Immunotherapy最新文献

Seasonal allergic rhinitis (SAR) is a chronic inflammatory condition primarily mediated by type 2 immune responses, typically triggered by specific pollens. Stapokibart is a humanized monoclonal antibody anti-interleukin-4 receptor α subunit, thereby blocking IL-4 and IL-13 signaling pathways. Clinical studies of stapokibart in healthy adults and SAR patients revealed a favorable safety profile and significant clinical efficacy. Stapokibart has been approved for treating adults with atopic dermatitis, chronic rhinosinusitis with nasal polyposis, and SAR in China. This article reviews the mechanism of action, pharmacology, and available clinical trial data regarding the efficacy and safety of stapokibart in SAR.

Purpose: To investigate real-world treatment patterns, incidence of immune-related adverse events (irAE), and impact of irAEs on outcomes in MBM.

Methods: We performed a retrospective study on MBM patients treated with immunotherapy in 2011-2022.

Results: Of the 1979 patients treated with immunotherapy, 453 had melanoma and 138 developed MBM. Median time from melanoma diagnosis to CNS metastasis was 37.8 months and median CNS PFS was 11.1 months. Higher burden of MBMs (6-10 or 11+) was associated with worse CNS PFS compared with low MBM burden (1-5 lesions) (HR = 1.89, 95% CI [1.10-3.25]; p = 0.022), (HR = 1.92, 95% CI [1.02-3.63]; p = 0.044). Synchronous MBM (within 30 days of stage IV diagnosis) was associated with improved CNS PFS (HR = 0.65, 95% CI [0.43-0.99]; p = 0.046). Median OS was 22.3 months from development of MBM and 35.0 months from date of first-line therapy for advanced melanoma. All patients received ICI and most (60.1%) developed any grade irAE. Patients who received combination ICI had higher rates of irAE than patients who received single-agent ICI (χ² = 16.31, p < 0.001). Development of irAE was associated with improved median OS (45.0 months vs 21.7 months, HR = 0.50, 95% CI [0.30-0.83]; p = 0.008).

Conclusion: Incidence of irAE was associated with improved survival and trended toward improved CNS PFS.

Hepatocellular carcinoma (HCC) often presents at an advanced stage, limiting treatment options. Historically, systemic therapies like tyrosine kinase inhibitors and VEGF-targeted antibodies offered modest survival benefits. HCC's immunosuppressive microenvironment, driven by regulatory T cells, myeloid-derived suppressor cells, and immune checkpoint signaling, hinders effective therapy. Immune checkpoint inhibitors (ICPIs) have revolutionized HCC management by targeting these pathways. Atezolizumab and bevacizumab (Atezo/Bev) is the standard first-line therapy for unresectable HCC, but post-progression options are limited. We explore the potential of switching to durvalumab and tremelimumab (Durva/Treme) as a second-line strategy. Recently approved, Durva/Treme shows promise, yet data on sequential ICPI use remain scarce. This editorial highlights the rationale for this approach, leveraging distinct immune targets to overcome resistance. Preliminary evidence suggests durable responses are achievable, but robust clinical trials are needed to validate efficacy, optimize sequencing, and identify biomarkers. Durva/Treme's role as a second-line option could address the critical gap in HCC treatment, challenging the immunosuppressive tumor microenvironment. We advocate for bold innovation to improve outcomes in this complex disease, urging further research into ICPI rechallenge strategies to transform the therapeutic landscape for patients with unresectable HCC.

Introduction: Pembrolizumab is a standard first-line therapy for advanced/metastatic non-small cell lung cancer (a/mNSCLC) lacking actionable mutations. Data from lower-middle-income countries (LMICs) remain scarce.

Methods: From January 2019 to June 2024, we prospectively analyzed 78 a/mNSCLC patients receiving pembrolizumab-based first-line therapy. Endpoints included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and conditional survival probabilities.

Results: With a median follow-up of 27 months, median OS was 21 months (95% CI: 12.2-30.8) and median PFS 6.3 months (95% CI: 5.5-10.1). At first response evaluation (2 months), partial response was seen in 47.4% (37/78), stable disease in 16.7% (13/78). Next-generation sequencing (85% tested) revealed non-actionable mutations in 70%; notably, 4 of 6 long-term survivors harbored KRAS mutations. PD-L1 TPS ≥ 50% significantly lowered progression and mortality risk. Age, performance status (ECOG), and disease response significantly influenced the OS. The conditional survival probability for an additional 6 months after surviving the first 6 months was 78.1% (90% in patients with controlled disease).

Conclusion: Real-world LMIC data demonstrated comparable effectiveness of pembrolizumab-based therapy in a/mNSCLC despite a higher proportion of adverse prognostic factors. More studies in diverse clinical settings are needed to provide a reliable estimate of benefit.

We report on the use of a daratumumab-CHOP regimen for treatment of gamma heavy chain disease (γHCD) in a 79-year-old woman. γHCD is a very rare hematological disease, often associated with an underlying lymphoproliferative disorder. Only a few cases are reported in the literature, and, therefore, strong evidence is lacking regarding new therapeutic strategies. We attempted a treatment with a monoclonal anti-CD38 antibody in association with conventional chemothorapy, due to CD38 expression by clonal cells. This is the first reported case in the literature, in a disease in which very few novel strategies have recently emerged.

Currently, the first-line treatment of non-metastatic Merkel cell carcinoma (MCC) is complete resection. In case of unresectable or metastatic MCC, immune checkpoint inhibitor (ICI) therapy with avelumab (or in the US also pembrolizumab or retifanlimab) is indicated. We report on a patient with a primary, non-metastatic MCC on the left eyelid and amyotrophic lateral sclerosis (ALS). Due to ALS, the patient's communication was limited to eye movement and blinking. Complete resection or definitive radiotherapy of the tumor while preserving the function of the eye muscles was not possible. No prior data was available for patients with ALS under ICI therapy. In agreement with the patient and his family, a monotherapy with avelumab, a programmed death ligand 1 (PD-L1) inhibitor, was initiated. This led to a complete remission of the tumor with a progression-free survival of over 24 months and importantly no deterioration of the ALS.