Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired, rare, life-threatening hematopoietic stem cell disorder that causes stem cell-derived cells to be vulnerable to complement-mediated lysis and manifests as hemolytic anemia, thrombosis, and peripheral blood cytopenias. C5 inhibitors, eculizumab, and ravulizumab, are recognized as the current standard of care for PNH treatment in countries where they are available. Crovalimab (PiaSky®), which is approved for the treatment of PNH, is a novel anti-C5 inhibitor with an every-4-weeks, low-volume, subcutaneous maintenance dosing regimen with the possibility for self-administration. Data from three phase III studies highlight the overall favorable benefit-risk profile of crovalimab, showing that crovalimab has promising potential to address the unmet medical and socioeconomic challenges in the PNH treatment landscape.

Immune checkpoint inhibitors (ICIs) related myocarditis is a rare complication of modern immunotherapy. It can present as an asymptomatic subclinical condition or full-blown fulminant myocarditis with malignant arrythmias and cardiogenic shock. Myositis/rhabdomyolysis and/or myasthenic symptoms can be present concomitantly. We present a case of fatal fulminant myocarditis presenting with cardiac arrythmias and severe systolic dysfunction, with accompanying rhabdomyolysis after the first dose of ipilimumab and nivolumab immunotherapy. First working diagnosis of subacute late presenting acute myocardial infarction (ACS) was incorrect and the correct diagnosis was established only after additional testing and consultation. Treatment consisted of high-dose corticosteroids, intravenous immunoglobulins, sedation with mechanical ventilation, antibiotic coverage, hemodialysis, and sustained low-efficiency daily diafiltration (SLEDD) with CytoSorb or TheraNova membranes, and intra-aortic balloon pump mechanical cardiac support. No tangible improvement in the condition was observed during the whole treatment period and the patient died on the sixth day of intensive care treatment.

Patients with moderate-to-severe rheumatoid arthritis (RA) in China experience multi-system dysfunction, resulting in a substantial economic burden. This study aimed to compare the cost-effectiveness of Upadacitinib and Tofacitinib as treatment options for moderate-to-severe RA patients in China.

Circulating tumor DNA (ctDNA) represents a powerful measure of minimal residual disease (MRD) in colorectal cancer (CRC). Although immunotherapy has been widely established in metastatic CRC that is mismatch repair deficient or microsatellite instability-high (dMMR/MSI-H), its role in non-metastatic CRC is rapidly evolving. In resected, dMMR/MSI-H stage II CRC, adjuvant fluoropyrimidine has no benefit and is not recommended. There is growing evidence to suggest diminished benefit from neoadjuvant chemotherapy and chemoradiation in localized CRC that is dMMR/MSI-H. We present two cases of dMMR/MSI-H stage III CRC treated with definitive surgery wherein adjuvant oxaliplatin-based chemotherapy led to a failure to clear postoperative plasma ctDNA levels, prompting a change to immune checkpoint blockade with pembrolizumab and resultant ctDNA clearance. We illustrate that chemotherapy may achieve suboptimal disease control in localized colon cancer that is dMMR/MSI-H, while plasma ctDNA offers a window of opportunity to gauge the efficacy of oxaliplatin-based adjuvant chemotherapy to clear microscopic disease in resected, dMMR/MSI-H stage III colon cancer. These findings are important to contextualize given that relapse is inevitable with failure to clear MRD in the postoperative stage I-III CRC setting whereby chemotherapy remains the standard adjuvant therapy in resected, dMMR/MSI-H stage III colon cancer.

Cytokine release syndrome (CRS) is an uncommon but deadly side effect of immune checkpoint inhibitors (ICIs). ICIs are presently an increasingly important therapy option for malignant tumors, but there are limited treatments available for CRS. We present a case of a 72-year-old man who received one cycle of ICI coupled with cisplatin and albumin-binding paclitaxel therapy for a locally advanced right lung adenocarcinoma. Following an abrupt onset of dyspnea, the patient underwent a quick physical examination, blood tests and was diagnosed with CRS. After prompt initiation of glucocorticoid pulse treatment, the symptoms relieved. The case illustrates the management of severe CRS following ICI therapy while highlighting the uncommon and potentially fatal immune-related side effects.

This study estimated avoided recurrences and treatment costs in patients with stage II-IIIA non-small cell lung cancer treated with adjuvant atezolizumab in five European countries over 10 years (2024-2034).

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, but they can induce immune-related adverse events, including immune checkpoint inhibitor-associated pneumonia (CIP), a severe lung complication. CIP, particularly Grades 3-4, is associated with poor prognosis, indicating a critical need for research on this issue. Our study aimed to investigate the risk factors and biomarkers associated with severe CIP in lung cancer patients treated with ICIs, where OS represents overall survival and PFS denotes progression-free survival.

This study evaluates the cost-effectiveness of tislelizumab plus chemotherapy as a first-line treatment for locally advanced or metastatic (IIIB/IV) nonsquamous non-small cell lung cancer (nsq-NSCLC) in China.

With the advent of chimeric antigen receptors T-cell therapy, understanding their role in the development of hemophagocytic lymphohistiocytosis has become increasingly complex. We describe a case of a young patient with Epstein-Barr virus-positive diffuse large B-cell lymphoma, who was treated with axicabtagene ciloleucel. The patient developed progressive cytopenia and, on Day 73 post-infusion, met criteria for hemophagocytic lymphohistiocytosis. Bone marrow evaluation revealed hemophagocytosis without evidence of clonal B cells. The patient was treated with tocilizumab, dexamethasone, etoposide and anakinra, which eventually led to improvement. Unfortunately, the patient succumbed to an infection. Disease progression was confirmed posthumously.This case report explores the differential diagnosis of hyperinflammatory syndromes following chimeric antigen receptor T-cell therapy and highlights the reduced efficacy of this treatment in patients with a T-cell/histiocyte-rich background.

Allergen immunotherapy is a disease-modifying treatment for allergic diseases. The predominant traditional immunotherapy is through subcutaneous administration of allergens to gradually desensitize allergic individuals. While effective, traditional allergen immunotherapy approaches are often lengthy, time consuming for patients and can result in local or systemic adverse reactions. Nontraditional immunotherapies are emerging as promising alternatives, offering potentially more convenient, safe and efficacious treatment options. This review sought to comprehensively examine the safety, efficacy and performance of various nontraditional immunotherapies for environmental allergens. Nontraditional immunotherapy approaches covered in this review include sublingual, local nasal, intralymphatic rush and ultra-rush immunotherapy, allergoid, microbial and anti-IgE immunotherapies. Nontraditional immunotherapies show significant promise in addressing the limitations of traditional subcutaneous immunotherapy. Methods like intralymphatic and rush immunotherapy offer shorter treatment regimens, enhancing patient adherence and convenience. The co-administration of probiotics or monoclonal antibodies, like omalizumab, with AIT appears to improve treatment efficacy and safety. Despite these advancements, further large-scale, long-term studies are needed to establish standardized protocols, dosing and validate long-term effects of these nontraditional immunotherapies. Standardizing outcome measurements across studies is crucial for accurate comparisons of nontraditional immunotherapies prior to widespread clinical adoption of these innovative techniques.

This summary outlines the findings from the ANANKE study on the treatment of patients with severe eosinophilic asthma (SEA) with benralizumab. SEA is an inflammatory disease of the lungs caused by eosinophils. Patients with SEA may experience asthma attacks (exacerbations) and decreased ability to breathe (lung function) despite taking medications. Benralizumab (Fasenra) is a biologic therapy (a medicine produced using living cells) approved for the treatment of SEA.The ANANKE study was conducted in Italy and evaluated the characteristics of patients with SEA who received benralizumab as prescribed by their doctors. It also described the effects of benralizumab on participants in terms of frequency of exacerbations, lung function and overall control of asthma, and their need to take oral corticosteroids (OCS) to control symptoms. The effects of benralizumab have been observed in participants treated for: 1) an average of 10.3 months, and 2) up to 96 weeks (approximately 2 years). The effects were also compared between different groups: 1) participants with chronic rhinosinusitis with nasal polyps (CRSwNP) and those without, and 2) participants who received other biologics before benralizumab (bio-experienced) and those who started with benralizumab as their first biologic (naïve). CRSwNP is an inflammatory condition that makes breathing even more difficult.

Hidradenitis suppurativa (HS) is a painful, inflammatory dermatosis involving recurrent abscesses, nodules and tunnels in intertriginous regions. Biologics and other immunomodulators have significantly expanded the treatment options available for HS. Bimekizumab is a monoclonal antibody targeting both interleukin-17A and interleukin-17F, key mediators of inflammation, that is already approved for psoriasis, psoriatic arthritis and axial spondylarthritis. It is currently pending FDA review for HS treatment but has already received marketing authorization for this indication in Europe. This review aims to explore drug-specific characteristics of bimekizumab including its mechanism of action, pharmacokinetics and pharmacodynamics and the current state of the literature regarding its use in HS such as safety, efficacy and dosing, while highlighting its implications in clinical practice. Recent Phase II and III trial data demonstrating positive efficacy and safety profiles in the treatment of HS will also be detailed.

Immunoglobulin G (IgG) therapies have been used for decades as standard treatment for patients with primary antibody deficiencies. Monitoring the pharmacokinetics (PK) of IgG is a key component in guiding treatment regimens. Despite the wealth of clinical experience, substantial gaps exist in our understanding of the true nature of IgGs and their disposition in humans. Furthermore, intrinsic and extrinsic factors may alter the PK of IgG, necessitating an individualized approach for patients. A comprehensive literature review was performed in order to summarize the PK of IgGs, examine the mechanisms of IgG disposition (including catabolism), outline considerations for special patient populations and discuss knowledge gaps and future perspectives for improving our understanding of IgG PK in relation to the individualized treatment paradigm.

Immunoglobulin G (IgG) dosing in treating primary immunodeficiency diseases (PIDs) is individualized, which often involves regular monitoring of IgG levels, and considers patient experiences with immunoglobulin therapies, their clinical status and physician judgment. The frequency and dose(s) of intravenously (IVIG) and subcutaneously (SCIG) administered IgGs (including hyaluronidase-facilitated SCIG) require rigorous evaluation to maximize therapeutic benefits. Monitoring serum IgG levels represents an integral part of diagnosing primary immunodeficiency diseases and determining or adjusting IgG dosing strategies to meet individual patient needs, but cannot be conducted in isolation. This review discusses the current state and future perspectives on dosing strategies for different types of IgG therapies, as well as dosing considerations for specific patient populations, immunoglobulin-naive patients and patients switching between IVIG and SCIG.

CD19 chimeric antigen receptor T (CAR-T) cell therapy represents an effective approach to treating patients with relapsed or refractory B-cell hematologic malignancies. Nevertheless, owing to the immunosuppressive effects of this regimen, patients undergoing CD19 CAR-T cell therapy may face an elevated risk of invasive fungal infections, which involve fungi penetrating the host's tissues or bloodstream, leading to life-threating infectious diseases. Herein, we present the case of a 17-year-old male diagnosed with acute lymphoblastic leukemia, who subsequently experienced a fatal invasive fungal infection following administration of CAR-T cell therapy. Furthermore, we delve into the identification of risk factors, implementation of preventive measures and exploration of therapeutic interventions for invasive fungal infections after CAR-T cell therapy.

Autologous chimeric antigen receptor (CAR)-modified T (CAR-T) cell therapy has displayed high efficacy in the treatment of hematological malignancies. Up to now, 11 autologous CAR-T cell products have been approved for the management of malignancies globally. However, the application of autologous CAR-T cell therapy has many individual limitations, long time-consuming, highly cost, and the risk of manufacturing failure. Indeed, some patients would not benefit from autologous CAR-T cell products because of rapid disease progression. Allogeneic CAR-T cells especially universal CAR-T (U-CAR-T) cell therapy are superior to these challenges of autologous CAR-T cells. In this review, we describe basic study and clinical trials of U-CAR-T cell therapeutic methods for malignancies. In addition, we summarize the problems encountered and potential solutions.

Immune-checkpoint inhibitors (ICIs) have revolutionized treatment of metastatic head and neck squamous cell carcinomas (HNSCCs). Our goal was to assess for an association between immune-related adverse events (irAEs) and clinical outcomes for patients on ICIs. We analyzed a cohort of 110 HNSCC patients who received ICI therapy at the University of Virginia. On review, 48% of our patients experienced an irAE with the most common events being hypothyroidism (30%), dermatitis (14%) and hepatitis (11%). Women were more likely to experience irAEs. Treatment interruption/discontinuation occurred in 43% patients with irAEs. Development of irAEs was associated with superior objective response rate (68 vs. 39%,  = 0.009), with a greater rate of CR (17 vs. 5%) and PR (32 vs. 16%). Twelve patients underwent ICI re-treatment following irAE, with 17% attaining a complete disease response, 25% attaining a partial response, 33% achieving stable disease and 25% experiencing disease progression with ICI resumption. Development of irAE was associated with superior objective response rate, with a greater rate of CR and PR. ICI re-treatment following irAE was feasible in a significant proportion of patients and can be attempted in carefully selected patients, given the dearth of second-line therapies for these patients.