Myocardial Vasculitis Associated With the Immune Checkpoint Inhibitor Pembrolizumab.
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ABSTRACT:
SUBMITTER: Oishi H
PROVIDER: S-EPMC8299122 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Commentary on « Ipilimumab induced vasculitis » by Padda A. et al., J Immunother Cancer. 2018;6:12. The authors diagnosed a small vessel vasculitis following treatment with anti-CTLA-4 (ipilimumab) for a resected stage III B/C melanoma. We report a similar case of acral vasculitis occurring with a combination of anti-CTLA-4 (tremelimumab) and anti-PD-L1 (durvalumab) prescribed for the management of a metastatic urothelial bladder cancer. In contrast to Padda A. et al., we observed a significant improvement with oral corticosteroids.
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Project description:This is a case report of a 67-year-old patient with castration resistant metastatic prostate cancer who developed an immune-mediated large vessel vasculitis following treatment with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1).
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Project description:Side effects of immune checkpoint inhibitors, termed immune-related adverse events, are relatively common, but immune checkpoint inhibitor-mediated cardiotoxicities are rare; however, they can be serious and potentially fatal. Pericarditis is an infrequent cardiac toxicity of immunotherapy and predisposing factors remain unknown. Here we report three patients with NSCLC who developed pericarditis during therapy with programmed death 1/programmed death ligand 1+/- CTLA-4 inhibitors. We review the clinical presentation of these three cases and histopathologic findings from autopsies from the first two patients and a pericardial sampling that has been obtained from a pericardial window procedure in the third patient who recovered from the pericarditis episode. We also discuss the potential mechanisms, as well as what is known about pericarditis secondary to immune-related adverse events.
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Project description:Chordoma is a rare primary bone tumor that exhibits insensitivity to radiotherapy and chemotherapy and has a poor prognosis. Currently, resection is the primary treatment for affected patients, but the subsequent rate of recurrence is high, and both overall survival (OS) and progression-free survival (PFS) are consequentially relatively short. This case report describes a patient who was diagnosed with metastatic chordoma that was found to possess the A1209fs mutation of the PBRM1 gene, which may be associated with beneficial responses to immunotherapies. The patient received pembrolizumab, an immune checkpoint inhibitor (ICI) that targets the PD-1 receptor of lymphocytes, as second-line therapy, which he tolerated well (the most frequent adverse events were abnormal liver function and hyperglycemia, both of which were only grades 1-2), and achieved a PFS duration of 9.3 months. We hope these results will promote further research that will clarify the mechanisms underlying this beneficial response and that will further explore the use of immunotherapies in this population.
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Project description:BackgroundMyocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited.ObjectivesThis study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis.MethodsIn this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block.ResultsOf 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction <55%. Across all patients, mean z-scores for T1 and T2 values were 2.9 ± 1.9 (p < 0.001) and 2.2 ± 2.1 (p < 0.001), respectively. On Siemens 1.5-T scanner (n = 67), native T1 (1,079.0 ± 55.5 ms vs. 1,000.3 ± 22.1 ms; p < 0.001) and T2 (56.2 ± 4.9 ms vs. 49.8 ± 2.2 ms; p < 0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91 (95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p = 0.004) but not T2 values were independently associated with subsequent MACE.ConclusionsThe use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis.
| S-EPMC8442989 | biostudies-literature
Project description: Not available
| S-EPMC10088759 | biostudies-literature
Project description:BackgroundThe objective of this study was to characterize the clinicopathologic features of sicca syndrome associated with immune checkpoint inhibitor (ICI) therapy.Subjects, materials, and methodsConsecutive patients with new or worsening xerostomia in the setting of ICI treatment for benign or malignant neoplastic disease were evaluated, including labial salivary gland biopsy (LSGB).ResultsTwenty patients (14 male; median age 57 years) had metastatic melanoma (n = 10), metastatic carcinoma (n = 6), or recurrent respiratory papillomatosis (n = 4) and were being treated with avelumab (n = 8), nivolumab (n = 5), pembrolizumab (n = 4), nivolumab/ipilimumab (n = 2), and M7824, a biologic targeting programmed cell death ligand 1 (PD-L1) and transforming growth factor ß (n = 1). Four had pre-existing autoimmune disease. Nineteen had very low whole unstimulated saliva flow; six had new dry eye symptoms. The median interval between ICI initiation and dry mouth onset was 70 days. Rheumatoid factor and anti-Sjögren's Syndrome-related Antigen A (Anti-SSA) were both positive in two subjects. LSGB showed mild-to-severe sialadenitis with diffuse lymphocytic infiltration and architectural distortion. There were lymphocytic aggregates in eight patients, composed mainly of CD3+ T cells with a slight predominance of CD4+ over CD8+ T cells. ICI targets (e.g., programmed cell death 1 and PD-L1) were variably positive. In direct response to the advent of the sicca immune-related adverse event, the ICI was held in 12 patients and corticosteroids were initiated in 10. Subjective improvement in symptoms was achieved in the majority; however, salivary secretion remained very low.ConclusionICI therapy is associated with an autoimmune-induced sicca syndrome distinct from Sjögren's syndrome, often abrupt in onset, usually developing within the first 3 months of treatment, and associated with sialadenitis and glandular injury. Improvement can be achieved with a graded approach depending on severity, including withholding the ICI and initiating corticosteroids. However, profound salivary flow deficits may be long term.Implications for practiceSicca syndrome has been reported as an immune-related adverse event (irAE) of immune checkpoint inhibitor therapy (ICI) for neoplastic diseases. Severe dry mouth (interfering with eating or sleeping) developed abruptly, typically within 90 days, after initiation of ICI therapy. Salivary gland biopsies demonstrated mild-to-severe sialadenitis distinct from Sjögren's syndrome, with diffuse T-cell lymphocytic infiltration and acinar injury. Recognition of the cardinal features of ICI-induced sicca will spur appropriate clinical evaluation and management, including withholding of the ICI and corticosteroid, initiation. This characterization should help oncologists, rheumatologists, and oral medicine specialists better identify patients that develop ICI-induced sicca to initiate appropriate clinical evaluation and therapy to reduce the likelihood of permanent salivary gland dysfunction.
| S-EPMC6738284 | biostudies-literature
Project description:We evaluated the efficacy and safety of TAS0313, a multi-epitope long peptide vaccine, plus pembrolizumab in post-chemotherapy immune checkpoint inhibitor-naïve patients with locally advanced/metastatic urothelial carcinoma (la/mUC). TAS0313 9 mg was administered subcutaneously followed by pembrolizumab 200 mg on Day 1, and as monotherapy on Day 8 and 15 of Cycles 1 and 2, and Day 1 of subsequent cycles in 21-day cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Biomarkers of response were assessed. In 36 patients enrolled, the ORR was 33.3% (complete response: 7 patients; partial response: 5 patients). Median PFS was 5.0 months; 6- and 12-month progression-free rates were 46.4% and 36.5%, respectively. Median OS was not reached; 6-, 12-, and 24-month OS rates were 83.3%, 72.2%, and 55.1%, respectively. In post hoc analysis, patients with a tumor infiltrating CD8+ lymphocyte (CD8+ TIL) count ≥99 and/or programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥50 and lymphocyte count >1,380 cells/μL had higher ORRs and prolonged PFS versus patients with a CD8+ TIL count <99, PD-L1 CPS <50, and lymphocyte count ≤1,380 cells/μL. Thirty-four (94.4%) patients receiving combination therapy experienced treatment-related adverse events (AE), with pyrexia (n = 15, 41.7%), injection-site reactions (n = 15, 41.7%), injection-site induration (n = 6, 16.7%), and malaise (n = 6, 16.7%) the most common. No grade ≥3 treatment-related AEs occurred in ≥10% of patients. TAS0313 plus pembrolizumab combination therapy showed promising efficacy and manageable safety in la/mUC. Clinical Trial Registration: JapicCTI-183824.
| S-EPMC10985476 | biostudies-literature
Project description:BackgroundImmune checkpoint inhibitors (ICIs) are highly effective in treating cancer; however, cardiotoxicity can occur, including myocarditis. Cardiac magnetic resonance (CMR) imaging is useful for evaluation of myocarditis, although it has not been well studied in ICI cardiotoxicity.MethodsWe identified patients referred for CMR evaluation of ICI cardiotoxicity from September 2015 through September 2019. We assessed structural and functional parameters, feature tracking (FT) left ventricular and atrial strain, T2- weighted ratios and quantitative late gadolinium enhancement (LGE). We also applied the Updated Lake Louise Criteria for diagnosis of myocarditis.ResultsOf the 20 patients referred, the median left ventricular ejection fraction (LVEF) was 52.5% ± 19.1 and 50% had a normal LVEF (≥53%). FT strain analysis revealed an average abnormal global longitudinal strain (GLS) of -9.8%± 4.2%. In patients with a normal LVEF, the average GLS remained depressed at -12.3%± 2.4%. In all patients, GLS demonstrated a significant negative correlation with LVEF (rs = -0.64, p 0.002). Sixteen patients (80%) had presence of LGE (14 non-ischemic pattern and 2 ischemic). Percent LGE did not correlate with any CMR parameters and notably did not correlate with LVEF (rs = -0.29, p = 0.22) or GLS (rs = 0.10, p = 0.67), highlighting the value of tissue characterization beyond functional assessment. Nine patients (45%) met full Updated Lake Louise Criteria and 85% met at least one criterion, suggestive of myocarditis in the correct clinical context. Thirteen patients (65%) were treated for ICI-associated myocarditis and, of these, 54% (n = 7) had recovery of LVEF to normal. There was no correlation between LVEF (p = 0.47), GLS (0.89), or % LGE (0.15) and recovery of LVEF with treatment.ConclusionIn patients with suspected ICI cardiotoxicity, CMR is an important diagnostic tool, even in the absence of overt left ventricular dysfunction, as abnormalities in left ventricular strain, T2 signal and LGE can identifying disease.
| S-EPMC7895343 | biostudies-literature