Small molecule protein assembly modulators with pan-cancer therapeutic efficacy.

Two structurally unrelated small molecule chemotypes, represented by compounds PAV-617 and PAV-951, with antiviral activity in cell culture against Mpox virus (formerly known as monkeypox virus) and human immunodeficiency virus (HIV) respectively, were studied for anti-cancer efficacy. Each exhibited apparent pan-cancer cytotoxicity with reasonable pharmacokinetics. Non-toxicity is demonstrated in a non-cancer cell line and in mice at doses achieving drug exposure at active concentrations.

Clinicopathologic features of primary central nervous system anaplastic large cell lymphoma: a multicenter study identifies age and ALK status as prognostic factors.

Anaplastic large cell lymphoma with primary presentation in, and disease limited to, the central nervous system (primary CNS ALCL) is a rare and aggressive lymphoma found in a sensitive anatomic site. We report the clinical and pathologic characteristics of 17 primary CNS ALCL cases that are newly reported from six academic medical centers. We are investigating the characteristics of these cases, alongside their commonalities and differences from systemic ALCL arising at conventional anatomic sites.

Utility of PD-1, PD-L1, and IDO-1 Stains in Ocular Extranodal Marginal Zone Lymphoma (MZL) and Diffuse Large B-cell Lymphoma (DLBCL).

Extranodal marginal zone lymphoma (EMZL) is the most common subtype of ocular lymphomas. Diffuse large B-cell lymphoma (DLBCL) and EMZL with large-cell transformation present diagnostic challenges. Radiotherapy is the standard treatment for ocular lymphomas, but complications and relapse are common.

Myeloablative vs nonmyeloablative consolidation for primary central nervous system lymphoma: results of Alliance 51101.

Although it is evident that standard-dose whole-brain radiotherapy as consolidation is associated with significant neurotoxicity, the optimal consolidative strategy for primary central nervous system lymphoma (PCNSL) is not defined. We performed a randomized phase 2 clinical trial via the US Alliance cancer cooperative group to compare myeloablative consolidation supported by autologous stem cell transplantation with nonmyeloablative consolidation after induction therapy for PCNSL. To our knowledge, this is the first randomized trial to be initiated that eliminates whole-brain radiotherapy as a consolidative approach in newly diagnosed PCNSL.

Liquid biopsy for improving diagnosis and monitoring of CNS lymphomas: A RANO review.

Background: The utility of liquid biopsies is well documented in several extracranial and intracranial (brain/leptomeningeal metastases, gliomas) tumors.

Methods: The RANO (Response Assessment in Neuro-Oncology) group has set up a multidisciplinary Task Force to critically review the role of blood and cerebrospinal fluid (CSF)-liquid biopsy in CNS lymphomas, with a main focus on primary central nervous system lymphomas (PCNSL).

Results: Several clinical applications are suggested: diagnosis of PCNSL in critical settings (elderly or frail patients, deep locations, and steroid responsiveness), definition of minimal residual disease, early indication of tumor response or relapse following treatments, and prediction of outcome.

Older patients with primary central nervous system lymphoma: Survival and prognostication across 20 U.S. cancer centers.

There is a paucity of large-scale data delineating outcomes and prognostication of older patients with primary central nervous system lymphoma (PCNSL). We retrospectively analyzed 539 newly-diagnosed PCNSL patients ages ≥60 years across 20 U.S.

EBV-positive PCNSL in older patients: incidence, characteristics, tumor pathology, and outcomes across a large multicenter cohort.

The objective of this multicenter retrospective study was to examine the incidence, patient characteristics, pathology, and outcomes associated with Epstein-Barr virus (EBV)-related CNS lymphoma (CNSL) in older patients. Among 309 CNSL patients aged ≥60, 11.7% had EBV + tumors of which 72.

Stereotactic Radiosurgery for Primary Central Nervous System Lymphoma.

Background Primary central nervous system lymphoma (PCNSL) is rare, with a treatment backbone that typically includes high-dose methotrexate-based chemotherapy, with radiation often reserved for persistent or progressive disease. In this study, we report the outcomes of stereotactic radiosurgery (SRS) in patients with PCNSL to potentially defer whole brain radiotherapy (WBRT) or as salvage after WBRT. Methodology We performed a single-institution, retrospective review of 20 patients with PCNSL who received single-fraction or fractionated SRS to 32 lesions between September 1992 and July 2019.

Primary CNS lymphoma: update on molecular pathogenesis and therapy.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of extra-nodal non-Hodgkin lymphoma that as a brain tumor poses a unique set of challenges in diagnosis and management. With the advent of next-generation sequencing, we review updates in the understanding of its molecular and genomic pathogenesis. We also highlight key issues in management, with a focus on emerging technologies and new biological therapies including monoclonal antibodies, IMiDs, BTK inhibitors, PD-1 inhibitors, and CAR-T therapy.

Primary CNS Lymphoma: Progress With Dose-Intensive Consolidation.

Journal Journal of Clinical Oncology

Acquired factor VII inhibitor associated with primary central nervous system Lymphoma: A case report.

Paraneoplastic coagulopathies are uncommon in patients with lymphoma. We report the first case of an acquired coagulopathy in a patient with isolated primary central nervous system lymphoma (PCNSL) demonstrating large-cell histology. In our patient, a paraneoplastic factor VII inhibitor significantly delayed a diagnostic lumbar puncture despite fresh frozen plasma and inactivated prothrombin complex concentrate.

Primary central nervous system lymphoma in older adults and the rationale for maintenance strategies: a narrative review.

Objective: To provide a summary and analysis of the evidence for various agents applied as maintenance therapy and highlight ongoing trials or trials in development that evaluate the efficacy of maintenance therapy strategies in older patients with primary central nervous system lymphoma (PCNSL).

Background: PCNSL are rare neoplasms that can have an aggressive course with short-lived remissions when compared to systemic diffuse large B-cell lymphoma (DLBCL). There is currently a paucity of evidence on treatment in older adults with PCNSL, who may be unfit to tolerate effective therapies for PCNSL.

A functional mammalian display screen identifies rare antibodies that stimulate NK cell-mediated cytotoxicity.

Therapies that boost the antitumor immune response have shown a great deal of success. Although most of these therapies have focused on enhancing T cell functions, there is a growing interest in developing therapies that can target other immune cell subsets. Like T cells, natural killer (NK) cells are cytotoxic effector cells that play a key role in the antitumor response.

Tumor metabolism and neurocognition in CNS lymphoma.

Background: The mechanistic basis for neurocognitive deficits in central nervous system (CNS) lymphoma and other brain tumors is incompletely understood. We tested the hypothesis that tumor metabolism impairs neurotransmitter pathways and neurocognitive function.

Methods: We performed serial cerebrospinal fluid (CSF) metabolomic analyses using liquid chromatography-electrospray tandem mass spectrometry to evaluate changes in the tumor microenvironment in 14 patients with recurrent CNS lymphoma, focusing on 18 metabolites involved in neurotransmission and bioenergetics.

Blood Coagulation Factor Fibrinogen in Tumor Pathogenesis of Central Nervous System B-Cell Lymphoma.

Central nervous system (CNS) lymphoma is an extranodal non-Hodgkin B-cell lymphoma characterized by malignant lymph tissue arising in the brain or spinal cord, associated with inflammation and blood-brain barrier (BBB) disruption. Although BBB disruption is known to occur in patients with CNS lymphoma, a direct link between these two has not been shown. Herein, abundant deposition of the blood coagulation protein fibrinogen around B-cell lymphoma was detected in CNS lymphoma patients and in the CNS parenchyma in an orthotopic mouse model.

Cutaneous T-Cell Lymphoma PDX Drug Screening Platform Identifies Cooperation between Inhibitions of PI3Kα/δ and HDAC.

Cutaneous T-cell lymphoma is a form of non-Hodgkin lymphoma that manifests initially in the skin and disseminates systemically as the disease progresses. Mycosis fungoides and Sézary syndrome are the most common subtypes of cutaneous T-cell lymphoma. Advanced mycosis fungoides and Sézary syndrome are life threatening with few treatment options.

On point in primary CNS lymphoma.

Primary CNS lymphoma (PCNSL) is an aggressive brain tumor that represents a significant challenge both to elucidate its biological pathogenesis as well as to develop definitive precision medicines with minimal collateral toxicity. We highlight the key issues in diagnosis and treatment and focus on emerging technologies, current options among consolidation strategies, and biological agents. We anticipate that further development of molecular diagnostics and molecular imaging approaches that elucidate minimal residual disease in brain parenchyma, leptomeninges, intraocular compartments and even bone marrow will greatly impact the delivery and timing of cytotoxic and biological therapies.

An audit of retinal lymphoma treatment at the University of California San Francisco.

Background/objectives: To evaluate retinal lymphoma treatment at the University of California San Francisco.

Subjects/methods: Prospective observational audit. Patients were treated systemically, usually with: methotrexate, temozolomide, and rituximab induction; etoposide consolidation; and maintenance with lenalidomide or another immunomodulatory agent.

Evolving Treatments for Primary Central Nervous System Lymphoma.

Primary central nervous system (CNS) lymphoma (PCNSL) is an aggressive form of non-Hodgkin lymphoma that remains confined to the CNS neuroaxis during its natural history of disease and is therefore considered stage IE disease. PCNSL is diffuse large B-cell lymphoma (DLBCL) morphology in more than 95% of patients and is designated primary diffuse large B-cell lymphoma of the CNS on the basis of the 2017 World Health Organization classification of hematopoietic and lymphoid tumors. Rapidly evolving therapeutic paradigms have been linked to evidence of progress in PCNSL, a disease long considered to be incurable.