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Introduction:Immunotherapy is less active in non-Hodgkin lymphoma due to immune evasion from the tumor microenvironment. For diffuse large B cell lymphoma (DLBCL), the overall response rates (ORR) for immune checkpoint inhibitors (ICIs) were low (4-18%). Bispecific antibodies (BiAb), such as FDA-approved Epcoritamab and Glofitamab, had a complete response (CR) rate of 39% for DLBCL. Methods that alter local and systemic immune microenvironments are needed to improve the response to immunotherapy. Unlike radiation, photothermal therapy (PTT) can generate a strong T-cell activation signal. PTT is created by irradiating specially designed gold nanoparticles with near-infrared (NIR) light. The nanoparticles absorb the light and transfer the energy into heat, leading to very localized ablations. The local high heat stimulates a cascade of pro-inflammatory cytokines, including IL-6, IL-1β, TNF-α, G-CSF, GM-CSF, and CCL2. We previously found that PTT with toll-like receptor 9 agonists had a significantly higher CD8 to CD4 ratio, cytotoxic T cell to regulatory T cell ratio, and effector memory T cells in a murine lymphoma model. The AuroLase system, which uses silica gold nanoshells and an FDA-cleared laser, has been undergoing clinical trials for various solid tumors. Here, we explore the systemic immune effects of the PTT device in a lymphoma murine model and evaluate its synergistic effects with ICIs and BiAbs.

Introduction:Systemic mastocytosis (SM) is a rare, clonal, hematopoietic neoplasm characterized by excessive proliferation and hyperactivation of abnormal mast cells (MCs). Approximately 95% of patients with SM harbor the KITD816V mutation within the KIT receptor tyrosine kinase, which results in constitutive activation of the KIT receptor. Abnormal activation of KIT leads to increased proliferation, survival, and hyperactivation of MCs, which can cause debilitating constitutional symptoms such as pruritus, flushing, headaches, bone pain, nausea, vomiting, diarrhea, and life-threatening anaphylaxis, across all SM subtypes.Polymerase chain reaction (PCR)-based detectionof the KITD816V mutation in bone marrow (BM) aspirates or other extracutaneous tissues is an important tool to confirm clinical and pathological diagnosis. In addition, genomic determination of the KITD816V variant allelic fraction (VAF) in peripheral blood (PB) or BM can serve as a potential prognostic tool and may also be used to monitor treatment efficacy over time. However, low numbers of neoplastic MCs in BM or PB samples, especially from patients with non-advanced forms of the disease (ISM and smoldering SM) can result in misdiagnosis and underestimation of disease burden. Here, we report on the performance of an adapted ddPCR assay compared with NGS for measuring the KITD816V VAF in PB samples from patients with moderate to severe ISM and symptoms inadequately controlled with best supportive care enrolled in part 1 (randomized dose finding part to determine recommended dose) of the ongoing, randomized, double-blind, placebo-controlled phase 2 PIONEER clinical study (NCT03731260) of avapritinib, a potent and selective inhibitor of KIT D816V mutant kinases.