Remission Assessment by Circulating Tumor DNA in Large B-cell Lymphoma.

Purpose: Large B-cell lymphomas (LBCL) are curable, but patients with residual disease after therapy invariably experience progression. Ultrasensitive methods to detect circulating tumor DNA (ctDNA) as minimal measurable residual disease (MRD) may improve the determination of remission.

Methods: We integrated data from five prospective studies of frontline anthracycline-based chemotherapy in patients with LBCL.

A phase 1 study of interleukin-15 in combination with mogamulizumab in relapsed and refractory T-cell malignancies.

Recombinant human interleukin-15 (rhIL-15) is an immunotherapeutic agent that enhances natural killer (NK) cells to augment the antibody-dependent cellular cytotoxicity (ADCC) of monoclonal antibodies. Mogamulizumab is a CC chemokine receptor 4-directed monoclonal antibody that exerts cytotoxicity through ADCC and depletes regulatory T cells within the tumor microenvironment. We conducted a phase 1 clinical trial of rhIL-15 in combination with mogamulizumab.

The anti-CD47 antibody magrolimab with obinutuzumab and venetoclax in relapsed or refractory indolent B-cell lymphomas.

Follicular lymphoma (FL), marginal zone lymphoma (MZL), chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL) are characterized by a continuous incidence of relapse and increasing resistance to therapy. Novel immunotherapy approaches are needed. Magrolimab, a CD47-blocking antibody, disrupts CD47:SIRPα-mediated antiphagocytic signalling.

Acute Transient Aminotransferase Elevation is Common With Intrathecal Methotrexate, but Liver Injury is Infrequent.

Background And Aims: Hepatotoxicity is a known risk of oral and intravenous methotrexate (MTX), but whether intrathecal (IT) administration causes hepatotoxicity remains unknown. We aimed to explore whether IT-MTX causes acute hepatoxicity.

Methods: Retrospective single-centre analysis of all patients treated with IT-MTX from 2000 to 2020.

Circulating Tumor DNA as Measurable Residual Disease in Aggressive B-Cell Lymphoma: A Narrative Review.

Importance: Achieving remission is the first step toward a cure in treating aggressive B-cell lymphomas. Radiographic imaging, such as fluorodeoxyglucose-positron emission tomography/computed tomography scans are the current standard to define remission at the end of therapy but lack specificity for lymphoma and cannot detect disease at the molecular level. Identifying measurable residual disease with ultrasensitive detection of circulating tumor DNA potentially offers the possibility of improving clinical outcomes.

Phase 2 study of alemtuzumab and dose-adjusted EPOCH-R in relapsed or refractory aggressive B-cell lymphomas.

Immune cells within the lymphoma tumor microenvironment promote immune evasion and are rational therapeutic targets. Alemtuzumab targets CD52 expressed on malignant B-cells and infiltrating nonmalignant T-cells. We evaluated the safety and efficacy of alemtuzumab with DA-EPOCH-R in 48 patients with relapsed/refractory aggressive B-cell lymphoma.

Combination Targeted Therapy in Relapsed Diffuse Large B-Cell Lymphoma.

Background: The identification of oncogenic mutations in diffuse large B-cell lymphoma (DLBCL) has led to the development of drugs that target essential survival pathways, but whether targeting multiple survival pathways may be curative in DLBCL is unknown.

Methods: We performed a single-center, phase 1b-2 study of a regimen of venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR) in relapsed or refractory DLBCL. In phase 1b, which included patients with DLBCL and indolent lymphomas, four dose levels of venetoclax were evaluated to identify the recommended phase 2 dose, with fixed doses of the other four drugs.

BTK drives neutrophil activation for sterilizing antifungal immunity.

We describe a previously unappreciated role for Bruton's tyrosine kinase (BTK) in fungal immune surveillance against aspergillosis, an unforeseen complication of BTK inhibitors (BTKi) used for treating B cell lymphoid malignancies. We studied BTK-dependent fungal responses in neutrophils from diverse populations, including healthy donors, patients who were treated with BTKi, and X-linked agammaglobulinemia patients. Upon fungal exposure, BTK was activated in human neutrophils in a TLR2-, Dectin-1-, and FcγR-dependent manner, triggering the oxidative burst.

Primary large B-cell lymphomas of immune-privileged sites.

Diffuse large B-cell lymphoma (DLBCL) encompasses a diverse spectrum of aggressive B-cell lymphomas with remarkable genetic heterogeneity and myriad clinical presentations. Multiplatform genomic analyses of DLBCL have identified oncogenic drivers within genetic subtypes that allow for pathologic subclassification of tumors into discrete entities with shared immunophenotypic, genetic, and clinical features. Robust classification of lymphoid tumors establishes a foundation for precision medicine and enables the identification of novel therapeutic vulnerabilities within biologically homogeneous entities.

The follicular lymphoma tumor microenvironment at single-cell and spatial resolution.

Follicular lymphoma (FL) is a generally incurable malignancy that originates from developmentally blocked germinal center B cells residing, primarily, within lymph nodes (LNs). During the long natural history of FL, malignant B cells often disseminate to multiple LNs and can affect virtually any organ. Nonmalignant LNs are highly organized structures distributed throughout the body, in which they perform functions critical for host defense.

Clinical applications of circulating tumor DNA in indolent B-cell lymphomas.

Indolent B-cell lymphomas are generally incurable with standard therapy and most patients have a prolonged disease course that includes multiple treatments and periods of time in which they do not require therapy. Currently available tools to monitor disease burden and define response to treatment rely heavily on imaging scans that lack tumor specificity are unable to detect disease at the molecular level. Circulating tumor DNA (ctDNA) is a versatile and promising biomarker being developed across multiple lymphoma subtypes.

Phase I Study of Acalabrutinib Plus Danvatirsen (AZD9150) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma Including Circulating Tumor DNA Biomarker Assessment.

Purpose: Novel targeted and immunotherapies have improved outcomes in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but toxicities limit widespread use. The selective Bruton tyrosine kinase (BTK) inhibitor acalabrutinib has activity in patients with R/R DLBCL but durable responses are uncommon. STAT3 inhibition has demonstrated clinical activity in DLBCL.

Interferon alfa-2b in patients with low-grade lymphomatoid granulomatosis and chemotherapy with DA-EPOCH-R in patients with high-grade lymphomatoid granulomatosis: an open-label, single-centre, phase 2 trial.

Background: Lymphomatoid granulomatosis is a rare Epstein-Barr virus-associated B-cell lymphoproliferative disorder with a median overall survival of less than 2 years. In this study, we hypothesised that low-grade lymphomatoid granulomatosis is immune-dependent and high-grade lymphomatoid granulomatosis is immune-independent. On the basis of this hypothesis, we investigated the activity and safety of new treatment with immunotherapy in patients with low-grade disease and standard chemotherapy in patients with high-grade disease.

Role of Artificial Intelligence in PET/CT Imaging for Management of Lymphoma.

Our review shows that AI-based analysis of lymphoma whole-body FDG-PET/CT can inform all phases of clinical management including staging, prognostication, treatment planning, and treatment response evaluation. We highlight advancements in the role of neural networks for performing automated image segmentation to calculate PET-based imaging biomarkers such as the total metabolic tumor volume (TMTV). AI-based image segmentation methods are at levels where they can be semi-automatically implemented with minimal human inputs and nearing the level of a second-opinion radiologist.

Burkitt lymphoma.

Burkitt lymphoma (BL) is an aggressive form of B cell lymphoma that can affect children and adults. The study of BL led to the identification of the first recurrent chromosomal aberration in lymphoma, t(8;14)(q24;q32), and subsequent discovery of the central role of MYC and Epstein-Barr virus (EBV) in tumorigenesis. Most patients with BL are cured with chemotherapy but those with relapsed or refractory disease usually die of lymphoma.