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Aim: To evaluate adverse events in cancer patients with pre-existing sarcoidosis receiving immune checkpoint inhibitors (ICIs). Patients & methods: We retrospectively reviewed cancer patients with sarcoidosis who underwent treatment with ICI to determine frequency of sarcoidosis flares. Results: 32 patients with sarcoidosis received ICIs The median time to ICI initiation was 7 years (range: 1 month to 51 years). One patient (3%) with a 20-year remote history of sarcoidosis developed a clinically symptomatic exacerbation after three doses of atezolizumab, with hilar lymphadenopathy, subcutaneous nodules, arthritis and uveitis. Atezolizumab was discontinued and prednisone initiated. She had a fluctuating course with two additional flares. Conclusion: Frequency of flares in patients with a remote history of sarcoidosis who receive ICIs is low.

Objective: To describe an unusual immune-related adverse event (irAE), acquired generalized lipodystrophy (AGL), from checkpoint inhibitor therapy in a patient treated with pembrolizumab. Methods: This is a case report of a 67-year-old male with metastatic melanoma who was treated with pembrolizumab. Prior to pembrolizumab, the patient was treated with another immune-checkpoint inhibitor and developed autoimmune hemolytic anemia. After starting pembrolizumab, he developed a scrotal mass consistent with panniculitis and after several subsequent cycles, he developed AGL. Results: Loss of subcutaneous fat, unexplained weight loss in combination with worsening insulin resistance and worsening hypertriglyceridemia after initiation of pembrolizumab were consistent with AGL. Autoimmune disorders and other etiologies were ruled out. Despite this irAE, the patient continued to receive pembrolizumab given stabilization of melanoma with treatment. Conclusion: We report the second case of a patient who developed AGL secondary to pembrolizumab, and the fourth case to report such complication secondary to antiprogrammed cell death receptor-1 inhibitors. As use of checkpoint inhibitors becomes more common to treat several types of cancer, it is vital for clinicians to recognize these rare irreversible complications that are not frequently reported in clinical trials.

With durable cancer responses, genetically modified cell therapies are being implemented in various cancers. However, these immune effector cell therapies can cause toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Pseudogout arthritis is an inflammatory arthritis induced by deposition of calcium pyrophosphate dihydrate crystals. Here, we report a case of pseudogout arthritis in a patient treated with MAGE-A4 directed T cell receptor T cells, for fallopian tube cancer. The patient developed CRS and ICANS 7 days after infusion of the T cells. Concurrently, the patient newly developed sudden onset of left knee arthritis. Synovial fluid analyses revealed the presence of calcium pyrophosphate dihydrate crystal. Notably, the pseudogout arthritis was resolved with tocilizumab, which was administered for the treatment of CRS and ICANS. Immunoprofiling of the synovial fluid showed that the proportion of inflammatory interleukin 17 (IL-17)-producing CD4+ T (Th17) cells and amount of IL-6 were notably increased, suggesting a potential role of Th17 cells in pseudogout arthritis after T-cell therapy. To the best of our knowledge, this is the first reported case of pseudogout arthritis after cell therapy. Clinicians, especially hematologists, oncologists and rheumatologists, should be aware that pseudogout arthritis can be associated with CRS/ICANS.

Patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) treated with immune checkpoint inhibitors (ICIs) are at risk of pneumonitis as well as pneumonia (combined henceforth as ICI-related pulmonary complications). Little is known about the cellular and molecular mechanisms underlying ICI-related pulmonary complications. We characterized lymphocytes from bronchoalveolar lavage (BAL) fluid and peripheral blood from seven AML/MDS patients with pulmonary symptoms after ICI-based therapy (ICI group) and four ICI-naïve AML/MDS patients with extracellular bacterial or fungal pneumonias (controls). BAL T cells in the ICI group were clonally expanded, and BAL IFNγ+ IL-17− CD8+ T and CXCR3+ CCR6+ Th17/Th1 cells were enriched in the ICI group. Our data suggest that these cells may play a critical role in the pathophysiology of ICI-related pulmonary complications. Understanding of these cell populations may also provide predictive and diagnostic biomarkers of ICI-related pulmonary complications, eventually enabling differentiation of pneumonitis from pneumonia in AML/MDS patients receiving ICI-based therapies.

Introduction Immune checkpoint inhibitors (ICIs) are often associated with inflammatory toxicities known as immune-related adverse events (irAEs). Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is an atypical inflammatory arthritis. Herein, we report a case of RS3PE in a patient with metastatic prostate cancer who was receiving a combination of second-generation hormonal therapies plus ipilimumab. Case Presentation A 59-year-old man with metastatic prostate cancer developed sudden onset of pain and swelling of the right hand after 15 weeks of treatment with second-generation hormonal therapies plus three cycles of ipilimumab. Symptoms alternated to the left hand. Physical examination showed tender, pitting edema of the left hand with tenderness on the right second through fifth metacarpal phalangeal joints, leading to the diagnosis of RS3PE. Ipilimumab was withheld, and the RS3PE self-resolved; however, 1 month later, the patient had another flare of RS3PE. A bone scan showed active inflammation on bilateral wrists and hands. Methotrexate was initiated, and his symptoms resolved over a few days. Methotrexate was discontinued 2 months later, and RS3PE has been in complete remission. His prostate cancer progressed, and radium-223 treatment was initiated. Conclusion To the best of our knowledge, this is the first reported case of RS3PE after the combined second-generation hormonal therapy plus ipilimumab. Both rheumatologists and oncologists should be aware that RS3PE can develop as an irAE. Understanding the mechanism of ICI therapy–associated RS3PE is critical to identify predictive biomarkers and develop optimal therapeutic strategies that do not sacrifice antitumor immunity.

Although cisplatin is very effective as a treatment strategy in triple-negative breast cancer (TNBC), it has unwarranted outcomes owing to recurrence, chemoresistance and neurotoxicity. There is critically important to find new, effective and safe therapeutics for TNBC. We determined if SP-receptor antagonism in combination with cisplatin may serve as a novel, more efficacious and safer therapeutic option than existing therapies for TNBC. We used a neuronal cell line (PC12) and two TNBC cell lines (Sum 185 and Sum 159) for these studies. We determined that the levels of cells expressing the high-affinity SP-receptor (neurokinin 1 receptor (NK1R)), as determined by flow-cytometry was significantly elevated in response to cisplatin in all three cells. We determined that treatment with aprepitant, an SP-receptor antagonist decreased cisplatin-induced, loss of viability (studied by MTT assay), production of reactive oxygen species (by DCFDA assay) and apoptosis (by flow-cytometry) in PC12 cells while it was increased in the two TNBC cells. Furthermore, we demonstrated that important genes associated with metastases, inflammation, chemoresistance and cell cycle progression are attenuated by SP-receptor antagonism in the TNBC cell line, Sum 185. These studies implicate that SP-receptor antagonism in combination with cisplatin may possibly serve as a novel, more efficacious and safer therapeutic option than existing therapies for TNBC.

Background Despite ground-breaking clinical success in the treatment of different cancers, immune checkpoint inhibitors can cause profound inflammatory and immune-related adverse events. Autoimmune inflammatory arthritis following immune checkpoint inhibitor treatment has been reported; however, to date, no cases of crystal arthritis following immune checkpoint inhibitors have been identified. Case presentation We report the first case of recurrent pseudogout, an inflammatory crystal arthritis, in a patient treated with nivolumab, a PD-1 inhibitor, for renal cell carcinoma. The patient had recurrent pseudogout flares about week to 10 days after each nivolumab infusion. After treatment with prophylactic colchicine, the patient well tolerated additional nivolumab infusions without adverse events. In parallel, we characterized immune cells of synovial fluid at each flare. Immunoprofiling of synovial fluid showed that the proportion of inflammatory IL-17-producing CD4+ T cells and amount of IL-17 were notably increased in synovial fluid with every recurrent flair, and correlated with the increase in number of synovial neutrophils, suggesting a potential role of T helper 17 (Th17) cells in neutrophil-driven inflammation during pseudogout arthritis. Conclusions This case suggests a potential influence of Th17 cells on the neutrophil recruitment and neutrophil-driven inflammatory events leading to pseudogout induced by immune checkpoint inhibitor therapy.