predictors associated is presented. AKI following ICI use is infrequent, not associated with mortality, and associated with the use of ipilimumab, ICI combinations and PPIs.


Assuntos
Injúria Renal Aguda , Melanoma , Injúria Renal Aguda/induzido quimicamente , Humanos , Inibidores de Checkpoint Imunológico , Incidência , Melanoma/tratamento farmacológico , Estudos Retrospectivos
4.
J Clin Oncol ; 39(24): 2710-2719, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-33929874

RESUMO

PURPOSE: BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication of allogenic hematopoietic stem cell transplantation (AHSCT), particularly in recipients of alternative donor transplants, which are being performed in increasing numbers. BKV-HC typically results in painful hematuria, urinary obstruction, and renal dysfunction, without a definitive therapeutic option. METHODS: We performed a clinical trial (ClinicalTrials.gov identifier: NCT02479698) to assess the feasibility, safety, and efficacy of administering most closely HLA-matched third-party BKV-specific cytotoxic T lymphocytes (CTLs), generated from 26 healthy donors and banked for off-the-shelf use. The cells were infused into 59 patients who developed BKV-HC following AHSCT. Comprehensive clinical assessments and correlative studies were performed. RESULTS: Response to BKV-CTL infusion was rapid; the day 14 overall response rate was 67.7% (40 of 59 evaluable patients), which increased to 81.6% among evaluable patients at day 45 (40 of 49 evaluable patients). No patient lost a previously achieved response. There were no cases of de novo grade 3 or 4 graft-versus-host disease, graft failure, or infusion-related toxicities. BKV-CTLs were identified in patient blood samples up to 3 months postinfusion and their in vivo expansion predicted for clinical response. A matched-pair analysis revealed that, compared with standard of care, after accounting for prognostic covariate effects, treatment with BKV-CTLs resulted in higher probabilities of response at all follow-up timepoints as well as significantly lower transfusion requirement. CONCLUSION: Off-the-shelf BKV-CTLs are a safe and effective therapy for the management of patients with BKV-HC after AHSCT.


Assuntos
Cistite/tratamento farmacológico , Transtornos Hemorrágicos/tratamento farmacológico , Linfócitos T Citotóxicos/metabolismo , Alotransplante de Tecidos Compostos Vascularizados/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
5.
Oncoimmunology ; 10(1): 1877415, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33643693

RESUMO

Acute tubular interstitial nephritis (ATIN) is the most frequently reported pathology in patients with checkpoint inhibitor (CPI) induced acute kidney injury (AKI). Glucocorticoid (GC) therapy and discontinuation of CPI are the mainstay of treatment to prevent permanent renal dysfunction and dialysis. However, less than 50% of patients have complete kidney recovery and relapse of ATIN can occur. Infliximab is effective in treating other immune-related adverse events but its use for the treatment of CPI-ATIN is not well established. We report the first retrospective study examining the steroid-sparing potential of infliximab in achieving durable and complete renal recovery for patients with CPI-ATIN. Data were collected from medical records of patients diagnosed with CPI-AKI with a kidney biopsy or clinical diagnosis of ATIN that was managed with GC and infliximab. Infliximab-containing regimens were used to treat 10 patients with CPI-ATIN. Four patients relapsing after GC therapy achieved durable and complete renal recovery, four patients experienced partial renal recovery, and two patients showed no improvement in kidney function. This is the first study evaluating clinical outcomes using an infliximab-containing regimen for treatment of relapsed CPI-ATIN in patients or patients failing to achieve complete response after primary therapy. Our data suggest that infliximab may be a treatment option for achieving durable and complete renal recovery in this patient population and represents a potential steroid-sparing strategy in challenging cases of CPI-ATIN. Rigorous clinical studies are warranted to evaluate the risk-benefit analysis for infliximab usage in CPI-ATIN patients.


Assuntos
Nefrite Intersticial , Diálise Renal , Humanos , Infliximab/efeitos adversos , Rim , Nefrite Intersticial/induzido quimicamente , Estudos Retrospectivos
6.
J Immunother Cancer ; 9(2)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33637601

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) are being used after allogeneic hematopoietic stem cell transplantation (alloHCT) to reverse immune dysfunction. However, a major concern for the use of ICIs after alloHCT is the increased risk of graft-versus-host disease (GVHD). We analyzed the association between GVHD prophylaxis and frequency of GVHD in patients who had received ICI therapy after alloHCT. METHODS: A retrospective study was performed in 21 patients with acute myeloid leukemia (n=16) or myelodysplastic syndromes (n=5) who were treated with antiprogrammed cell death protein 1 (16 patients) or anticytotoxic T lymphocyte-associated antigen 4 (5 patients) therapy for disease relapse after alloHCT. Associations between the type of GVHD prophylaxis and incidence of GVHD were analyzed. RESULTS: Four patients (19%) developed acute GVHD. The incidence of acute GVHD was associated only with the type of post-transplantation GVHD prophylaxis; none of the other variables included (stem cell source, donor type, age at alloHCT, conditioning regimen and prior history of GVHD) were associated with the frequency of acute GVHD. Twelve patients received post-transplantation cyclophosphamide (PTCy) for GVHD prophylaxis. Patients who received PTCy had a significantly shorter median time to initiation of ICI therapy after alloHCT compared with patients who did not receive PTCy (median 5.1 months compared with 26.6 months). Despite early ICI therapy initiation, patients who received PTCy had a lower observed cumulative incidence of grades 2-4 acute GVHD compared with patients who did not receive PTCy (16% compared with 22%; p=0.7). After controlling for comorbidities and time from alloHCT to ICI therapy initiation, the analysis showed that PTCy was associated with a 90% reduced risk of acute GVHD (HR 0.1, 95% CI 0.02 to 0.6, p=0.01). CONCLUSIONS: ICI therapy for relapsed acute myeloid leukemia/myelodysplastic syndromes after alloHCT may be a safe and feasible option. PTCy appears to decrease the incidence of acute GVHD in this cohort of patients.

7.
Kidney Int ; 100(1): 196-205, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33359528

RESUMO

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.


Assuntos
Carcinoma de Células Escamosas , Transplante de Rim , Neoplasias Cutâneas , Carcinoma de Células Escamosas/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Transplante de Rim/efeitos adversos , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico
8.
Adv Exp Med Biol ; 1342: 389-397, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34972976

RESUMO

With the increasing use of immunotherapy, there has been an associated increased survival in many cancers but has also resulted in unregulated organ-specific toxicities. In this review, we will discuss the renal toxicities associated with a checkpoint inhibitor (CPI) from the typical acute tubulointerstitial nephritis to glomerulonephritis and their proposed mechanisms and treatments. We also discuss the use of CPI and reactivation of preexisting autoimmune disease with a focus on renal cell cancer in setting of chronic kidney disease (CKD). Transplant rejection in setting of CPI use has been further evaluated with single-center and multicenter retrospective studies, and available data will be presented in this chapter.


Assuntos
Neoplasias , Nefrite Intersticial , Insuficiência Renal Crônica , Humanos , Imunoterapia , Estudos Multicêntricos como Assunto , Estudos Retrospectivos
9.
J Immunother Cancer ; 8(2)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33020246

RESUMO

The same mechanisms that mediate antitumor immunity from checkpoint inhibitors (CPIs) can also lead to unintended targeting of normal tissues, characterized as immune-related adverse events (irAEs). Those with pre-existing autoimmune disease are believed to be particularly vulnerable for exacerbating underlying autoimmunity or inducing severe irAEs. We report the first case of CPI-associated reactivation of primary membranous nephropathy (MN) in a patient with pleural mesothelioma responding to immunotherapy. Due to its specificity in targeting B-lymphocytes, rituximab was used to treat primary MN with the expectation that this would not interfere with the benefits gained from T cell-mediated antitumor immunity. Rituximab was effective in treating CPI-associated reactivation of MN, and the patient was successfully rechallenged with nivolumab and maintained stable kidney function and sustained clinical antitumor effect. While exacerbation of pre-existing autoimmune diseases from CPIs is common, therapy for autoimmune reactivation can be rationally directed by an understanding of the immunosuppressive mechanism with goals of cancer treatment.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/métodos , Rituximab/uso terapêutico , Antineoplásicos Imunológicos/farmacologia , Glomerulonefrite Membranosa/induzido quimicamente , Glomerulonefrite Membranosa/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Rituximab/farmacologia
10.
J Immunother Cancer ; 8(2)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32718987

RESUMO

The percentage of patients with cancer eligible for checkpoint inhibitor (CPI) therapy has increased rapidly over the past few years and approaches 45%. As a result, more cases of CPI-related nephrotoxicity, including a rare subset with vasculitis, are being reported. To elucidate the clinical presentation of CPI-associated renal vasculitis and its possible mechanisms, treatment options and prognosis, we describe cases from a comprehensive cancer center and reviewed the literature for similar cases. We retrospectively reviewed the charts of all patients with cancer from 2014 to 2020 who were diagnosed with CPI-related nephrotoxicity and underwent a kidney biopsy. We identified five cases of renal vasculitis: three patients were diagnosed with seronegative antineutrophil cytoplasm antibody (ANCA)-associated vasculitis, one case with seropositive ANCA-associated vasculitis and one case was diagnosed with IgA vasculitis. Of these cases, four patients were receiving nivolumab, and one patient was receiving tremelimumab. All patients had microscopic hematuria, four out of five patients had negative ANCA serology, one patient had concurrent lung involvement and positive ANCA serology, and all had severe acute kidney injury with creatinine >4.50 mg/dL on diagnosis. All patients were treated by discontinuing CPI and initiating corticosteroids and rituximab. Three patients received plasmapheresis; two of these required renal replacement therapy including the patient with lung involvement. All patients after rituximab had a partial or complete renal response. Two patients died within 8 months of diagnosis due to malignancy progression. None of the patients had a relapse of vasculitis. We demonstrated that CPI can be associated with different types of renal vasculitis that are predominantly ANCA negative and manifest as severe acute kidney injury. Despite the lack of strong evidence, treatment similar to treatment of primary seropositive ANCA-associated vasculitis with corticosteroids and rituximab is well tolerated with favorable renal outcomes.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Antineoplásicos Imunológicos/uso terapêutico , Ativação Linfocitária/imunologia , Rituximab/uso terapêutico , Adulto , Idoso , Antineoplásicos Imunológicos/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab/farmacologia
11.
Leuk Lymphoma ; 61(13): 3101-3111, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32723196

RESUMO

The long-term impact of Autologous hematopietic stem cell transplantation (ASCT) on renal function, and the impact of renal function on progression-free survival (PFS) and overall survival (OS) in patients with multiple myeloma are not known. We retrospectively reviewed the records of 885 patients at our institution. We used linear mixed effect models to study the change in estimated glomerular filtration rate (eGFR) and a joint model approach to assess associations between the eGFR, PFS and OS. Sensitivity analyses were conducted at days 0, 100, 180, and 365 post-SCT. eGFR post-ASCT was significantly lower than at day 0 but stabilized at approximately 80 mL/min/1.73 m2. There was no association between eGFR and PFS or OS.; However, relapsed disease and ISS stage were associated with shorter PFS and OS. This data suggests that although there is a modest decline in eGFR post-ASCT, it is not associated with an adverse impact on PFS or OS. KEY POINTS Advanced MM stage at diagnosis was associated with reduced eGFR at all stages of chronic kidney disease. eGFR was not associated with PFS or OS in any of the analyses, but disease-related factors prior to ASCT were all associated with reduced eGFR, PFS and OS. ASCT did not adversely impact kidney function and mitigated the risk of CKD on outcomes in MM.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Intervalo Livre de Doença , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Transplante de Células-Tronco , Transplante Autólogo , Resultado do Tratamento
12.
Transpl Infect Dis ; 22(5): e13395, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32602954

RESUMO

BACKGROUND: BK polymavirus (BKPyV), a member of the family Polyomaviridae, is associated with increased morbidity and mortality in allogeneic stem cell transplant recipients. METHODS: In our previous retrospective study of 2477 stem cell transplant patients, BKPyV replication independently predicted chronic kidney disease and poor survival. In this study, using the same cohort, we derived and validated a risk grading system to identify patients at risk of BKPyV replication after transplantation in a user-friendly modality. We used 3 baseline variables (conditioning regimen, HLA match status, and underlying cancer diagnosis) that significantly predicted BKPyV replication in our initial study in a subdistribution hazard model with death as a competing risk. We also developed a nomogram of the hazard model as a visual aid. The AUC of the ROC of the risk-score-only model was 0.65. We further stratified the patients on the basis of risk score into low-, moderate-, and high-risk groups. RESULTS: The total risk score was significantly associated with BKPyV replication (P < .0001). At 30 days after transplantation, the low-risk (score ≤ 0) patients had a 9% chance of developing symptomatic BKPyV replication, while the high-risk (score ≥ 8) of the population had 56% of developing BKPyV replication. We validated the risk score using a separate cohort of 1478 patients. The AUC of the ROC of the risk-score-only model was 0.59. Both the total risk score and 3-level risk variable were significantly associated with BKPyV replication in this cohort (P < .0001). CONCLUSIONS: This grading system for the risk of symptomatic BKPyV replication may help in early monitoring and intervention to prevent BKPyV-associated morbidity, mortality, and kidney function decline.


Assuntos
Vírus BK , Transplante de Células-Tronco Hematopoéticas , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Estudos Retrospectivos , Medição de Risco , Transplante de Células-Tronco , Transplantados
13.
Eur J Cancer ; 132: 141-149, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32361629

RESUMO

A precise and efficient method for estimating kidney function in cancer patients is important to determine their eligibility for clinical trials and surgery and to allow for appropriate dose adjustment of anti-cancer drugs, especially toxic drugs with a narrow therapeutic index. Since direct measurement of glomerular filtration rate (GFR) is cumbersome, several formulae have been developed to estimate kidney function. Most of these are based on serum creatinine concentration. Though the CKD-EPI formula is recognised as being the most accurate, there is an ongoing debate on which is the optimal formula for cancer patients. In this review, we provide an overview of different GFR estimating equations for kidney function and the advantages and disadvantages of each method and compare their performance in cancer patients. We discuss the importance of body surface area-indexing and propose a framework for evaluating kidney function in cancer patients.


Assuntos
Antineoplásicos/efeitos adversos , Taxa de Filtração Glomerular , Testes de Função Renal , Neoplasias/tratamento farmacológico , Insuficiência Renal Crônica/patologia , Humanos , Neoplasias/patologia , Prognóstico , Insuficiência Renal Crônica/induzido quimicamente
14.
Adv Exp Med Biol ; 1244: 287-293, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32301023

RESUMO

With the increasing use of immunotherapy, there has been an associated increased survival in many cancers but has also resulted in unregulated organ-specific toxicities. In this chapter, we discuss the renal toxicities associated with a checkpoint inhibitor (CPI) from the typical acute tubulointersitial nephritis to glomerulonephritis, their proposed mechanisms, and treatments. We also discuss the use of CPI and reactivation of preexisting auto-immune diseases and focus on renal cell cancer in setting of Chronic kidney disease (CKD). Transplant rejection in the setting of CPI use is yet to be further studied, and available data is presented in this chapter.


Assuntos
Rejeição de Enxerto/induzido quimicamente , Imunoterapia/efeitos adversos , Neoplasias/terapia , Nefrite/induzido quimicamente , Rejeição de Enxerto/imunologia , Humanos , Neoplasias/complicações , Neoplasias/imunologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/cirurgia
15.
J Am Soc Nephrol ; 31(2): 435-446, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31896554

RESUMO

BACKGROUND: Despite increasing recognition of the importance of immune checkpoint inhibitor-associated AKI, data on this complication of immunotherapy are sparse. METHODS: We conducted a multicenter study of 138 patients with immune checkpoint inhibitor-associated AKI, defined as a ≥2-fold increase in serum creatinine or new dialysis requirement directly attributed to an immune checkpoint inhibitor. We also collected data on 276 control patients who received these drugs but did not develop AKI. RESULTS: Lower baseline eGFR, proton pump inhibitor use, and combination immune checkpoint inhibitor therapy were each independently associated with an increased risk of immune checkpoint inhibitor-associated AKI. Median (interquartile range) time from immune checkpoint inhibitor initiation to AKI was 14 (6-37) weeks. Most patients had subnephrotic proteinuria, and approximately half had pyuria. Extrarenal immune-related adverse events occurred in 43% of patients; 69% were concurrently receiving a potential tubulointerstitial nephritis-causing medication. Tubulointerstitial nephritis was the dominant lesion in 93% of the 60 patients biopsied. Most patients (86%) were treated with steroids. Complete, partial, or no kidney recovery occurred in 40%, 45%, and 15% of patients, respectively. Concomitant extrarenal immune-related adverse events were associated with worse renal prognosis, whereas concomitant tubulointerstitial nephritis-causing medications and treatment with steroids were each associated with improved renal prognosis. Failure to achieve kidney recovery after immune checkpoint inhibitor-associated AKI was independently associated with higher mortality. Immune checkpoint inhibitor rechallenge occurred in 22% of patients, of whom 23% developed recurrent associated AKI. CONCLUSIONS: This multicenter study identifies insights into the risk factors, clinical features, histopathologic findings, and renal and overall outcomes in patients with immune checkpoint inhibitor-associated AKI.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Antígeno B7-H1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , Idoso , Feminino , Humanos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/induzido quimicamente , Estudos Retrospectivos , Fatores de Risco
16.
Am J Hosp Palliat Care ; 37(9): 707-715, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31986903

RESUMO

INTRODUCTION: In patients with advanced cancer, prolongation of life with treatment often incurs substantial emotional and financial expense. Among hospitalized patients with cancer since acute kidney injury (AKI) is known to be associated with much higher odds for hospital mortality, we investigated whether renal replacement therapy (RRT) use in the intensive care unit (ICU) was a significant independent predictor of worse outcomes. METHODS: We retrospectively reviewed patients admitted in 2005 to 2014 who were diagnosed with stage IV solid tumors, had AKI, and a nephrology consult. The main outcomes were survival times from the landmark time points, inpatient mortality, and longer term survival after hospital discharge. Logistic regression and Cox proportional regression were used to compare inpatient mortality and longer term survival between RRT and non-RRT groups. Propensity score-matched landmark survival analyses were performed with 2 landmark time points chosen at day 2 and at day 7 from ICU admission. RESULTS: Of the 465 patients with stage IV cancer admitted to the ICU with AKI, 176 needed RRT. In the multivariate logistic regression model after adjusting for baseline serum albumin and baseline maximum Sequential Organ Failure Assessment (SOFA), the patients who received RRT were not significantly different from non-RRT patients in inpatient mortality (odds ratio: 1.004 [95% confidence interval: 0.598-1.684], P = .9892). In total, 189 patients were evaluated for the impact of RRT on long-term survival and concluded that RRT was not significantly associated with long-term survival after discharge for patients who discharged alive. Landmark analyses at day 2 and day 7 confirmed the same findings. CONCLUSIONS: Our study found that receiving RRT in the ICU was not significantly associated with inpatient mortality, survival times from the landmark time points, and long-term survival after discharge for patients with stage IV cancer with AKI.


Assuntos
Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/terapia , Neoplasias/epidemiologia , Terapia de Substituição Renal/estatística & dados numéricos , Injúria Renal Aguda/mortalidade , Idoso , Institutos de Câncer/estatística & dados numéricos , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/mortalidade , Neoplasias/patologia , Escores de Disfunção Orgânica , Estudos Retrospectivos , Análise de Sobrevida
17.
J Immunother Cancer ; 7(1): 158, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234936

RESUMO

Following publication of the original article [1], the authors reported an error in the Acknowledgments section. It should be read: 'We are grateful to Mohsin Shah from the Department of Emergency Medicine at The University of Texas MD Anderson Cancer Center for assisting in study selection, and to Gregory F. Pratt from the Research Medical Library and Erica Goodoff, from the Department of Scientific Publications at The University of Texas MD Anderson Cancer Center for their valuable contributions.

18.
Ann Hematol ; 98(7): 1611-1616, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31093708

RESUMO

Recent evidence suggests that renal dysfunction may be a direct consequence of primary myelofibrosis (PMF). We performed a retrospective analysis of 100 patients with previously untreated PMF, receiving frontline treatment with single agent ruxolitinib, and compared them to 105 patients, receiving frontline treatment with a non-ruxolitinib-based therapy, matched by age, sex, DIPSS plus, and estimated glomerular filtration rate (eGFR). Use of ruxolitinib associated with a significantly higher rate of renal improvement (RI) > 10% (73% vs 50%, p = 0.01) confirmed on multivariate analysis (MVA) [odds ratio 3, 95% confidence interval (CI) 1.6-5.5, p < 0.001]. After a median follow-up of 41 months (range, 1-159 months), median failure-free survival (FFS) was 14 months (range, 1-117 months). Achievement of a RI > 10% maintained its independent association with prolonged FFS on MVA (hazard ratio 1.4, 95% CI 1.1-2, p = 0.02). Ruxolitinib can significantly improve renal function in patients with PMF, significantly impacting failure-free survival.


Assuntos
Bases de Dados Factuais , Taxa de Filtração Glomerular/efeitos dos fármacos , Rim , Mielofibrose Primária , Pirazóis/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Rim/metabolismo , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nitrilas , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/metabolismo , Mielofibrose Primária/mortalidade , Mielofibrose Primária/fisiopatologia , Pirimidinas , Estudos Retrospectivos , Taxa de Sobrevida
19.
J Immunother Cancer ; 7(1): 106, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30992053

RESUMO

BACKGROUND: Checkpoint inhibitors (CPIs) have revolutionized the treatment of cancer, but their use remains limited by off-target inflammatory and immune-related adverse events. Solid organ transplantation (SOT) recipients have been excluded from clinical trials owing to concerns about alloimmunity, organ rejection, and immunosuppressive therapy. Thus, we conducted a retrospective study and literature review to evaluate the safety of CPIs in patients with cancer and prior SOT. METHODS: Data were collected from the medical records of patients with cancer and prior SOT who received CPIs at The University of Texas MD Anderson Cancer Center from January 1, 2004, through March 31, 2018. Additionally, we systematically reviewed five databases through April 2018 to identify studies reporting CPIs to treat cancer in SOT recipients. We evaluated the safety of CPIs in terms of alloimmunity, immune-related adverse events, and mortality. We also evaluated tumor response to CPIs. RESULTS: Thirty-nine patients with allograft transplantation were identified. The median age was 63 years (range 14-79 years), 74% were male, 62% had metastatic melanoma, 77% received anti-PD-1 agents, and 59% had prior renal transplantation, 28% hepatic transplantation, and 13% cardiac transplantation. Median time to CPI initiation after SOT was 9 years (range 0.92-32 years). Allograft rejection occurred in 41% of patients (11/23 renal, 4/11 hepatic, and 1/5 cardiac transplantations), at similar rates for anti-CTLA-4 and anti-PD-1 therapy. The median time to rejection was 21 days (95% confidence interval 19.3-22.8 days). There were no associations between time since SOT and frequency, timing, or type of rejection. Overall, 31% of patients permanently discontinued CPIs because of allograft rejection. Graft loss occurred in 81%, and death was reported in 46%. Of the 12 patients with transplantation biopsies, nine (75%) had acute rejection, and five of these rejections were T cell-mediated. In melanoma patients, 36% responded to CPIs. CONCLUSIONS: SOT recipients had a high allograft rejection rate that was observed shortly after CPI initiation, with high mortality rates. Further studies are needed to optimize the anticancer treatment approach in these patients.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Rejeição de Enxerto/epidemiologia , Neoplasias/tratamento farmacológico , Transplante de Órgãos/efeitos adversos , Adolescente , Adulto , Idoso , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Feminino , Seguimentos , Rejeição de Enxerto/induzido quimicamente , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/imunologia , Neoplasias/mortalidade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Estudos Retrospectivos , Medição de Risco , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Adulto Jovem
20.
J Immunother Cancer ; 7(1): 2, 2019 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-30612580

RESUMO

RATIONALE & OBJECTIVE: The approved therapeutic indication for immune checkpoint inhibitors (CPIs) are rapidly expanding including treatment in the adjuvant setting, the immune related toxicities associated with CPI can limit the efficacy of these agents. The literature on the nephrotoxicity of CPI is limited. Here, we present cases of biopsy proven acute tubulointerstitial nephritis (ATIN) and glomerulonephritis (GN) induced by CPIs and discuss potential mechanisms of these adverse effects. STUDY DESIGN, SETTING, & PARTICIPANTS: We retrospectively reviewed all cancer patients from 2008 to 2018 who were treated with a CPI and subsequently underwent a kidney biopsy at The University of Texas MD Anderson Cancer Center. RESULTS: We identified 16 cases diagnosed with advanced solid or hematologic malignancy; 12 patients were male, and the median age was 64 (range 38 to 77 years). The median time to developing acute kidney injury (AKI) from starting CPIs was 14 weeks (range 6-56 weeks). The average time from AKI diagnosis to obtaining renal biopsy was 16 days (range from 1 to 46 days). Fifteen cases occurred post anti-PD-1based therapy. ATIN was the most common pathologic finding on biopsy (14 of 16) and presented in almost all cases as either the major microscopic finding or as a mild form of interstitial inflammation in association with other glomerular pathologies (pauci-immune glomerulonephritis, membranous glomerulonephritis, C3 glomerulonephritis, immunoglobulin A (IgA) nephropathy, or amyloid A (AA) amyloidosis). CPIs were discontinued in 15 out of 16 cases. Steroids and further immunosuppression were used in most cases as indicated for treatment of ATIN and glomerulonephritis (14 of 16), with the majority achieving complete to partial renal recovery. CONCLUSIONS: Our data demonstrate that CPI related AKI occurs relatively late after CPI therapy. Our biopsy data demonstrate that ATIN is the most common pathological finding; however it can frequently co-occur with other glomerular pathologies, which may require immune suppressive therapy beyond corticosteroids. In the lack of predictive blood or urine biomarker, we recommend obtaining kidney biopsy for CPI related AKI.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Imunomodulação/efeitos dos fármacos , Terapia de Alvo Molecular/efeitos adversos , Neoplasias/complicações , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/etiologia , Adulto , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Biópsia , Feminino , Glomerulonefrite/diagnóstico , Glomerulonefrite/etiologia , Glomerulonefrite/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Nefrite Intersticial/metabolismo , Nefrite Intersticial/terapia , Prognóstico
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