Checkpoint inhibition in immunosuppressed or immunocompromised patients with advanced cutaneous squamous cell carcinoma (CSCC): Data from prospective CemiplimAb-rwlc Survivorship and Epidemiology (C.A.S.E.) study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9547-9547
Author(s):  
Guilherme Rabinowits ◽  
Soo J Park ◽  
David M. Ellison ◽  
Francis P. Worden ◽  
Rhonda W. Gentry ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Hematologic Malignancy ◽  
Objective Response ◽  
Organ Transplant ◽  
Immunosuppressed Patient ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Increased Risk ◽  
Initial Cohort

9547 Background: Immunosuppressed and/or immunocompromised patients are at increased risk for solid tumors and cutaneous malignancies. Limited data exist on the safety and effectiveness of immune checkpoint inhibitors (ICIs) in these patients because they are frequently excluded from clinical trials. Here, we describe the safety and effectiveness results from the initial cohort of immunosuppressed and/or immunocompromised patients with advanced CSCC enrolled in the C.A.S.E. study (NCT03836105). Methods: C.A.S.E. is a prospective, real-world, multi-center, longitudinal study evaluating the effectiveness, safety, quality of life, and survivorship in patients with advanced CSCC treated with cemiplimab. Patients received cemiplimab 350 mg intravenously every 3 weeks per routine standard of care. Patient demographics, disease characteristics, immunosuppression, and relevant medical history were collected. Immunosuppressive regimens varied amongst patients. Investigator assessment of objective response rate (ORR), safety, and tolerability was conducted. Data from 26 immunosuppressed and/or immunocompromised patients with advanced CSCC treated with cemiplimab are presented. Recruitment is ongoing. Results: As of November 17, 2020, 121 patients were enrolled in the C.A.S.E. study, of which 26 patients (median age: 74 years [IQR: 71-84]; 85% male; 89% Caucasian) were designated as immunocompromised or immunosuppressed due to a history of solid organ transplant (n = 6), autoimmune disorder (n = 11), or hematologic malignancy (n = 9). Median duration of cemiplimab exposure was 14 months (IQR: 9.1–42, range: 0, 67). Among 19 immunocompromised or immunosuppressed patients who enrolled in C.A.S.E. prior to their third dose of cemiplimab, ORR per investigator assessment was 47% (95% CI: 24–71); 1 (5%) patient had complete response; 8 (42%) had partial response. One patient had a treatment-related serious adverse reaction of organ transplant rejection. One (3.8%) patient discontinued treatment due to increased alanine aminotransferase (not treatment-related). Immune-related AEs (irAEs) occurred in 23% of patients. No treatment-related AEs led to death. Conclusions: The safety, tolerability, and effectiveness of cemiplimab in this initial cohort of immunosuppressed and/or immunocompromised patients with advanced CSCC appear to be consistent with those observed in clinical trials that excluded these patients. Further follow-up and additional data would add to our general understanding of safety and effectiveness of anti-PD1 therapy in immunocompromised and/or immunosuppressed patient populations overall. Clinical trial information: NCT03836105.

scholarly journals Gastric Mucormycosis: An Infection of Fungal Invasion into the Gastric Mucosa in Immunocompromised Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Haider A. Naqvi ◽  
Muhammad Nadeem Yousaf ◽  
Fizah S. Chaudhary ◽  
Lawrence Mills
Keyword(s):  
Abdominal Pain ◽  
Gastric Mucosa ◽  
Chronic Renal Disease ◽  
Hematologic Malignancy ◽  
Acute Onset ◽  
The Body ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Presenting Symptoms ◽  
Increased Risk

Primary gastric mucormycosis is a rare but potentially lethal fungal infection due to the invasion of Mucorales into the gastric mucosa. It may result in high mortality due to increased risk of complications in immunocompromised patients. Common predisposing risk factors to develop gastric mucormycosis are prolonged uncontrolled diabetes mellitus with or without diabetic ketoacidosis (DKA), solid organ or stem cell transplantation, underlying hematologic malignancy, and major trauma. Abdominal pain, hematemesis, and melena are common presenting symptoms. The diagnosis of gastric mucormycosis can be overlooked due to the rarity of the disease. A high index of suspicion is required for early diagnosis and management of the disease, particularly in immunocompromised patients. Radiological imaging findings are nonspecific to establish the diagnosis, and gastric biopsy is essential for histological confirmation of mucormycosis. Prompt treatment with antifungal therapy is the mainstay of treatment with surgical resection reserved in cases of extensive disease burden or clinical deterioration. We presented a case of acute gastric mucormycosis involving the body of stomach in a patient with poorly controlled diabetes and chronic renal disease, admitted with acute onset of abdominal pain. Complete resolution of lesion was noted with 16 weeks of medical treatment with intravenous amphotericin B and posaconazole.

Human Papillomavirus, Herpes Zoster, and Hepatitis B Vaccinations in Immunocompromised Patients: An Update for Pharmacists

2020 ◽  
pp. 089719002095826
Author(s):  
Michelle R. Paulsen ◽  
Nikitha R. Patel ◽  
Carol Sulis ◽  
Francis A. Farraye ◽  
Shubha Bhat
Keyword(s):  
Human Papillomavirus ◽  
Herpes Zoster ◽  
Hepatitis B ◽  
Organ Transplant ◽  
Current Evidence ◽  
Solid Organ ◽  
Cell Transplant ◽  
Immunocompromised Patients ◽  
Hematopoietic Stem ◽  
Increased Risk

Purpose: Current evidence regarding efficacy and safety of human papillomavirus 9-valent (9vHPV), recombinant zoster (RZV), and CpG-adjuvanted recombinant hepatitis B (HepB-CpG) vaccines in adults with human immunodeficiency virus, inflammatory bowel disease, solid organ transplant, and allogeneic hematopoietic stem cell transplant is reviewed. Summary: Patients immunocompromised due to underlying disease or treatment are at increased risk for infections; however, insufficient understanding of various vaccines’ efficacy, safety, indications, and contraindications in this population has led to suboptimal vaccination rates. The Infectious Disease Society of America (IDSA) published guidelines on vaccines in immunocompromised populations in 2013. Since then, several advances have been made including an expanded indication with 9vHPV for use in males and females 9 to 45 years old, and the introduction of new vaccines for herpes zoster (RZV) and hepatitis B (HepB-CpG). Pharmacists are instrumental to vaccination efforts and may benefit from a review of recent vaccine updates. Conclusion: The 9vHPV can be used in men and women ages 9 to 45 years old regardless of immune status. RZV safety and efficacy in several immunocompromised populations has been demonstrated; however, manufacturers and major societies have yet to update their recommendations. HepB-CpG may be used in most immunocompromised patients yet remains under-utilized.

scholarly journals Clinical Characteristics and Radiologic Features of Immunocompromised Patients With Pauci-Bacillary Pulmonary Tuberculosis Receiving Delayed Diagnosis and Treatment

2019 ◽  
Vol 6 (2) ◽  
Author(s):  
Joung Ha Park ◽  
Jooae Choe ◽  
Moonsuk Bae ◽  
Sungim Choi ◽  
Kyung Hwa Jung ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Hematologic Malignancy ◽  
Diagnostic Delay ◽  
Organ Transplant ◽  
Delayed Diagnosis ◽  
Tertiary Hospital ◽  
The Other ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Radiologic Features

Abstract Background Pauci-bacillary pulmonary tuberculosis (TB) can be delayed to diagnose and start anti-TB therapy, especially in immunocompromised patients. We therefore evaluated the clinical and radiologic features of these delayed cases. Methods Immunocompromised adult patients with pauci-bacillary pulmonary TB were retrospectively enrolled in a tertiary hospital in an intermediate–TB burden country over a 5-year period. We defined “missed TB” or “not-missed TB” patients as those who started anti-TB therapy after or before positive mycobacterial culture results, respectively. Results Of 258 patients, 134 (52%) were classified in the missed TB group, and 124 (48%) in the not-missed TB group. Positive results of molecular tests including MTB polymerase chain reaction and/or Xpert TB/RIF were only obtained in the not-missed TB group (54/106, 54%). The median diagnostic delay in the missed TB group was longer than in the other group (30 vs 6 days; P < .001). In the missed TB group, the most common working diagnoses were pneumonia (46, 34%) and lung metastasis of malignancy (40, 30%). Typical radiologic findings for TB, such as upper lobe predominance and centrilobular nodules with tree-in-bud appearance, were less common in the missed TB group than in the other group. Old age (odds ratio [OR], 1.03), solid organ transplant (OR, 3.46), solid tumor (OR, 3.83), and hematologic malignancy (OR, 4.04) were independently associated with missed TB. Conclusions Care is needed to differentiate pauci-bacillary TB, especially in immunocompromised patients with the mentioned risk factors, even without the usual radiologic features of TB. Additional rapid diagnostic tests to rule out pauci-bacillary TB are urgently needed.

scholarly journals Effects of Monoclonal Gammopathy of Undetermined Significance (MGUS) on Outcomes after Solid Organ Transplant

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3507-3507
Author(s):  
Teresa E Goebel ◽  
Nicholas K Schiltz ◽  
Aiswarya Chandran Pillai ◽  
Paolo Caimi ◽  
Siran M Koroukian ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Hematologic Malignancy ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Lymphoproliferative Disease ◽  
Solid Organ ◽  
Transplant Patients ◽  
Diagnosis Codes ◽  
Increased Risk ◽  
Increase Risk

Abstract Background: MGUS is a precancerous condition which can progress to multiple myeloma (MM) or other hematologic malignancy. MGUS increases the risk of developing MM approximately 25-fold, and increases lifetime risk of infection, venous thromboembolism (VTE), and skeletal related events (SRE). Solid organ transplant requires immunosuppression, which is associated with overlapping risks, including hematologic malignancy such as post transplant lymphoproliferative disease (PTLD). Hypothesizing that MGUS would further increase risk of PTLD and other complications after transplant, we described risk of these outcomes in patients with MGUS prior to solid organ transplant (MGUS+) compared to those without MGUS (MGUS-). Methods: We used the 2005-2011 California State Inpatient, Emergency, and Ambulatory Databases. MGUS and complications were identified by ICD-9 diagnosis codes, and solid organ transplant by ICD-9 procedure codes. Patients with the ICD-9 diagnosis code 273.1 documented on or before the day of solid organ transplant surgery were defined as MGUS+. We used logistic regression to analyze complications in MGUS+ versus MGUS- transplant patients. Results: Of 24,358,669 patients, we identified 22,062 solid organ transplant patients. Transplant patients were 8.8% African American, 29.5% Hispanic, 43.4% White, 15.1% other, and 3.2% had data missing. 72 were MGUS+ prior to solid organ transplant. Median age of MGUS+ was 61.5 years versus 51 years for MGUS-. Outcomes are shown in table 1. Table 1. Transplant Patients Outcome MGUS + N=72 MGUS – N=21,990 Odds Ratio (95% CI) PTLD 0 161 n/a MM ≤10 37 34.90 (12.11, 100.61) Lymphoma 0 193 n/a VTE 20 3,202 2.26(1.35, 3.79) SRE 18 2,320 2.83(1.66, 4.83) Infection 50 11,612 2.03(1.23, 3.36) *Frequencies ≤10 are reported as such per the data use agreement. Conclusions: Compared to MGUS-, MGUS+ solid organ transplant patients had higher risk of VTE, SRE, and infection, but did not have higher risk of PTLD or other lymphomas. MGUS+ transplant patients are more likely to develop MM than MGUS-; however, this risk is similar to that historically attributed to MGUS, in patients who have not undergone transplant. These data show increased risk of certain complications in MGUS+ patients, and do not support screening for MGUS to assess risk of PTLD prior to solid organ transplant. Disclosures No relevant conflicts of interest to declare.

scholarly journals Angiogenesis Inhibitors as Anti-Cancer Therapy Following Renal Transplantation: A Case Report and Review of the Literature

2021 ◽  
Vol 28 (1) ◽  
pp. 661-670
Author(s):  
Lawrence Kasherman ◽  
Jeffrey Doi ◽  
Katherine Karakasis ◽  
Jeffrey Schiff ◽  
Abhijat Kitchlu ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Organ Transplant ◽  
Angiogenesis Inhibitors ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Immunosuppressive Medication ◽  
Increased Risk ◽  
Anti Cancer ◽  
Solid Organ Transplant Recipients

Solid organ transplant recipients on long-term immunosuppressive medication are at increased risk of developing malignancy, and treatment of advanced cancers with angiogenesis inhibitors in this context has not been widely studied. We present a case of recurrent high-grade serous ovarian carcinoma treated with paclitaxel and bevacizumab in the context of prior renal transplantation where the patient responded well to treatment with controlled toxicities, discussing the potential for increased rates of adverse events and drug interactions in this select population.

scholarly journals Risk of infection associated with targeted therapies for solid organ and hematological malignancies

2021 ◽  
Vol 8 ◽  
pp. 204993612198954
Author(s):  
Isabel Ruiz-Camps ◽  
Juan Aguilar-Company
Keyword(s):  
Hematological Malignancies ◽  
Opportunistic Infections ◽  
Respiratory Infections ◽  
Fungal Infections ◽  
Checkpoint Inhibitors ◽  
Janus Kinase ◽  
Prolonged Treatment ◽  
Solid Organ ◽  
Risk Of Infection ◽  
Increased Risk

Higher risks of infection are associated with some targeted drugs used to treat solid organ and hematological malignancies, and an individual patient’s risk of infection is strongly influenced by underlying diseases and concomitant or prior treatments. This review focuses on risk levels and specific suggestions for management, analyzing groups of agents associated with a significant effect on the risk of infection. Due to limited clinical experience and ongoing advances in these therapies, recommendations may be revised in the near future. Bruton tyrosine kinase (BTK) inhibitors are associated with a higher rate of infections, including invasive fungal infection, especially in the first months of treatment and in patients with advanced, pretreated disease. Phosphatidylinositol 3-kinase (PI3K) inhibitors are associated with an increased risk of Pneumocystis pneumonia and cytomegalovirus (CMV) reactivation. Venetoclax is associated with cytopenias, respiratory infections, and fever and neutropenia. Janus kinase (JAK) inhibitors may predispose patients to opportunistic and fungal infections; need for prophylaxis should be assessed on an individual basis. Mammalian target of rapamycin (mTOR) inhibitors have been linked to a higher risk of general and opportunistic infections. Breakpoint cluster region-Abelson (BCR-ABL) inhibitors are associated with neutropenia, especially over the first months of treatment. Anti-CD20 agents may cause defects in the adaptative immune response, hypogammaglobulinemia, neutropenia, and hepatitis B reactivation. Alemtuzumab is associated with profound and long-lasting immunosuppression; screening is recommended for latent infections and prevention strategies against CMV, herpesvirus, and Pneumocystis infections. Checkpoint inhibitors (CIs) may cause immune-related adverse events for which prolonged treatment with corticosteroids is needed: prophylaxis against Pneumocystis is recommended.

scholarly journals 735. Trends and Cost Analysis of Aspergillus Galactomannan testing at a Tertiary Medical Center

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S417-S417
Author(s):  
Peyton R Treutel ◽  
Anna Carr ◽  
Pradeep Bathina
Keyword(s):  
Stem Cell ◽  
Hematologic Malignancy ◽  
Medical Center ◽  
Organ Transplant ◽  
The Self ◽  
Solid Organ ◽  
Data Set ◽  
Hematopoietic Stem ◽  
Patients Âgés ◽  
Optical Density Index

Abstract Background Aspergillus is a fungus spread by inhalation of spores that can lead to invasive (IA), chronic, or allergic aspergillosis. Risk factors for IA include neutropenia, hematological malignancy, allogenic stem cell (HSCT) or solid organ transplant, severe immunodeficiency, or prolonged steroid use. An alternative to invasive tissue sampling, the serum Galactomannan (AGM) test detects a polysaccharide cell wall component of Aspergillus and can be used to determine a probable diagnosis of IA. Accuracy of AGM is related to disease burden and thus has the highest sensitivity and specificity in patients with hematologic malignancy or Hematopoietic stem cell transplantation (HSCT) at 70-82% and 86-92%, respectively. Studies have shown sensitivity to decline in other populations, with solid organ transplants as low as 20%. Methods We performed a retrospective study of all patients who received the AGM test at UMMC from January 3, 2013 to December 31, 2019. Patient Cohort Explorer was used to obtain de-identified patient data from EPIC. We obtained the number of encounters and patients on whom the AGM test was performed along with other variables. Billing offices provided the self-pay cost per AGM test. Results A total of 6,404 AGM tests were performed on 2,126 patients during 4,315 encounters in the study period. With a total of 499, 574, 984, 1140, 851, 1175 and 1181 tests done respectively from 2013 to 2019, a increasing trend was noted. The patients ages ranged from 1 to 89 with a median age of 52 years. A total of 3,055 tests were ordered in females, and 3,349 were ordered in males. At a cut off value (optical density index) of > 0.5, 183 AGM tests resulted positive in 108 patients and at a cut of > 1.0, 113 tests are positive in 70 patients. The rate of a positive AGM tests at > 0.5 was at 2.85% and at > 1.0 was at 1.76% over the study period. With the self-pay cost of each test at $134.54 in 2019 USD, the total cost of 6,404 tests was $861,594.16. Conclusion To our knowledge this data set constitutes the largest sample size of AGM testing. From our data, it seems that the rate of ordering this test has increased yearly. Relatively low percentage of these tests are positive, suggesting that it is most likely a large amount of these tests could have been ordered inappropriately or in the wrong clinical context. Disclosures All Authors: No reported disclosures

scholarly journals Exploring the Epidemiology of Cancer after Solid Organ Transplantation (EpCOT): an observational cohort study

BMJ Open ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. e043731
Author(s):  
Adnan Sharif ◽  
Javeria Peracha ◽  
David Winter ◽  
Raoul Reulen ◽  
Mike Hawkins
Keyword(s):  
Organ Transplantation ◽  
Record Linkage ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Study Cohort ◽  
Solid Organ ◽  
Post Transplantation ◽  
Increased Risk ◽  
Risk Of Cancer

IntroductionSolid organ transplant patients are counselled regarding increased risk of cancer (principally due to their need for lifelong immunosuppression) and it ranks as one of their biggest self-reported worries. Post-transplantation cancer is common, associated with increased healthcare costs and emerging as a leading cause of post-transplant mortality. However, epidemiology of cancer post-transplantation remains poorly understood, with limitations including translating data from different countries and national data being siloed across different registries and/or data warehouses.Methods and analysisStudy methodology for Epidemiology of Cancer after Solid Organ Transplantation involves record linkage between the UK Transplant Registry (from NHS Blood and Transplant), Hospital Episode Statistics (for secondary care episodes from NHS Digital), National Cancer Registry (from cancer registration data hosted by Public Health England) and the National Death Registry (from NHS Digital). Deterministic record linkage will be conducted by NHS Digital, with a fully anonymised linked dataset available for analysis by the research team. The study cohort will consist of up to 85 410 solid organ transplant recipients,who underwent a solid organ transplant in England between 1 January 1985 and 31 December 2015, with up-to-date outcome data.Ethics and disseminationThis study has been approved by the Confidentiality Advisory Group (reference: 16/CAG/0121), Research Ethics Committee (reference: 15/YH/0320) and Institutional Review Board (reference: RRK5471). The results of this study will be presented at national and international conferences, and manuscripts with results will be submitted for publication in high-impact peer-reviewed journals. The information produced will also be used to develop national evidence-based clinical guidelines to inform risk stratification to enable risk-based clinical follow-up.Trial registration numberNCT02991105.

scholarly journals Hepatitis E Virus Quasispecies and the Outcome of Acute Hepatitis E in Solid-Organ Transplant Patients

2012 ◽  
Vol 86 (18) ◽  
pp. 10006-10014 ◽  
Author(s):  
Sebastien Lhomme ◽  
Florence Abravanel ◽  
Martine Dubois ◽  
Karine Sandres-Saune ◽  
Lionel Rostaing ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Acute Hepatitis ◽  
Hepatitis E Virus ◽  
Organ Transplant ◽  
Hepatitis E ◽  
Solid Organ Transplant ◽  
First Year ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Serum Concentrations

Hepatitis E virus (HEV) infections are responsible for chronic hepatitis in immunocompromised patients, and this can evolve to cirrhosis. Like all RNA viruses, HEV exists as a mixture of heterogeneous viruses defining quasispecies. The relationship between the genetic heterogeneity described as a quasispecies, cytokine secretion, and the outcome of acute hepatitis in immunocompromised patients remains to be elucidated. We cloned and sequenced the region encoding the M and P capsid domains of HEV from eight solid-organ transplant (SOT) patients with acute HEV infection who subsequently cleared the virus and from eight SOT patients whose infection became chronic. We analyzed the cytokines and chemokines in the sera of these SOT patients by multianalyte profiling. The nucleotide sequence entropy and genetic distances were greater in patients whose infections became chronic. A lowerKa/Ksratio was associated with the persistence of HEV. The patients who developed chronic infection had lower serum concentrations of interleukin-1 (IL-1) receptor antagonist and soluble IL-2 receptor. Increased concentrations of the chemokines implicated in leukocyte recruitment to the liver were associated with persistent infection. Those patients with chronic HEV infection and progressing liver fibrosis had less quasispecies diversification during the first year than patients without liver fibrosis progression. Great quasispecies heterogeneity, a weak inflammatory response, and high serum concentrations of the chemokines involved in leukocyte recruitment to the liver in the acute phase were associated with persistent HEV infection. Slow quasispecies diversification during the first year was associated with rapidly developing liver fibrosis.

scholarly journals Hepatitis E Virus Immunopathogenesis

Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1180
Author(s):  
Kush Kumar Yadav ◽  
Scott P. Kenney
Keyword(s):  
Hepatitis E Virus ◽  
Organ Transplant ◽  
Hepatitis E ◽  
Oral Route ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
In Vivo Models ◽  
Transplant Patients

Hepatitis E virus is an important emerging pathogen producing a lethal impact on the pregnant population and immunocompromised patients. Starting in 1983, it has been described as the cause for acute hepatitis transmitted via the fecal–oral route. However, zoonotic and blood transfusion transmission of HEV have been reported in the past few decades, leading to the detailed research of HEV pathogenesis. The reason behind HEV being highly virulent to the pregnant population particularly during the third trimester, leading to maternal and fetal death, remains unknown. Various host factors (immunological, nutritional, hormonal) and viral factors have been studied to define the key determinants assisting HEV to be virulent in pregnant and immunocompromised patients. Similarly, chronic hepatitis is seen particularly in solid organ transplant patients, resulting in fatal conditions. This review describes recent advances in the immunopathophysiology of HEV infections in general, pregnant, and immunocompromised populations, and further elucidates the in vitro and in vivo models utilized to understand HEV pathogenesis.

Sign in / Sign up

Export Citation Format

Share Document