Infections in patients receiving immune checkpoint inhibitors.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 155-155
Author(s):  
Sutthichai Sae-Tia ◽  
Jarushka Naidoo ◽  
Seema Mehta
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Viral Infections ◽  
De Novo ◽  
Checkpoint Inhibitors ◽  
Laboratory Data ◽  
Hematologic Malignancies ◽  
Systemic Corticosteroids ◽  
Improved Outcomes ◽  
Infectious Diseases Consultation

155 Background: Immune checkpoint inhibitors (ICIs) - anti-PD-1 (nivolumab, pembrolizumab), anti-PD-L1 (atezolizumab, avelumab), anti-CTLA-4 (ipilimumab) - have improved outcomes for several malignancies. ICIs may cause immune-related adverse events (irAEs), often treated with immunosuppression. The incidence of infections arising de novo during ICI therapy or from immunosuppression for irAEs is not well described. Methods: In- and outpatients receiving ICIs were referred for Infectious Diseases consultation between 6/2011-6/2018. Twenty-five were randomly selected for retrospective summarization of the spectrum of infections. Diagnosis of infection was made by the primary oncologist, based upon clinical/radiographic/laboratory data. Results: Solid tumor (24, 96%) and hematologic malignancies (1, 4%) were represented (Table). All 25 had infections. 15 (60%) were male; median age 58 years (29-97). 17 (68%) had irAEs: pneumonitis (10, 40%), thyroiditis (5, 20%), colitis (5, 20%), hepatitis (4, 16%), dermatitis (4, 16%) and myocarditis (1, 4%). 17 (68%) patients developed +1 irAE. 50% with pneumonitis were concurrently treated for pneumonia. Of the 25, 17 (72%) developed de novo infections on ICIs; whereas others were receiving systemic corticosteroids (7, 28%) or infliximab (1, 4%). Initial infections included pneumonia (13, 52%), bacteremia (3, 12%), sinusitis (2, 8%), wound infection (2, 8%), viral infections (HSV, CMV, HCV; 1, 4% each) and 1 (4%) each of empyema, UTI, peritonitis, osteomyelitis, and meningitis. 44% (11) developed a second infection within 60 days of the first. Conclusions: Patients receiving ICIs for cancer developed a myriad of infections, both de novo during ICI therapy, or consequent to immunosuppression for irAEs. Second infections are common, occurring in nearly half the patients. Awareness of this is vital for early diagnosis and appropriate management. Patients with suspected ICI-related infection. (n=25). [Table: see text]

scholarly journals Immune-related adverse events of immune checkpoint inhibitors: a brief review

2018 ◽  
Vol 25 (5) ◽  
Author(s):  
G. Myers
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Health Care Professionals ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Hematologic Malignancies ◽  
T Cell Response ◽  
Proactive Management ◽  
Organ Systems

Immune checkpoint inhibitors (icis) such as inhibitors of ctla-4, PD-1, and PD-L1, given as monotherapy or combination therapy have emerged as effective treatment options for immune-sensitive solid tumours and hematologic malignancies. The benefits of icis can be offset by immune-related adverse events (iraes) that leave all organ systems vulnerable and subsequently increase the risk for morbidity and mortality.Because of fluctuating onset and prolonged duration, the toxicities associated with iraes represent a shift from the understanding of conventional anticancer toxicities. The ctla-4 and PD-1/PD-L1 inhibitors modulate T-cell response differently, resulting in distinct toxicity patterns, toxicity kinetics, and dose–toxicity relationships. Using individualized patient education, screening, and assessment for the early identification of iraes is key to proactive management and is therefore key to improving outcomes and prolonging therapy.Management of iraes is guided by appropriate grading, which sets the stage for the treatment setting (outpatient vs. inpatient), ici treatment course (delay vs. discontinuation), supportive care, corticosteroid use, organ specialist consultation, and additional immunosuppression. Health care professionals in oncology must work collaboratively with emergency and community colleagues to facilitate an understanding of iraes in an effort to optimize seamless care.

scholarly journals Overcoming Resistance to Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinomas

2021 ◽  
Vol 11 ◽  
Author(s):  
Lucas V. dos Santos ◽  
Carina M. Abrahão ◽  
William N. William
Keyword(s):  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
De Novo ◽  
Checkpoint Inhibitors ◽  
Acquired Resistance ◽  
Clinical Work ◽  
Squamous Cell Carcinomas ◽  
Clinical Activity

Preclinical data suggest that head and neck squamous cell carcinomas (HNSCC) may evade immune surveillance and induce immunosuppression. One mechanism of immune evasion involves the expression of programmed death ligand-1 (PD-L1) in tumor and immune cells, which is, to date, the only biomarker routinely used in clinical practice to select patients with advanced HNSCCs more likely to benefit from anti-PD-1 therapy. Nonetheless, PD-L1 expression alone incompletely captures the degree of sensitivity of HNSCCs to PD-1 inhibitors. Most patients exposed to anti-PD-1 antibodies do not respond to therapy, suggesting the existence of mechanisms of de novo resistance to immunotherapy. Furthermore, patients that initially respond to PD-1 inhibitors will eventually develop acquired resistance to immunotherapy through mechanisms that have not yet been completely elucidated. In this article, we will provide an overview of the immune landscape of HNSCCs. We will briefly describe the clinical activity of inhibitors of the PD-1/PD-L1 axis in this disease, as well as biomarkers of benefit from these agents that have been identified so far. We will review pre-clinical and clinical work in cancers in general, and in HNSCCs specifically, that have characterized the mechanisms of de novo and acquired resistance to immunotherapy. Lastly, we will provide insights into novel strategies under investigation to overcome resistance to immune checkpoint inhibitors.

scholarly journals On the use of immune checkpoint inhibitors in patients with viral infections including COVID-19

2020 ◽  
Vol 8 (2) ◽  
pp. e001145 ◽  
Author(s):  
Thilo Gambichler ◽  
Judith Reuther ◽  
Christina H Scheel ◽  
Jürgen Christian Becker
Keyword(s):  
Hepatitis B ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Viral Infections ◽  
Checkpoint Inhibitors ◽  
Immunosuppressive Drugs ◽  
Risk Of Infection ◽  
Beneficial Effects ◽  
Available Information

The present review summarizes up-to-date evidence addressing the frequently discussed clinical controversies regarding the use of immune checkpoint inhibitors (ICIs) in cancer patients with viral infections, including AIDS, hepatitis B and C, progressive multifocal leukoencephalopathy, influenza, and COVID-19. In detail, we provide available information on (1) safety regarding the risk of new infections, (2) effects on the outcome of pre-existing infections, (3) whether immunosuppressive drugs used to treat ICI-related adverse events affect the risk of infection or virulence of pre-existing infections, (4) whether the use of vaccines in ICI-treated patients is considered safe, and (5) whether there are beneficial effects of ICIs that even qualify them as a therapeutic approach for these viral infections.

Immunotherapy in Gynecologic Cancers: What We Know Now and Where We Are Headed

2019 ◽  
pp. e126-e140 ◽  
Author(s):  
Kimberly Levinson ◽  
Oliver Dorigo ◽  
Krista Rubin ◽  
Kathleen Moore
Keyword(s):  
Solid Tumors ◽  
Solid Tumor ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Gynecologic Cancer ◽  
Hematologic Malignancies ◽  
Next Generation ◽  
Gynecologic Cancers ◽  
Clinical Benefits

Immunotherapy, mainly in the form of immune checkpoint inhibitors (ICIs), has been transformative in both solid tumor and hematologic malignancies. Patients with previously terminal illnesses have experienced profound responses of great durability with these agents, fueling excitement among patients and providers regarding their use. Unfortunately, the gains seen in some solid tumors have not been replicated in a large percentage of patients with gynecologic cancer. This review focuses on the clinical benefits seen to date, toxicities and management when using ICIs, ways to improve prediction of who should receive immunotherapy, and a discussion of next-generation immunotherapy with cellular therapeutics and how these might relate to gynecologic cancers.

scholarly journals Acute interstitial nephritis, a potential predictor of response to immune checkpoint inhibitors in renal cell carcinoma

2020 ◽  
Vol 8 (2) ◽  
pp. e001198
Author(s):  
Viral Patel ◽  
Roy Elias ◽  
Joseph Formella ◽  
William Schwartzman ◽  
Alana Christie ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Interstitial Nephritis ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Acute Interstitial Nephritis ◽  
First Line ◽  
Improved Outcomes

Immune checkpoint inhibitors (ICIs) such as nivolumab and ipilimumab have improved outcomes in metastatic renal cell carcinoma (mRCC) patients, but they are also associated with immune-related adverse events (irAEs). As observed in melanoma, we hypothesized that patients experiencing an autoimmune reaction directed against the tissue of origin may be more likely to benefit from ICI. Specifically, we asked whether patients with immune-related acute interstitial nephritis (irAIN) exhibited improved outcomes. Using Kidney Cancer Explorer (KCE), a data portal and i2b2-based central database for clinical, pathological and experimental genetic data, we systematically identified all patients with mRCC at UT Southwestern Medical Center (UTSW) from 2014–2018 who received at least one dose of ICI. More recent cases were identified through a provider query. We extracted creatinine (Cr) values at baseline and over the entirety of each patient ICI treatment course using KCE. Patients with ≥ 1.5-fold Cr increase over baseline were investigated. The likelihood of irAIN was determined based on the work-up (biopsy, if available), or by clinical criteria (timing of kidney injury, exclusion of other etiologies, treatment with immunosuppressants and response). We identified 177 mRCC patients who received at least one dose of ICI, 36 of whom had ≥ 1.5-fold increase in Cr over baseline while on treatment. Of those, two had biopsy-proven irAIN and one was clinically diagnosed, resulting in an incidence of 1.7%. One additional biopsy-proven case past 2018 was identified through a provider query, for a total of four patients. Two received combination nivolumab and ipilimumab in the first line, whereas the remaining received nivolumab after first line therapy. irAIN onset ranged from 1.5 to 12 months. All four patients stopped ICI with recovery of renal function, at least partially, three after receiving systemic steroids. Notably, all four patients had a deep response. In conclusion, irAIN is a rare event, but it may portend a higher likelihood of response. One possible explanation is antigenic overlap between normal renal tubular cells and tumor cells.

scholarly journals Lights and Shadows on Managing Immune Checkpoint Inhibitors in Oncology during the COVID-19 Era

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1906
Author(s):  
Chiara Burgaletto ◽  
Oronzo Brunetti ◽  
Antonio Munafò ◽  
Renato Bernardini ◽  
Nicola Silvestris ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Viral Infections ◽  
Checkpoint Inhibitors ◽  
Severe Disease ◽  
Inflammatory Phase ◽  
Clinical Observations ◽  
Increased Risk ◽  
The One

Since the start of the global spread of coronavirus disease (COVID-19) pandemic, cancer patients were identified as a specifically susceptible subgroup of the patient population. Several reports have shown that cancer patients have an increased risk of both contracting the infection and of experiencing a more severe disease course, with a rapidly evolving picture associated with higher mortality. The assumption of cancer patients as “COVID-19 vulnerable” has led, irretrievably, to profound changes in the decision making of oncological treatments. Potential justifications for such concerns encompass the cancer-dependent suppression of the immune response, as well as the influence of administration of systemic anticancer treatments, including chemotherapy and immunotherapy. Nevertheless, to date, it is not clear whether the use of immune checkpoint inhibitors (ICIs) in cancer patients is safe, given their modulating effects on the immune system, or that they may rather conceal detrimental consequences. Theoretically, on the one hand, ICIs may enhance the immunological control of viral infections through their immunostimulating mechanisms; on the other hand, they could contribute to the hyper-inflammatory phase of COVID-19, worsening its clinical outcomes. In this study, we report the foremost clinical observations on the safety of ICI administration in cancer patients affected by COVID-19.

scholarly journals A Contemporary Review of Immune Checkpoint Inhibitors in Advanced Clear Cell Renal Cell Carcinoma

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 919
Author(s):  
Eun-mi Yu ◽  
Laura Linville ◽  
Matthew Rosenthal ◽  
Jeanny B. Aragon-Ching
Keyword(s):  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Vascular Endothelial ◽  
Vegf Inhibitors ◽  
Cell Renal Cell Carcinoma ◽  
Improved Outcomes ◽  
Immune Oncology ◽  
Endothelial Growth Factor

The use of checkpoint inhibitors in advanced and metastatic renal cell carcinomas (RCCs) has rapidly evolved over the past several years. While immune-oncology (IO) drug therapy has been successful at resulting in improved responses and survival, combination therapies with immune checkpoint inhibitors and vascular endothelial growth factor (VEGF) inhibitors have further improved outcomes. This article reviews the landmark trials that have led to the approval of IO therapies, including the Checkmate 214 trial and combination IO/VEGF TKI therapies with Checkmate 9ER, CLEAR, and Keynote-426, and it includes a discussion on promising therapies moving in the future.

Real-world outcomes of treatment with immune checkpoint inhibitors in unique patient cohorts: Elderly, non-caucasian race, poor performance status, obese, chronic viral infections, and autoimmune diseases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2641-2641
Author(s):  
Neil J. Shah ◽  
Shuo Wang ◽  
Aquino Williams ◽  
Melinda Weber ◽  
Brittany Sinclaire ◽  
...  
Keyword(s):  
Viral Infection ◽  
Real World ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Viral Infections ◽  
Checkpoint Inhibitors ◽  
Chronic Viral Infection ◽  
Poor Performance Status ◽  
Chronic Viral Infections ◽  
Ecog Ps

2641 Background: Immune Checkpoint Inhibitors (ICI) have revolutionized current cancer treatment. Nevertheless, outcomes data across various patient cohorts are lacking. To address this knowledge gap, we conducted a comprehensive analysis of real-world data (RWD) that included patient cohorts traditionally underrepresented in clinical trials. Methods: We identified patients (pts) treated with ICI (anti-CTLA-4, anti-PD(L)1 or their combination at 6 US academic and community hospitals from 1/2011 – 4/2018. Clinical data obtained from EHR and CTCAE V4.03 was used to define immune-related adverse events (irAEs). Results: A total of 1332 pts treated with 1443 unique ICI treatments were included in the cohort. The median age was 66 (21-87), Male 58% (827), Caucasian 70% (1004), African American (AA) 16% (232), other race 14% (207), ECOG PS 0,1 79% (1130), chronic viral infection 5% [hepatitis B (24), hepatitis C (32) and HIV (17)], with BMI > 30 22% (287) and autoimmune disease (AID) 15% (215). Lung cancer (NSCLC) 34% (423), and melanoma 27% (389) were top 2 tumor types and nivolumab 38% (544), pembrolizumab 23% (332), and ipilimumab plus nivolumab 12% (180) were the most common ICI treatments. Overall survival (OS) was worse for patients with ECOG ≥2 (0.34 - 0.63) vs. ECOG 0,1 (1.27 - 1.73, P <0.001), and better with AID (1.21 - 2.63) vs. no AID ( 0.90 - 1.24, P=0.01) and Caucasian (1.02 - 1.45) vs AA (0.72 - 1.30, P=0.02). No difference in OS was noted for sex, other races, h/o chronic viral infection or obesity. We performed an analysis of OS and irAEs restricted to NSCLC patients (n=423); (N=447 unique ICI treatments); age >75 27% (120), AA 28% (124), Female 50% (224), ECOG PS ≥2 23% (104), BMI >30 15% (62), chronic viral infections 10% (44), and AID 14% (62). The ICI therapies were nivolumab 55% (245), pembrolizumab 23% (102), and atezolizumab 6% (27) and 16% (others). Data is contained in the table. Conclusions: Overall, in our RWD, OS appeared to be similar across above cohorts except poor OS for pts with ECOG ≥2. irAEs also appeared to be similar across cohorts except less with ECOG ≥2. In NSCLC cohort, we noted similar findings except less irAEs in Male cohort. Prospective studies are needed to confirm the above findings.[Table: see text]

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