SAT0540 ONE-YEAR OUTCOMES AFTER RHEUMATIC IMMUNE-RELATED ADVERSE EVENTS FROM CHECKPOINT INHIBITORS

Background:Description and initial management of rheumatic immune-related adverse-events (irAEs) from cancer immunotherapies have been reported by several groups but to date, few studies have evaluated the long-term outcomes and management of rheumatic irAEs (1).Objectives:To describe the long-term management and assess the one-year outcomes of patients who experienced rheumatic immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICI).Methods:This was a single-centre prospective observational study including patients referred for musculoskeletal symptoms while treated with ICI. After baseline rheumatological evaluation defining the clinical entity presented, follow-up visits were organised according to the type and severity of irAE. At one year, persistence of irAE, ongoing treatment, as well as cancer outcomes were assessed.Results:63 patients were included between September 2015 and June 2018. 24 patients (38%) presented with non-inflammatory musculoskeletal conditions managed with short-term symptomatic treatment and did not require specific follow-up. 39 patients (62%) experienced inflammatory manifestations, mimicking either rheumatoid arthritis (RA, n=19), polymyalgia rheumatica (PMR, n=16), psoriatic arthritis (PsA, n=3) and one flare of a preexisting axial spondyloarthritis. Overall, 32 patients (82%) received systemic glucocorticoids, with a median rheumatic dosage of 15mg/day (range: 5-60mg/day). None of the patients had to permanently discontinue ICI therapy for rheumatic irAE. 20 patients (67%) were still receiving glucocorticoids at one year, with a median dosage of 5mg/day (range: 2-20mg/day). Glucocorticoids were more frequently discontinued for patients with RA-like condition (44%) than PMR-like condition (23%), but no other predictive factor of glucocorticoids withdrawal could be identified. At one year, overall survival and progression-free survival were comparable between patients who were still receiving glucocorticoids for rheumatic irAE and patients who have discontinued. Eight patients required csDMARDs.Conclusion:At one year, a majority of patients required long-term low-dose glucocorticoids for chronic rheumatic irAE, which seems not altering oncological control.References:[1]Braaten TJ, Brahmer JR, Forde PM, et al. Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation. Ann Rheum Dis. 2019 Sep 20.Disclosure of Interests:None declared

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Correlation between immune-related adverse events and prognosis in patients with gastric cancer treated with nivolumab

BMC Cancer ◽

10.1186/s12885-019-6150-y ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 22

Author(s):

Ken Masuda ◽

Hirokazu Shoji ◽

Kengo Nagashima ◽

Shun Yamamoto ◽

Masashi Ishikawa ◽

...

Keyword(s):

Gastric Cancer ◽

Adverse Events ◽

Immune Checkpoint ◽

Clinical Benefit ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Progression Free Survival ◽

Motor Neuropathy ◽

Metastatic Sites

Abstract Background Recent studies have shown that immune-related adverse events (irAEs) caused by immune checkpoint inhibitors were associated with clinical benefit in patients with melanoma or lung cancer. In advanced gastric cancer (AGC) patients, there have been few reports about the correlation between irAEs and efficacy of immune checkpoint inhibitors. In this study, we retrospectively investigated the correlation between irAEs and efficacy in AGC patients treated with nivolumab. Methods The subjects of this study were AGC patients received nivolumab monotherapy between January 2015 and August 2018. IrAEs were defined as those AEs having a potential immunological basis that required close follow-up, or immunosuppressive therapy and/or endocrine therapy. We divided the patients who received nivolumab into two groups based on occurrence of irAEs; those with irAEs (irAE group) or those without (non-irAE group). We assessed the efficacy in both groups. Results Of the 65 AGC patients that received nivolumab monotherapy, 14 developed irAEs. The median time to onset of irAEs was 30.5 days (range 3–407 days). Median follow-up period for survivors was 32 months (95% CI, 10.8 to 34.5). The median progression-free survival was 7.5 months (95% CI, 3.6 to 11.5) in the irAE group and 1.4 months (95% CI, 1.2 to 1.6) in the non-irAE group (HR = 0.11, p < 0.001). The median overall survival was 16.8 months (95% CI, 4.4 to not reached) in the irAE group and 3.2 months (95% CI, 2.2 to 4.1) in the non-irAE group (HR = 0.17, p < 0.001). Multivariate analysis demonstrated that number of metastatic sites ≥2 (HR = 2.15; 95% CI, 1.02 to 4.54), high ALP level (HR = 2.50; 95% CI, 1.27 to 4.54), and absence of irAEs (HR = 9.54, 95% CI, 3.34 to 27.30 for yes vs. no) were associated with a poor prognosis. The most frequent irAEs was diarrhea/colitis (n = 5). Grade 3 adverse events were observed in 6 patients; hyperglycemia (n = 2), diarrhea/colitis (n = 1), adrenal insufficiency (n = 1), aspartate aminotransferase increased (n = 1), peripheral motor neuropathy (n = 1). There were no grade 4 or 5 adverse events related to nivolumab. Conclusions Development of irAEs was associated with clinical benefit for AGC patients receiving nivolumab monotherapy.

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Phenotypic Differences in Thyroid Immune Related Adverse Events Following Treatment With Immune Checkpoint Inhibitors

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1790 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A876-A877

Author(s):

Christopher Alan Muir ◽

Alexander M Menzies ◽

Roderick John Clifton-Bligh ◽

Georgina V Long ◽

Richard A Scolyer ◽

...

Keyword(s):

Adverse Events ◽

Immune Checkpoint ◽

Thyroid Dysfunction ◽

Cancer Survival ◽

Checkpoint Inhibitors ◽

Progression Free Survival ◽

Organ Systems ◽

Euthyroid Hyperthyroxinemia ◽

Overt Hyperthyroidism

Abstract Background: Thyroid toxicity is common following immune checkpoint inhibitor (ICI) treatment. Published studies estimate the incidence at 10-20%, although rates vary widely between different ICIs. The etiology of ICI-associated thyroid immune related adverse events (irAEs) is unknown & not all patients develop a classic thyroiditis-like presentation of transient hyperthyroidism followed by a hypothyroid phase. Only small observational cohorts have been reported & the clinical & biochemical features of thyroid irAEs have not been well characterized. The current study aimed to describe thyroid irAEs in a large cohort of patients with melanoma. Methods: We reviewed outcomes in a prospective cohort of adult patients undergoing ICI treatment for advanced melanoma. Thyroid function was measured at baseline & at regular intervals during treatment. Thyroid irAEs were defined as new biochemical thyroid dysfunction developing over the course of routine follow-up. Results: Thyroid irAEs occurred in 518 of 1246 (42%) patients. Median follow-up was 11.3 months. Multiple patterns of thyroid-irAEs were observed, such as hyperthyroidism (subclinical or overt) in 31%, hypothyroidism in 8%, & euthyroid hyperthyroxinemia, hypothyroxinemia & isolated low FT3 syndrome each in 1% of participants. Thyroid irAEs were more frequent following combination (CTLA-4 + PD-1) ICI treatment (56%) than following PD-1 (38%) or CTLA-4 (25%) based monotherapies (p=0.001). The severity of thyroid irAEs differed by ICI, with higher rates of overt (vs. subclinical) thyroid dysfunction following combination ICI treatment (47%) relative to PD-1 (37%) & CTLA-4 (19%) monotherapies (p=0.001). Younger age (OR 0.88 per 10-yrs; 95% CI 0.81-0.96), female sex (OR 1.62; 95% CI 1.27-2.08) & combination ICI-treatment (vs. CTLA-4, OR 3.76, 95% CI 2.49-5.75; vs. PD-1, OR 1.90, 95% CI 1.45-2.49) were associated with higher odds of thyroid irAE. Time to onset of thyroid dysfunction was shorter in patients with overt hyperthyroidism relative to other types of thyroid irAE (log rank p=0.001). Overt hyperthyroidism was associated with increased irAEs in other organ systems (colitis, hepatitis, etc), increased irAE severity & increased multi-system irAEs than euthyroid patients or patients with other subtypes of thyroid irAE (p=0.003). Overt hyperthyroidism was also associated with improved progression free survival (HR 0.57; 95% CI 0.39-0.84; p=0.005) & overall survival (HR 0.68; 95% CI 0.49-0.94; p=0.02). No benefit to cancer survival was observed with other thyroid irAE subtypes. Conclusions: Thyroid irAEs were common. Combination ICI treatment resulted in more frequent, more severe, & earlier onset thyroid irAEs. Of thyroid irAE subtypes, overt hyperthyroidism was uniquely associated with increased immune responsiveness, as evidenced by higher incidence of extra-thyroidal irAEs & improvements in cancer survival.

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Correlation between immune-related adverse events and prognosis in patients with gastric cancer treated with nivolumab.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.4049 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 4049-4049 ◽

Cited By ~ 1

Author(s):

Ken Masuda ◽

Hirokazu Shoji ◽

Kengo Nagashima ◽

Shun Yamamoto ◽

Masashi Ishikawa ◽

...

Keyword(s):

Gastric Cancer ◽

Adverse Events ◽

Immune Checkpoint ◽

Clinical Benefit ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Progression Free Survival ◽

Motor Neuropathy ◽

Progression Of Disease

4049 Background: Recent studies have shown that immune-related adverse events (irAEs) caused by immune checkpoint inhibitors were associated with clinical benefit in patients with melanoma or lung cancer. In advanced gastric cancer (AGC) patients, there have been few reports about the correlation between irAEs and efficacy of immune checkpoint inhibitors. Therefore, in this study, we retrospectively investigated the correlation between irAEs and efficacy in AGC patients treated with nivolumab. Methods: The subjects of this study were AGC patients that had received nivolumab monotherapy between January 2015 and August 2018. IrAEs were defined as those AEs having a potential immunological basis that required close follow-up, or immunosuppressive therapy and/or endocrine therapy. We divided the patients who received nivolumab into two groups based on occurrence of irAEs; those with irAEs (irAE group) or those without (non-irAE group). We assessed the efficacy in both groups. Results: Of the 65 AGC patients that received nivolumab monotherapy, 14 developed irAEs. The median time to onset of irAEs was 30.5 days (range 3–407 days). Median follow-up period for survivors was 32 months (95% CI, 10.8 to 34.5). The median progression-free survival was 7.5 months (95% CI, 3.6 to 11.5) in the irAE group and 1.4 months (95% CI, 1.2 to 1.6) in the non-irAE group (HR = 0.11, p < 0.001). The median overall survival was 16.8 months (95% CI, 4.4 to not reached) in the irAE group and 3.2 months (95% CI, 2.2 to 4.1) in the non-irAE group (HR = 0.17, p < 0.001). Multivariate analysis demonstrated that high ALP level (HR = 2.88; 95% CI, 1.51 to 5.51) and absence of irAEs (HR = 3.06, 95% CI, 3.06 to 23.46 for yes vs. no) were associated with a poor prognosis. The most frequent irAEs was diarrhea/colitis (n = 5). Grade 3 adverse events were observed in 6 patients; hyperglycemia (n = 2), diarrhea/colitis (n = 1), adrenal insufficiency (n = 1), increased aspartate aminotransferase increased (n = 1), peripheral motor neuropathy (n = 1). One of the 14 patients experienced the irAE after discontinuation of nivolumab due to progression of disease. There were no grade 4 or 5 adverse events related to nivolumab. Conclusions: Development of irAEs was associated with clinical benefit for AGC patients receiving nivolumab monotherapy.

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Intracranial 131I-chTNT Brachytherapy in Patients with Deep-Seated Glioma: A Single-center Experience with 10-Year Follow-up from China

Nuklearmedizin ◽

10.1055/a-1429-1967 ◽

2021 ◽

Author(s):

Ming Zhao ◽

Xiangping Fu ◽

Zhiwen Zhang ◽

Anmin Li ◽

Xiaopeng Wang ◽

...

Keyword(s):

Overall Survival ◽

Adverse Events ◽

Progression Free Survival ◽

Tumor Diameter ◽

Free Survival ◽

Single Center Experience ◽

Long Term Follow Up ◽

One Year

Abstract Objective The intracranial brachytherapy has been applied for decades, however, no results with long-term follow-up have been reported. This study investigated the long-term efficiency of intra-tumoral injection of 131I-chTNT in patients with deep-seated glioma. Method Thirty-five patients undergoing 131I-chTNT brachytherapy between December 2004 and May 2009 were enrolled. 131I-chTNT was injected at a dose of 1.5 mCi/cm3 at an interval of 1 month for consecutive 3 times. Serial ECT scan and MRI were performed during follow-up. Progression-free survival (PFS) and overall survival (OS) were analyzed. Adverse reactions were graded with WHO Toxicity Grading Scale for determining the severity of adverse events. Results ECT scan showed that enhanced accumulation of radioactive agents in the tumor lasted for more than 30 days. Three months after final injection, tumor complete remission (CR) was observed in 4 patients (11.4 %), partial remission (PR) in 11 cases (31.4 %), stable disease (SD) in 10 cases (28.6 %) and progressive disease (PD) in 10 cases (28.6 %). At 6-month, CR, PR, SD and PD were 2, 6, 12 and 15 respectively. After 10 years of follow-up, median progression-free survival (PFS) and overall survival (OS) were 5.4 and 11.4 months. One-year survival was 45.7 %, two and five-year survival was 8.6 %, ten-year survival was 5.7 %. Multivariate analysis showed that pathological grade and tumor diameter were independent prognostic factors for PFS and OS. Grade I–II adverse events occurred after drug injection, including nausea, fever, headache, hairloss and fatigue. Conclusion 131I-chTNT intracranial brachytherapy is efficient and safe for patients with deep-seated glioma. It is a reliable option for inoperable glioma patients.

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FRI0494 RHEUMATIC IMMUNE RELATED ADVERSE EVENTS OF CHECKPOINT INHIBITORS: A RETROSPECTIVE REVIEW OF 70 PATIENTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.772 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 845.2-846

Author(s):

T. Lenfant ◽

L. Calabrese ◽

C. Calabrese

Keyword(s):

Adverse Events ◽

Prospective Studies ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Clinical Aspects ◽

Link Type ◽

Conventional Dmards

Background:Immune Checkpoint inhibitors (ICI) have revolutionized cancer therapy by achieving remarkable survival benefits however, at the cost of a myriad of immune-related adverse events (irAEs)[1]. Rheumatic irAE can develop in 5-10% of patients although the true incidence is unknown given the lack of prospective studies [2]. Symptoms are heterogenous and probably underreported with few data available about their management and outcome [3].Objectives:To describe the clinical, biological, and radiological features of the largest cohort of rheumatic irAEs from ICI along with their therapeutic management, outcome and follow-up in real-world practice.Methods:A referral process for emergent rheumatic irAEs was initiated in February 2016 between the oncology and rheumatology departments at the Cleveland Clinic Foundation. All patients were evaluated by authors CC and/or LHC. Patients’ characteristics were retrospectively collected from medical charts after IRB approval.Results:70 patients referred for one or more rheumatic irAEs between February 2016 and January 2020 were included. 66% were male, median age was 60.8 years. Among them, 24 (34%) had pre-existing rheumatic complaints. Melanoma was the most frequent malignancy (56%). ICI therapy included anti-CTLA4 (40%), anti-PD1/L1 (79%), and dual therapy ipilimumab/nivolumab (41%). Rheumatic irAE occurred in a median 4 months after ICI initiation, with phenotypes including inflammatory arthritis (32 patients), sicca-like symptoms (12), polymyalgia rheumatica-like (7), and myositis (2). Oral, intravenous or intraarticular glucocorticoids (GC) were administered to 54 patients (77%). Of these 54 patients, 22 (41%) required long term GC, 19 had bone density scan and 15 received pneumocystis (PJP) prophylaxis. One PJP case, 1 osteoporotic fracture and 2 avascular necrosis cases were reported. 16 patients received conventional DMARDS (23%) and 9 received biologics (13%). ICI therapy was held for rheumatic irAE in 31% of cases and for another systemic irAE in 29%. Median follow-up was 13.6 months, at end of follow-up 51 patients were still on treatment for rheumatic irAE and 41% of them were still symptomatic despite ongoing treatment.Conclusion:Rheumatic irAEs are heterogeneous and often chronic requiring prolonged immunomodulatory therapy. Prospective studies are required to define optimal management of rheumatic irAEs that maintain long-term oncologic outcomes.References:[1]Suarez-Almazor ME, Kim ST, Abdel-Wahab N, Diab A. Review: Immune-Related Adverse Events With Use of Checkpoint Inhibitors for Immunotherapy of Cancer. Arthritis Rheumatol 2017;69:687–99.https://doi.org/10.1002/art.40043.[2]Abdel-Wahab N, Suarez-Almazor ME. Frequency and distribution of various rheumatic disorders associated with checkpoint inhibitor therapy. Rheumatol (United Kingdom) 2019;58:vii40–8.https://doi.org/10.1093/rheumatology/kez297.[3]Kostine M, Rouxel L, Barnetche T, Veillon R, Martin F, Dutriaux C, et al. Rheumatic disorders associated with immune checkpoint inhibitors in patients with cancer-clinical aspects and relationship with tumour response: a single-centre prospective cohort study. Ann Rheum Dis 2018;77:393–8.https://doi.org/10.1136/annrheumdis-2017-212257.Disclosure of Interests:Tiphaine Lenfant: None declared, Leonard Calabrese Consultant of: AbbVie, GSK, Bristol-Myers Squibb, Genentech, Janssen, Novartis, Sanofi, Horizon, Crescendo, and Gilead, Speakers bureau: Sanofi, Horizon, Crescendo, Novartis, Genentech, Janssen, and AbbVie, cassandra calabrese Consultant of: AbbvieGSK, Speakers bureau: Sanofi-Genzyme

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The association between albumin-globulin ratio (AGR) and survival in patients treated with immune checkpoint inhibitors

Cancer Biomarkers ◽

10.3233/cbm-210349 ◽

2021 ◽

pp. 1-11

Author(s):

Deniz Can Guven ◽

Oktay Halit Aktepe ◽

Melek Seren Aksun ◽

Taha Koray Sahin ◽

Gozde Kavgaci ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Multivariate Analyses ◽

Checkpoint Inhibitors ◽

Progression Free Survival ◽

Free Survival ◽

Patients With Cancer ◽

Early Progression ◽

Term Benefit

BACKGROUND: The albumin-globulin ratio (AGR) could be a prognostic biomarker in patients with cancer, although the data is limited in patients treated with immune-checkpoint inhibitors (ICIs). OBJECTIVES: We aimed to evaluate the association between AGR and survival in ICI-treated patients. METHODS: The data of 212 advanced-stage patients were retrospectively evaluated in this cohort study. The association between AGR with overall (OS) and progression-free survival (PFS) were evaluated with multivariate analyses. Additionally, receptor operating curve (ROC) analysis was conducted to assess the AGR’s predictive power in the very early progression (progression within two months) and long-term benefit (more than twelve months survival). RESULTS: The median AGR was calculated as 1.21, and patients were classified into AGR-low and high subgroups according to the median. In the multivariate analyses, patients with lower AGR (< 1.21) had decreased OS (HR: 1.530, 95% CI: 1.100–2.127, p= 0.011) and PFS (HR: 1.390, 95% CI: 1.020–1.895, p= 0.037). The area under curve of AGR to detect early progression and long-term benefit were 0.654 (95% CI: 0.562–0.747, p= 0.001) and 0.671 (95% CI: 0.598–0.744, p< 0.001), respectively. CONCLUSIONS: In our experience, survival with ICIs was impaired in patients with lower AGR. Additionally, the AGR values could detect the very early progression and long-term benefit ICIs.

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Promising Immunotherapy in Metastatic Testicular Sex Cord Stromal Tumours After First-Line Chemotherapy

Frontiers in Immunology ◽

10.3389/fimmu.2021.720359 ◽

2022 ◽

Vol 12 ◽

Author(s):

Bingqing Shang ◽

Chuanzhen Cao ◽

Weixing Jiang ◽

Hongzhe Shi ◽

Xingang Bi ◽

...

Keyword(s):

Adverse Events ◽

Checkpoint Inhibitors ◽

Objective Response ◽

Chemotherapy Resistance ◽

Progression Free Survival ◽

Retroperitoneal Lymph Node Dissection ◽

First Line ◽

Experienced Grade ◽

Line Chemotherapy

BackgroundTesticular sex cord stromal tumours (TSCSTs) are rare, with few studies focusing on the metastatic TSCST prognosis. The value of treatments, including radical orchiectomy (RO) and retroperitoneal lymph node dissection (RPLND), in preventing metastasis is controversial. Additionally, metastatic TSCSTs are resistant to chemotherapy. We aimed to assess the effectiveness and safety of immunotherapy in metastatic TSCSTs after first-line chemotherapy.MethodsWe retrospectively screened patients with testicular tumours undergoing testis surgery between January 2005 and January 2019. Patients with TSCSTs who had undergone testis-sparing surgery (TSS) or RO were identified. The malignant type was defined as metastasis confirmed by pathology. Treatment responses, progression-free survival (PFS), overall survival (OS) and safety were analysed.ResultsAmong the 494 testicular tumour patients who received TSS or RO, 11 (2.2%) patients with histologically proven TSCSTs were identified. At the last follow-up, 7 patients survived without tumours, and 4 patients developed metastasis and received first-line cisplatin-based chemotherapy, with 1 of them achieving an objective response. Their PFS times were 1.5, 2.2, 9.0, and 17.0 months, respectively. Two patients received immune checkpoint inhibitors (ICIs) after developing chemotherapy resistance and achieved a partial response up to the last follow-up; one of them experienced Grade 1 adverse events, and the other experienced Grade 2 adverse events during immunotherapy. The median OS time of the 4 patients with metastatic TSCSTs was 32 months.ConclusionsTSCSTs are rare, and most are benign with a good prognosis. ICIs represent a promising option for improving clinical outcomes in metastatic TSCSTs.

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Abstract 14600: Pre-existing Autoimmune Disease and the Risk for Cardiovascular and Non-cardiovascular Immune Mediated Adverse Events With Immune Checkpoint Inhibitors

Circulation ◽

10.1161/circ.142.suppl_3.14600 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Charlotte Lee ◽

Zsofia D Drobni ◽

Amna Zafar ◽

Raza M Alvi ◽

Sean P Murphy ◽

...

Keyword(s):

Coronary Artery ◽

Autoimmune Disease ◽

Adverse Events ◽

Immune Checkpoint ◽

Cardiovascular Events ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Skin Toxicity ◽

Significant Difference

Introduction: The use of immune checkpoint inhibitors (ICIs) is associated with an increase in cardiovascular events. The mechanism is likely related to immune activation and inflammation. Patients with pre-existing autoimmune disease have a baseline increased risk for cardiovascular disease and have been traditionally excluded from clinical trials of ICIs. There is limited data on the cardiovascular and non-cardiovascular safety of ICIs in these patients. Methods: This was a retrospective study of 2845 patients treated with an ICI at the Massachusetts General Hospital. This cohort was screened by individual chart review for patients with a diagnosis of an autoimmune disease prior to ICI therapy. These autoimmune patients were compared to controls at a 1:2 ratio. Baseline characteristics and risk of cardiovascular and non-cardiovascular immune related adverse events (iRAEs) were compared. Cardiovascular events were a composite of myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), stroke, transient ischemic attack (TIA), deep venous thrombosis (DVT), pulmonary embolism (PE), or myocarditis. Results: 93 patients had a diagnosis of an autoimmune disease prior to ICI. These patients were more likely to be older and to have a history of coronary artery disease, heart failure, chronic kidney disease, hypertension and diabetes mellitus. There were 12 events over a median follow-up period of 300 days. There was no significant difference in composite of cardiovascular events in follow-up (13 vs. 9.1%, autoimmune vs. none, P =0.41). The individual cardiovascular event rates were as follows: MI (4.3 vs. 0.5%, P =0.04), PCI (0 vs. 0.5%, P =1), CABG (0. vs. 0.5%, P =1), stroke (0 vs. 0%), TIA (0 vs. 0.5%, P =1), DVT (5.4 vs. 2.2%, P =0.17), PE (1.1 vs. 4.8%, P =0.17), and myocarditis (2.2 vs. 1.1%, P =0.60). There was an increased rate of pneumonitis (14 vs. 4%, P <0.001) and skin toxicity (16 vs. 0%, P <0.001). Conclusions: Patients with pre-existing autoimmune disease treated with an ICI had a higher baseline cardiovascular risk but did not have a significant increase in cardiovascular events in an unadjusted analysis. These patients did, however, have an increased rate of pneumonitis and skin toxicity after ICI.

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Efficacy of immune checkpoint inhibitors for in-transit melanoma

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2019-000440 ◽

2020 ◽

Vol 8 (1) ◽

pp. e000440 ◽

Cited By ~ 1

Author(s):

Emilia Nan Tie ◽

Julia Lai-Kwon ◽

Michael Alexander Rtshiladze ◽

Lumine Na ◽

James Bozzi ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Single Agent ◽

Progression Free Survival ◽

Distant Metastases ◽

Mek Inhibitor ◽

Disease Recurrence ◽

In Transit

BackgroundThe efficacy of immune checkpoint inhibitors (ICI) in metastatic melanoma is well established. However, there are limited data regarding their efficacy in in-transit melanoma (ITM). This study assessed the efficacy of ICI in patients with ITM.MethodsA retrospective review of patients with ITM commenced on an ICI between March 2013 and February 2018 at three tertiary centers in Australia. Patients were excluded if they had previous or synchronous distant metastases. Overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were based on a composite of radiological and clinical assessments.ResultsFifty-four patients were included: 27 (50%) female; median age 75 (range 26–94); 12 (22%) stage IIIB, 40 (74%) stage IIIC and 2 (4%) stage IIID; 10 (19%) BRAF mutant. Forty (74%) received single-agent anti-PD-1 (pembrolizumab or nivolumab), 8 (15%) single agent anti-CTLA-4 (ipilimumab), 5 (9%) combination anti-PD-1/anti-CTLA-4 (ipilimumab and nivolumab or pembrolizumab) and 1 (2%) combination anti-PD-L1 (atezolizumab) and MEK inhibitor (cobimetinib). The median follow-up was 15 months (2–46).ORR to ICI was 54%: 14 (26%) complete responses; 15 (28%) partial responses; 9 (17%) stable disease; 16 (30%) progressive disease. Thirteen (46%) responders had only one ITM lesion. ORR was 58% for single-agent anti-PD-1, 38% for single-agent anti-CTLA4 and 40% for anti-PD-1/anti-CTLA-4. The median PFS was 11.7 months (6.6-not reached). 1-year and 2-year PFS were 48% and 39%, respectively,. Fourteen progressed locoregionally and 11 progressed distantly. The median OS was not reached. 1-year and 2-year OS were 85% and 63%, respectively. No clinicopathological features were associated with ORR.Conclusions and relevanceICI produce objective responses in ITM and should be considered in patients with unresectable ITM or disease recurrence.

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Efficacy of first-line immune checkpoint inhibitors in patients with sarcomatoid and/or rhabdoid (S/R) metastatic renal cell carcinoma (mRCC).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.8_suppl.66 ◽

2019 ◽

Vol 37 (8_suppl) ◽

pp. 66-66

Author(s):

Ziad Bakouny ◽

Sarah Abou Alaiwi ◽

Amin Nassar ◽

John A. Steinharter ◽

Xiao X. Wei ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Objective Response ◽

Multivariable Analysis ◽

Progression Free Survival ◽

First Line ◽

Free Survival ◽

Logistic Regressions

66 Background: Patients with mRCC with S/R components tend to have a poor prognosis with few therapeutic options available. Recent data suggest that immune checkpoint inhibitor (ICI)-based therapies may be especially effective for these patients. Our aim was to evaluate the efficacy of ICI-based therapies in patients with S/R mRCC. Methods: We retrospectively assessed objective response rate (ORR), progression free survival (PFS) & overall survival (OS) of patients with S/R mRCC treated at our institution with first-line ICI-based therapies and compared these to those of patients treated with first-line non-ICI-based therapies. Univariable and multivariable (adjusted for IMDC group) Cox and logistic regressions were performed. Results: 92 patients (70 S, 9 R, and 13 S&R) patients were included, of which 74 with a clear-cell component. For all patients (regardless of therapy), 74 (80.4%) patients experienced a PFS event (progression or death) and 52 (56.5%) died at 25.3 months (m) median follow-up. Overall median PFS was 5.3 m (95% CI= 3.4–7.2) and 24 m OS rate was 39.5% (27.4–51.7). Out of 78 patients in whom response was evaluable, ORR was 30.8% (20.4–41.2). Patients treated with ICI-based therapies had significantly better ORR, PFS, and OS on multivariable analysis (table). Conclusions: mRCC patients with S/R components have significantly better ORR, PFS, and OS with first-line ICI-based compared to non-ICI-based therapies. These data support the use of ICI-based therapies for patients with S/R mRCC. [Table: see text]

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