Expansion of pharmacist clinical services to optimize the management of immune checkpoint inhibitor toxicities

2019 ◽  
Vol 25 (4) ◽  
pp. 954-960 ◽  
Author(s):  
Catherine E Renna ◽  
Elizabeth N Dow ◽  
Jason J Bergsbaken ◽  
Ticiana A Leal
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Early Recognition ◽  
Management Program ◽  
Cancer Center ◽  
Caregiver Education

Introduction The development of immune checkpoint inhibitors has revolutionized cancer treatment and is now a part of the treatment paradigm for several malignancies. Although immune checkpoint inhibitors are generally well tolerated, treatment is associated with immune-related adverse events, some serious and potentially life threatening. Early identification and prompt appropriate management of immune-related adverse events are crucial to prevent morbidity and mortality. The complexity and severity of immune-related adverse events require interdisciplinary collaboration to optimize care. Patient and caregiver education and continued communication between patients and members of the oncology care team are vital for timely recognition and successful management of immune-related adverse events. The objective of this program is to provide a proof of concept; a pharmacist-led immune checkpoint inhibitor management program will increase early recognition and management of immune-related adverse events through patient and caregiver education and proactively assessing patients for toxicities. Methods At the University of Wisconsin Carbone Cancer Center, we developed and implemented a pharmacist-driven program, referred to as the immune checkpoint inhibitor program, which aimed to ensure patient and caregiver education and continuous monitoring of immune-related adverse events. This program utilized pharmacist–patient encounters to improve patient and caregiver education and follow-up monitoring. The design and implementation are detailed. Pharmacist interventions and patient outcomes were evaluated. Results At interim analysis, 47 patients were enrolled in the program and pharmacists completed 34 interventions on 26 patients. Pharmacists are well positioned to educate patients and caregivers on immune checkpoint inhibitor therapy and provide proactive monitoring to detect immune-related adverse events. We hypothesize that the interventions made by pharmacist may lead to earlier recognition and treatment of immune-related adverse events.

scholarly journals Immune checkpoint inhibitor induced autoimmune encephalitis in a patient with metastatic melanoma

2020 ◽  
Vol 7 (3) ◽  
pp. 1
Author(s):  
Nivedita Sudhekar ◽  
Binoy Yohannan ◽  
Mark Feldman
Keyword(s):  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Early Recognition ◽  
Combined Therapy ◽  
Autoimmune Encephalitis ◽  
The Body

Background: Immune checkpoint inhibitors have changed the therapeutic milieu for patients with metastatic melanoma. However, their use may promote autoimmunity in virtually any organ in the body due to the blockade of intrinsic immune down regulators such as cytotoxic T-lymphocyte antigen- 4 (CTLA-4), programmed cell death 1 (PD1) or its ligand (PDL1). Immune mediated adverse neurological events are rare with these agents, however, and are seen in < 1% of treated patients. We report a patient with immune checkpoint inhibitor associated autoimmune encephalitis, with complete clinical recovery after treatment.Case Report: A 49-year-old female with metastatic melanoma currently on nivolumab therapy but recently on ipilimumab/nivolumab combined therapy presented with a new headache. She also reported associated confusion, loss of balance, personality changes and language difficulty. Magnetic resonance imaging of the brain did not reveal any evidence of metastasis, infarct, meningitis, or encephalitis. Lumbar puncture revealed an elevated protein level and pleocytosis, with a normal glucose level. She was started on empiric glucocorticoid therapy with a presumptive diagnosis of immune checkpoint inhibitor associated autoimmune encephalitis. She improved considerably by day 3 of treatment with complete resolution of neurological symptoms by day 5.Conclusion: Immune checkpoint inhibitors are increasingly important in cancer immunotherapy as they can cause sustained remissions in patients with metastatic melanoma and other malignancies. Because these drugs block immune-regulatory targets, they can lead to enhanced activation of immune system resulting in immune-related adverse events. Autoimmune encephalitis is a rare immune-related adverse event associated with immune checkpoint inhibitors. The incidence of autoimmune encephalitis is higher with combination or sequential CTLA-4 (ipilimumab) and PD1(nivolumab) inhibitor therapy than with monotherapy. With more widespread use of immunotherapy, it is important for clinicians to be aware of this rare and reversible cause of encephalitis. Early recognition and prompt initiation of immunosuppressive therapy with glucocorticoids is essential to enhance neurological recovery.

Immune checkpoint inhibitor induced hepatitis: Risk factors, outcomes, and impact on survival.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14525-e14525
Author(s):  
Abdul Miah ◽  
Songzhu Zhao ◽  
Sandip H. Patel ◽  
Andrew Johns ◽  
Madison Grogan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Comprehensive Cancer Center ◽  
Rank Test ◽  
Cancer Center ◽  
Grade 3

e14525 Background: Immune checkpoint inhibitors (ICIs) have improved the survival of patients with multiple cancer types, however ICI treatment is associated with a unique set of immune-related adverse events (irAEs) that can affect any organ. Few studies have evaluated the risk factors and outcomes of ICI induced hepatitis (ICIH). Methods: We utilized an institutional database of patients with advanced cancers treated with ICI between 2011 and 2017 at The OSU Comprehensive Cancer Center to identify patients with ICIH. Any patient who received at least one dose of ICI alone or in combination with other systemic therapies either as part of clinical trial or standard of care were included. Clinical data were extracted through chart abstraction. irAEs were graded using the Common Terminology Criteria for Adverse Events v5. Overall survival (OS) was calculated from the date of ICI initiation to death from any cause or the date of the last follow-up. OS with 95% confidence intervals were estimated using the Kaplan–Meier method. OS was also evaluated by occurrence of ICIH using the log-rank test. Results: We identified 1,096 patients treated with at least one dose of ICI. Most common cancers included lung (n=224, 20%) and melanoma (n=342, 31%). The most common ICIs were PD1/L1 (n=774, 71%) and CTLA-4 inhibitors (n=195, 18%). ICIH of any grade occurred in 64 (6%) patients. Overall, 46 (71%) were male and median age was 60 years. Severity of hepatitis was grade 1-2 in 30 patients (47%) (Table 1). The incidence of ≥grade 3 ICIH in the entire cohort was 3.1%. Median time to ICIH diagnosis was 63 days. ICIH occurred alone in 24 patients, and co-occurred with other irAEs in 40 patients. The most common co-occurring irAEs were pneumonitis (n=7); colitis (n=15), thyroid abnormality (n=14); and dermatitis (n=15). ICIH was more common in women (p=0.038), in patients treated with combination ICIs (p<0.001), and among patients receiving first line therapy (p=0.018). Patients who developed ICIH had significantly longer OS than patients who did not develop ICIH; there was no difference in OS between patients with ≥grade 3 ICIH vs grade 1-2 (Table). 33 out of 34 patients with ≥grade3 ICIH were treated with steroids; 3 received mycophenolate and one received infliximab. Of patients with ≥grade 3 ICIH, 11 resumed ICI therapy without recurrent ICIH. Conclusions: Female sex, combination immunotherapy, and line of therapy were associated with ICIH. Patients with ICIH had improved clinical outcomes compared to those that did not develop ICIH, even those with higher grade toxicity. Further study is needed to assist in developing risk stratification models and optimal treatment for ICIH. OS of patients with and without immune checkpoint inhibitor hepatitis.[Table: see text]

scholarly journals Endocrinopathies Associated with Immune Checkpoint Inhibitor Cancer Treatment: A Review

2020 ◽  
Vol 9 (7) ◽  
pp. 2033
Author(s):  
Naoko Okura ◽  
Mai Asano ◽  
Junji Uchino ◽  
Yoshie Morimoto ◽  
Masahiro Iwasaku ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Endocrine Disorders ◽  
Appropriate Treatment ◽  
Generic Term ◽  
Pituitary Glands

Treatment with immune checkpoint inhibitors has shown efficacy against a variety of cancer types. The effects of nivolumab and pembrolizumab on lung cancer have been reported, and further therapeutic advances are ongoing. The side effects of immune checkpoint inhibitors are very different from those of conventional cytocidal anticancer drugs and molecular targeted drugs, and they involve various organs such as the digestive and respiratory organs, thyroid and pituitary glands, and skin. The generic term for such adverse events is immune-related adverse events (irAEs). They are relatively infrequent, and, if mild, treatment with immune checkpoint inhibitors can be continued with careful control. However, early detection and appropriate treatment are critical, as moderate-to-severe irAEs are associated with markedly reduced organ function and quality of life, with fatal consequences in some cases. Of these, endocrinopathies caused by immune checkpoint inhibitors are sometimes difficult to distinguish from nonspecific symptoms in patients with advanced cancer and may have serious outcomes when the diagnosis is delayed. Therefore, it is necessary to anticipate and appropriately address the onset of endocrinopathies during treatment with immune checkpoint inhibitors. Here, we present a review of endocrine disorders caused by immune checkpoint inhibitor treatment.

639 Immune-related thyroid dysfunction in patients with existing thyroid dysfunction

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A675-A675
Author(s):  
Francois Kaleta ◽  
Heather Brody ◽  
Praveen Namireddy
Keyword(s):  
New York ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Thyroid Dysfunction ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Increased Risk ◽  
Endocrinological Investigation

BackgroundThyroid dysfunction is a well known side effect of immune checkpoint blockade (ICB) and is one of the most common causes of immune-related adverse events (IRAE). The incidence varies with each individual therapy but generally estimated to be in the range between 6–18% per one study. Hypothyroidism and thyroiditis are the most common manifestations. Initial hyperthyroidism followed by hypothyroidism is another manifestation. Hypothyroidism is more common with an incidence of 10% whereas hyperthyroidism has an incidence of 5%. Less is known about the incidence of worsening thyroid dysfunction in patients with pre-existing thyroid dysfunction treated with ICB.MethodsA retrospective analysis was collected on 370 patients who received immunotherapy from April 2015 to April 2019. Of those, 212 had abnormal thyroid function tests. We analyzed a subgroup of these patients who had baseline thyroid dysfunction for worsening thyroid dysfunction after they were given ICB. Fifty-three patients were included in the analysis and had an abnormal baseline TSH at the start of immunotherapy. Type of immunotherapy, worst TSH, duration between initiation of immunotherapy to worst TSH, treatment type, and grade of abnormality as per Immune Checkpoint Inhibitor Related Adverse Events Common Terminology Criteria for Adverse Events (IRAE-CTCAE) were also recorded. Analysis was done for patients to compare likelihood of worsening TSH resulting in change in treatment for thyroid disorder.ResultsOf the identified patients (N=53) with abnormal TSH screening values outside of the institution’s normal reference range 0.35 - 4.95 uIU/ml, 45.7% (N=16) were hypothyroid and 54.3% (N=19) were hyperthyroid at baseline. Of those who were hypothyroid, 50% (N=8) had worsening TSH and 50% (N=8) had unchanged TSH during treatment. Of those who were hyperthyroid, 31.6% (N=6) had unchanged TSH, 52.6% (N=10) had worsened TSH, and 15.8% (N=3) had normalization of TSH compared to baseline. Overall 26.4% had worsening and of those 11.3% required treatment change.ConclusionsThyroid dysfunction is one of the most common IRAE’s associated with immune checkpoint inhibitors. Little is known about the impact of immunotherapy on patients with existing thyroid dysfunction. Patients who have underlying thyroid dysfunction are at an increased risk for worsening thyroid dysfunction with the use of ICB but though not unduly above the risk general population. Of those with change, only a modest percentage required an alteration of their endocrine therapy. Of interest, our data suggests a potential increased risk in patients with baseline hyperthyroidism compared to hypothyroidism which may be clinically relevant.Ethics ApprovalThe study was approved by ECU Brody School of Medicine Institution’s Ethics Board, approval number 19-000710.ReferencesBarroso-Sousa R, Barry WT, Garrido-Castro AC, et al. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA oncology. 2018;4:173–182.Fessas P, Possamai LA, Clark J, et al. Immunotoxicity from checkpoint inhibitor therapy: clinical features and underlying mechanisms. Immunology. 2019; 2020;159:167–177.Brody HM, Macherla S, Bulumulle A, Namireddy P, Cherry CR. The real-world incidence of immunotherapy-related thyroid dysfunction: A retrospective analysis of a single center’s experience over five years. Journal of clinical oncology. 2020;38:98–98.Iyer PC, Cabanillas ME, Waguespack SG, et al. Immune-Related Thyroiditis with Immune Checkpoint Inhibitors. Thyroid (New York, N.Y.). 2018;28:1243–1251.Presotto EM, Rastrelli G, Desideri I, et al. Endocrine toxicity in cancer patients treated with nivolumab or pembrolizumab: results of a large multicentre study. Journal of endocrinological investigation. 2019; 2020;43:337–345.Chalan P, Di Dalmazi G, Pani F, De Remigis A, Corsello A, Caturegli P. Thyroid dysfunctions secondary to cancer immunotherapy. Journal of endocrinological investigation. 2017; 2018;41:625–638.Mangla A, Paydary K, Yadav U, Liu J, Lad TE. Predictors and outcomes of thyroid dysfunction with immunotherapy: A single institution observational experience. Journal of clinical oncology. 2019;37:e14134-e14134.Basak EA, van der Meer, Jan W M, Hurkmans DP, et al. Overt Thyroid Dysfunction and Anti-Thyroid Antibodies Predict Response to Anti-PD-1 Immunotherapy in Cancer Patients. Thyroid (New York, N.Y.). 2020;30:966–973.Kassi E, Angelousi A, Asonitis N, et al. Endocrine-related adverse events associated with immune-checkpoint inhibitors in patients with melanoma. Cancer medicine (Malden, MA). 2019;8:6585–6594.

Characteristics of hospitalizations among patients receiving immune checkpoint inhibitors at a community teaching hospital

2019 ◽  
Vol 26 (1) ◽  
pp. 60-66
Author(s):  
Brendan Rasor ◽  
Rachel Henderson ◽  
Kin Chan
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Cancer Type ◽  
Preventable Admissions ◽  
The Impact ◽  
Reason For Admission

Purpose As immune checkpoint inhibitors continue to acquire new indications, it is important to understand the impact their use has on patients. This study adds to current literature by presenting an analysis of hospitalizations in this population. The primary objective was to assess the reasons for an emergency department visit or hospital admission in patients who receive immune checkpoint inhibitors. Secondary objectives included identifying the frequency of suspected or confirmed immune related adverse events, types of immune related adverse events, number of preventable admissions, duration of immunotherapy, and length of stay. Methods This study was a retrospective, multi-center, chart review of patients hospitalized after receiving an immune checkpoint inhibitor. The population included patients aged 18 and above who received at least one dose of an immune checkpoint inhibitor at a network facility and had a documented admission within one year following the initiation of immunotherapy. Descriptive statistics were performed along with inferential comparisons and a Poisson regression to determine if the immune checkpoint blocker or cancer type predicted admission or reason for admission. Results The 99 patients who met inclusion criteria had a total of 202 admissions. Of these patients, 56 (56.6%) had multiple admissions within the year following initiation of immunotherapy. The most common diagnoses on initial admissions were shortness of breath, pain, and pneumonia. A total of 104 admissions (51.5%) were considered potentially preventable. Suspected or confirmed immune related adverse events were identified in 15.6% of all admissions. There were no significant predictors of admissions or reason for admission. Conclusion Reasons for admission in the study population were comparable to those identified in the general cancer population, with immune related adverse events being associated with a minority of both total and potentially preventable admissions.

Association of immune-related adverse events with immune checkpoint inhibitor efficacy in pancancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14087-e14087 ◽  
Author(s):  
Qiyun Ou ◽  
Yunfang Yu ◽  
Haitao Zhong ◽  
Anlin Li ◽  
Yongjian Chen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Advanced Cancer ◽  
Immune Checkpoint ◽  
Conventional Therapy ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Coefficient Of Determination

e14087 Background: Immune-related adverse events (irAEs) have been shown to be associated with the efficacy of immune checkpoint inhibitors in patients with advanced cancer, but the reported effect sizes have varied greatly in previous trials. We did a meta-analysis to assess immune checkpoint inhibitors efficacy and further explored the correlation of irAEs with efficacy in cancer. Methods: We systematically searched database inception to January, 2019 for randomized trials of immune checkpoint inhibitor in patients with advanced cancer that had available data for overall survival (OS) and progression-free survival (PFS), and irAEs. We calculated the pooled hazard ratios (HRs) and 95% confidence intervals [CIs] using a random-effects model, and assessed the association between the irAEs and PFS or OS using coefficient of determination ( R²). The PROSPERO registry number is CRD42017075610. Results: Thirty eight trials with 19,521 patients were included. Compared with conventional therapy, anti-PD-1 or PD-L1 combined with conventional therapy significantly enhanced survival (HR = 0.62, 95% CI 0.53 to 0.72 for PFS; HR = 0.71, 95% CI 0.58 to 0.87 for OS), and anti-PD1 or PD-L1 combined with anti-CTLA4 (HR = 0.75, 95% CI 0.63 to 0.90 for PFS). Anti-CTLA4 plus conventional therapy prolonged PFS (HR = 0.80, 95% CI 0.72 to 0.89) and OS (HR = 0.80, 95% CI 0.66 to 0.96) than conventional therapy alone. Anti-PD1 or PD-L1 outperformed anti-CTLA4 on OS (HR = 0.68, 95% CI 0.57 to 0.81). Significant correlation between treatment efficacy and irAEs was only identified in pneumonitis ( R2 0.59, P = 0.026 for PFS) and diarrhea ( R2 0.22, P = 0.006 for OS). Conclusions: We recommended the concurrent use of immune checkpoint inhibitor and conventional therapy or dual immunotherapy as the most appropriate regimens for advanced cancer. Furthermore, development of pneumonitis and diarrhea were associated with survival outcome of immune checkpoint inhibitors in patients with advanced cancer.

New onset diabetes with ketoacidosis following nivolumab immunotherapy: A case report and review of literature

2020 ◽  
pp. 107815522094394
Author(s):  
Lukas Delasos ◽  
Christopher Bazewicz ◽  
Aleksandra Sliwinska ◽  
Nerea Lopetegui Lia ◽  
James Vredenburgh
Keyword(s):  
Diabetes Mellitus ◽  
Case Report ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Programmed Death ◽  
Checkpoint Inhibitor Therapy

Introduction Immune-checkpoint inhibitors have become an increasingly popular form of systemic therapy for cancer treatment. Their use has proven to be so effective that certain regimens have gained approval as first-line therapy for various solid tumor types. The most common and well-studied forms of immunotherapy include agents that target cytotoxic T-lymphocyte antigen-4, programmed death-1, and programmed death ligand-1. These therapies act by blocking signaling between immune cells and cancer cells which subsequently augment T cell-mediated destruction of tumor cells. Case report Here, we report a case of a 77-year-old black male with no history of or risk factors for diabetes mellitus who presented with acute onset of diabetic ketoacidosis after beginning immunotherapy with nivolumab for metastatic high-grade neuroendocrine tumor of the lung. He was admitted and treated for diabetic ketoacidosis but required prolonged use of an insulin infusion with frequent need of intravenous dextrose due to labile blood sugars. The patient was eventually discharged and discontinued further immunotherapy with nivolumab. Discussion Due to the unique mechanisms by which immune-checkpoint inhibitors cause immune-mediated destruction of tumor cells, clinicians may be challenged with their associated autoimmune complications referred to as immune-related adverse events. In particular, the incidence of endocrine dysfunction following immune-checkpoint inhibitor therapy is approximately 12%, with the development of insulin-dependent diabetes mellitus being a rare complication. Increasing awareness of immune-related adverse events is essential for the early recognition and effective management of patients who present with life-threatening complications related to immune-checkpoint inhibitor therapy.

scholarly journals Nivolumab-induced hypothyoidism with consequent hypothyroid related myopathy

2019 ◽  
Vol 26 (1) ◽  
pp. 224-227 ◽  
Author(s):  
Eric D Johnson ◽  
Katie Kerrigan ◽  
Katerina Butler ◽  
Shiven B Patel
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Hormone Replacement ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Anti Tumor Activity

Purpose Nivolumab is a fully human IgG4 programmed death 1 immune checkpoint inhibitor (ICI) antibody that has anti-tumor activity by selectively blocking the interaction of the programmed death 1 receptor with its two known programmed death ligands PD-L1 and PD-L2. In doing so, this immune checkpoint inhibitor removes the negative signal stifling T cell activation and proliferation within the tumor microenvironment and demonstrates favorable antitumor activity. Case report We report an interesting case of immune checkpoint inhibitor-induced primary hypothyroidism with associated hypothyroid myopathy in a young patient with surgically resected stage IIIB melanoma receiving adjuvant nivolumab. He presented 12 weeks into therapy with severe myalgias, arthralgias, and intermittent disequilibrium of unclear etiology. Laboratory evaluation demonstrated a significant elevation in thyroid stimulating hormone and creatine kinase with an undetectable free T4 with standard laboratory measurement. With thyroid hormone replacement therapy alone, he had rapid improvement in his musculoskeletal symptoms and laboratory parameters over a three-week period. Discussion This case emphasizes the serious nature of endocrine immune-related adverse events in patients receiving immune checkpoint inhibitors. Additionally, it highlights that unlike most other immune-related adverse events, endocrine immune-related adverse events can generally be managed with adequate hormone replacement alone with swift improvements in symptoms. This allows patients to continue immune checkpoint inhibitors safely without immunosuppression which may dampen the anti-tumor activity of these agents. Conclusion This case highlights the importance of early recognition and the appropriate management of endocrine immune-related adverse events to maximize patient safety and good outcomes.

scholarly journals Non-bullous pemphigoid associated with immune checkpoint inhibitor treatment

2021 ◽  
Author(s):  
Akiyoshi Senda ◽  
Takaya Komori ◽  
Yoshihiro Ishida ◽  
Teruasa Murata ◽  
Atsushi Otsuka ◽  
...  
Keyword(s):  
Adverse Events ◽  
Bullous Pemphigoid ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Disease Course ◽  
Latent Disease ◽  
Inhibitor Treatment

Though a variety of immune-related adverse events of immune checkpoint inhibitors (ICIs) including bullous pemphigoid have been reported, non-bullous pemphigoid (NBP) associated with ICI therapy was scarcely reported. We present a case of NBP with a long latent disease course without diagnosis during nivolumab, an ICI therapy.

Efficacy of immunotherapy in hepatocholangiocarcinoma (HCC-CC): Proof of concept.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16194-e16194
Author(s):  
Osama Diab ◽  
Maloree Khan ◽  
Saqib Abbasi ◽  
Anwaar Saeed ◽  
Anup Kasi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
First Line ◽  
Liver Cancers ◽  
First Line Treatment

e16194 Background: Hepatocholangiocarcinoma (HCC-CC) is a rare form of cancer with a poor prognosis. Of all primary liver cancers, the incidence of HCC-CC ranges from 0.4 to 14.2%. HCC-CC is a mixed carcinoma with findings of both hepatocellular carcinoma and cholangiocarcinoma. Immune checkpoint inhibitors are a potent first line treatment in hepatocellular carcinoma with multiple clinical trial showing effectiveness in cholangiocarcinoma. HCC-CC has limited proven treatment options as patients are generally excluded from clinical trials. In this study we reviewed outcomes of patients with HCC-CC who received immune checkpoint inhibitor in a single center. Methods: Records of patients who had a pathological confirmed HCC-CC by a subspecialized hepatic pathologist at the University of Kansas medical center were reviewed. We identified 6 patients with locally advanced unresectable or metastatic HCC-CC that received immune checkpoint inhibitor between February 2017 and January 2021. Baseline characteristics were obtained, as well as best response, line of therapy, and duration of response. Results: Of the six patients 4 (66%) received PD-1 inhibitor alone and 2 (34%) received combination therapy with CTLA-4 inhibitor for the treatment of HCC-CC. There were 3 (50%) females and 6 (100%) with prior hepatitis C infection. four (66%) patients had metastatic disease and 2 had locally unresectable advanced disease. Objective response rate was 83.3%. One patient achieved complete response and had a treatment holiday after receiving treatment for 2 years, and restarted immunotherapy upon relapse. Four patients had a partial response, of which two passed away after disease progression. One patient had stable disease on 2 different lines of immunotherapy then progressed. Of those who responded, one patient received immunotherapy, 3 (50%) received liver directed therapy and two received chemotherapy or Lenvatinib as first line treatment (Table). Conclusions: Immune checkpoint inhibitors demonstrate potential activity in patients with HCC-CC without unexpected side effect in this unmet need high-risk population. Larger studies are needed to confirm activity and efficacy in this setting.[Table: see text]

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