Durable Objective Response to Lurbinectedin in Small Cell Bladder Cancer with TP53 Mutation: A Molecular-Directed Strategy.

Small cell bladder cancer (SCBC) is a rare and aggressive disease, often treated with platinum/etoposide-based chemotherapy. Key molecular drivers include the inactivation of onco-suppressor genes (, ) and amplifications in proto-oncogenes (). We report a patient with SCBC who achieved an objective and prolonged response to lurbinectedin, which has been approved for metastatic small cell lung cancer, after developing disease progression on cisplatin/etoposide and nivolumab/ipilimumab.

VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic): clinical review in a rapidly emerging field.

VEXAS syndrome is a recently described entity characterized by systemic inflammatory and hematologic manifestations. The disease was first characterized by Beck et al. in 2020 in a study characterizing 25 patients with undiagnosed adult-onset inflammatory syndromes.

Immunoassay Urine Drug Testing among Patients Receiving Opioids at a Safety-Net Palliative Medicine Clinic.

Background: Few studies have examined the use of immunoassay urine drug testing of cancer patients in palliative care clinics.

Objectives: We examined the frequency of immunoassay urine drug test (UDT) abnormalities and the factors associated with aberrancy at a safety-net hospital palliative medicine clinic.

Methods: A retrospective review of the electronic medical records of consecutive eligible patients seen at the outpatient palliative medicine clinic in a resource-limited safety-net hospital system was conducted between 1 September 2015 and 31 December 2020.

Advances in non-clear cell renal cell carcinoma management: From heterogeneous biology to treatment options.

Non-clear cell renal cell carcinoma (nccRCC) makes up nearly one quarter of all RCC subtypes, commonly impacts younger patients, and is often metastatic at presentation. Compared to clear-cell RCC (ccRCC), nccRCC typically has a worse prognosis in the metastatic setting, with overall survival durations that are ~10 months shorter. The nccRCC consists of a wide range of different histological subtypes, the majority of which are composed of papillary, chromophobe, renal medullary carcinoma, translocation RCC, collecting duct carcinoma and unclassified RCC.

Phase I Results of Bromodomain and Extra-Terminal Inhibitor PLX51107 in Combination with Azacitidine in Patients with Relapsed/Refractory Myeloid Malignancies.

Purpose: Treatment outcomes in patients with relapsed/refractory (R/R) myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) remains dismal. On the basis of both extensive preclinical data and emerging clinical data, treatment with bromodomain and extra-terminal domain inhibitors (BETi) is a potential approach for patients with high-risk myeloid malignancies.

Patients And Methods: We conducted a phase I trial to study the safety and efficacy of PLX51107 (BETi) and azacitidine combination therapy in patients with R/R AML and high-risk (HR) MDS and studied mechanisms of resistance to the combination therapy.

Adherence to Opioid Patient Prescriber Agreements at a Safety Net Hospital.

Patient prescriber agreements, also known as opioid contracts or opioid treatment agreements, have been recommended as a strategy for mitigating non-medical opioid use (NMOU). The purpose of our study was to characterize the proportion of patients with PPAs, the rate of non-adherence, and clinical predictors for PPA completion and non-adherence. This retrospective study covered consecutive cancer patients seen at a palliative care clinic at a safety net hospital between 1 September 2015 and 31 December 2019.

Incidence and Risk Factors for Pneumonitis Associated With Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer: A Single Center Experience.

Introduction: Immune checkpoint inhibitor (ICI) pneumonitis causes substantial morbidity and mortality. Estimates of real-world incidence and reported risk factors vary substantially.

Methods: We conducted a retrospective review of 419 patients with advanced non-small cell lung cancer (NSCLC) who were treated with anti-PD-(L)1 with or without anti-CTLA-4 therapy.

Stranger Things: New Roles and Opportunities for Androgen Receptor in Oncology Beyond Prostate Cancer.

The androgen receptor (AR) is one of the oldest therapeutic targets in oncology and continues to dominate the treatment landscape for advanced prostate cancer, where nearly all treatment regimens include some form of AR modulation. In this regard, AR remains the central driver of prostate cancer cell biology. Emerging preclinical and clinical data implicate key roles for AR in additional cancer types, thereby expanding the importance of this drug target beyond prostate cancer.

North American Blastic Plasmacytoid Dendritic Cell Neoplasm Consortium: position on standards of care and areas of need.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with historically poor outcomes and no worldwide consensus treatment approach. Unique among most hematologic malignancies for its frequent cutaneous involvement, BPDCN can also invade other extramedullary compartments, including the central nervous system. Generally affecting older adults, many patients are unfit to receive intensive chemotherapy, and although hematopoietic stem cell transplantation is preferred for younger, fit individuals, not all are eligible.

Therapeutic Management of Chronic Lymphocytic Leukemia Presenting with Recurrent Massive Ascites.

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative malignancy that is categorized by the production and accumulation of CD5+ monoclonal B cell lymphocytes, commonly in the spleen, bone marrow, and peripheral blood; these are morphologically mature lymphocytes with abnormal immune function. Ascites, although common in solid organ malignancies such as ovarian, breast, and gastrointestinal, is a rare clinical manifestation in hematological malignancies. The case presented herein describes an elderly male patient with CLL who presented with transudative ascites 7 years after the completion of chemotherapy.

CD123-directed allogeneic chimeric-antigen receptor T-cell therapy (CAR-T) in blastic plasmacytoid dendritic cell neoplasm (BPDCN): Clinicopathological insights.

Purpose: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a hematologic malignancy associated with overexpression of CD123. Allogeneic chimeric antigen receptor T cells (CAR-T) directed against CD123 in BPDCN have been studied in clinical trials. We performed post-mortem analysis of a patient treated with anti-CD123 CAR-T to elucidate cause of death, development of cytokine release syndrome (CRS), and tissue distribution of UCART123 cells.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN): A promising future in the era of targeted therapeutics.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy arising from precursor dendritic cells. BPDCN cells characteristically express several markers on their cell surfaces including CD123, CD4, and CD56. Because of its rarity and challenging clinical presentation, there was no standard of care in managing BPDCN for decades and its prognosis overall was poor.

Multimodal kidney-preserving approach in localised and locally advanced high-risk upper tract urothelial carcinoma.

Objectives: Multimodal kidney-preserving (MKP) strategies may be an option for patients with localised or locally advanced high-risk upper tract urothelial carcinoma (UTUC) who have a relative contraindication for nephroureterectomy (NU).

Materials And Methods: We studied patients with UTUC who were managed with MKP strategies, consisting of systemic anticancer therapy, with or without local/topical strategies after endoscopic control of intraluminal tumours. Primary end points were overall survival (OS) and progression-free survival (PFS).

Characteristics and outcomes of patients with blastic plasmacytoid dendritic cell neoplasm treated with frontline HCVAD.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a clinically aggressive blood cancer, often involving the skin, bone marrow, lymph nodes, and central nervous system (CNS) in 20% to 30% of patients. Despite significant progress in CD123- and BCL-2-targeted therapy, most patients are not cured without hematopoietic stem cell transplant (HSCT), and CNS relapses occur quite frequently. Combination approaches with targeted and chemotherapy agents plus incorporation of prophylactic CNS-directed therapy are urgently needed.

Evaluating tagraxofusp for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN).

Introduction: Unique among hematologic malignancies, blastic plasmacytoid dendritic cell neoplasm (BPDCN) affects multiple compartments including bone marrow, hematologic, lymphatic, dermatologic, and central nervous systems (CNS). Treating BPDCN is challenging, historically, as patients display refractoriness to chemotherapy and absence of long-term remissions in many cases not treated with hematopoietic stem cell transplantation. Discovering the prevalent overexpression of surface receptor CD123 (IL3-Rα) on BPDCN cells led to development of tagraxofusp, a novel anti-CD123 agent for patients with BPDCN.

Efficacy and safety of gemcitabine plus doxorubicin in patients with renal medullary carcinoma.

Introduction: Renal medullary carcinoma (RMC) is a rare and lethal renal cell carcinoma characterized by the loss of tumor suppressor SMARCB1. Molecular profiling studies have suggested that RMC cells may be vulnerable to therapies that generate DNA damage, such as the combination of the nucleoside analog gemcitabine, and topoisomerase inhibitor doxorubicin.

Patients And Methods: We retrospectively analyzed the records of patients with RMC treated with gemcitabine plus doxorubicin at our institution between January 2005 and September 2020.

Targeting CD123 in BPDCN: an emerging field.

Introduction: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy with historically poor outcomes for patients, often refractory to traditional chemotherapy. Recent research has focused on targeted therapy to improve responses and limit potential toxicity.

Areas Covered: CD123 (also known as IL-3 Rα) is a cell surface marker and attractive therapeutic target for many myeloid malignancies, particularly BPDCN, whose cells ubiquitously overexpress CD123.

CD303 (BDCA-2) - a potential novel target for therapy in hematologic malignancies.

Plasmacytoid dendritic cells (pDCs) serve as immunoregulatory antigen-presenting cells that play a role in various inflammatory, viral, and malignant conditions. Malignant proliferation of pDCs is implicated in the pathogenesis of certain hematologic cancers, specifically blastic plasmacytoid dendritic cell neoplasm (BPDCN) and acute myelogenous leukemia with clonal expansion of pDC (pDC-AML). In recent years, BPDCN and pDC-AML have been successfully treated with targeted therapy of pDC-specific surface marker, CD123.

Management and Outcomes of Hematological Immune-related Adverse Events: Systematic Review and Meta-analysis.

Data regarding clinical outcomes and management of hematological manifestations of immune checkpoint inhibition (ICI) is limited to case reports, series, and a few retrospective reviews. We aimed to determine the rate of response of hematological immune-related adverse events (irAEs) to immunosuppressive therapy. MEDLINE (OVID), EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to the present day.

Novel Therapeutic Approaches in Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): Era of Targeted Therapy.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy arising from the aberrant transformation of plasmacytoid dendritic cells (pDCs) and involving skin, bone marrow, lymph nodes, and central nervous system. Characteristically unique from other myeloid neoplasms, BPDCN cells express CD4, CD56, and CD123 as well as TCL-1 and TCF4 in almost all cases. Historically, this malignancy has exhibited a poor prognosis, with median survival of less than 2 years.

Prognostic Factors and Overall Survival After Pericardiocentesis in Patients With Cancer and Thrombocytopenia.

Pericardiocentesis is an important diagnostic and therapeutic tool for cancer-associated pericardial effusion. Limited safety and outcomes data exists regarding the management of malignancy-related pericardial effusion in patients with thrombocytopenia. Our study aimed to analyze prognostic factors and overall survival (OS) after pericardiocentesis in thrombocytopenic cancer patients.