A First-in-Human Phase I Study of LOXO-338, an Oral Selective Bcl-2 Inhibitor, in Patients With Advanced Hematologic Malignancies.

Background: LOXO-338 is a novel, orally bioavailable small-molecule inhibitor of Bcl-2, designed to achieve selectivity for Bcl-2 over Bcl-xL, thus avoiding dose-limiting thrombocytopenia associated with Bcl-xL inhibition. This first-in-human, open-label, Phase 1 study investigated LOXO-338 in patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or B-cell non-Hodgkin lymphoma (NHL) (NCT05024045).

Patients And Methods: Patients with histologically confirmed advanced B-cell malignancies who had received ≥ 2 prior therapies were enrolled in Phase 1 dose escalation (interval 3 + 3 design).

Randomized Trial of Fixed-Dose Capecitabine Compared With Standard-Dose Capecitabine in Metastatic Breast Cancer: X-7/7 Trial.

Purpose: In metastatic breast cancer (MBC), oral capecitabine prescribed at the US Food and Drug Administration (FDA)-approved dose of 1,250 mg/m twice daily, 14 days on, 7 days off, is associated with poor tolerance. Mathematical models suggest that a fixed-dose (FD), dose-dense schedule may optimize efficacy. We conducted a randomized, open-label trial to compare the efficacy and tolerability of FD capecitabine, 1,500 mg twice daily, 7 days on, 7 days off (FD-7/7), with the FDA-approved dose and schedule (standard-dose [SD]-14/7).

Ibrutinib plus venetoclax in relapsed or refractory mantle cell lymphoma (SYMPATICO): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study.

Background: The combination of ibrutinib and venetoclax leverages complementary mechanisms of action and has shown promising clinical activity in mantle cell lymphoma (MCL). This study evaluated the efficacy and safety of ibrutinib-venetoclax compared with ibrutinib-placebo in patients with relapsed or refractory MCL.

Methods: SYMPATICO is a multicentre, randomised, double-blind, placebo-controlled, phase 3 study performed at 84 hospitals in Europe, North America, and Asia-Pacific.

Mosunetuzumab plus Pola-CHP compared with Pola-R-CHP in previously untreated DLBCL: final results from a Phase II study.

This Phase II study evaluated mosunetuzumab plus cyclophosphamide, doxorubicin, prednisone, and polatuzumab vedotin (Pola-M-CHP) versus Pola-rituximab (R)-CHP for first-line treatment of diffuse large B-cell lymphoma (DLBCL). Patients were randomized 2:1 to receive 6 cycles of Pola-M-CHP or Pola-R-CHP on Day 1 of each 21-day cycle. Mosunetuzumab was administered intravenously via step-up dosing during Cycle 1 and at 30 mg on Day 1 of subsequent cycles.

The emergence of bispecific T-cell engagers in the treatment of follicular and large B-cell lymphomas.

The rapid emergence of CD20-targeting T-cell engagers in follicular lymphoma and large B-cell lymphoma has further expanded the treatment options for patients with relapsed or refractory disease. Herein, we review and discuss the standard-of-care products and indications for mosunetuzumab, epcoritamab, and glofitamab. We provide a detailed overview of the registrational clinical trials, as well as a review of ongoing trials and likely future indications.

Analysing carbapenemases in hospital wastewater: Insights from intracellular and extracellular DNA using qPCR and digital PCR.

The widespread dissemination of carbapenem-resistant bacteria in wastewater systems, particularly from clinical sources, poses a significant public health risk. This study assessed the concentrations and distributions of extracellular DNA (exDNA) and intracellular DNA (iDNA) harboring carbapenemase genes in wastewater from six tertiary care hospitals in Germany. We collected a total of 36 samples, comprising six biological replicates from each hospital, and analysed them using quantitative real-time PCR (qPCR) and digital PCR (dPCR).

Safety and efficacy of eltrombopag in patients with post-CAR T cytopenias.

Background: While chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment outcomes of relapsed/refractory hematological malignancies, this therapy is associated with post-treatment cytopenias, which can pose a challenge to its safe administration. This study describes the management of post-CAR T cytopenias using the thrombopoietin mimetic eltrombopag.

Methods: This retrospective analysis included adult patients with lymphoma or myeloma who received CAR T-cell therapy at two academic medical centers.

Simulating a reference medium for determining bacterial growth in hospital wastewater for Raman spectroscopic investigation.

Wastewater is a very complex and diverse medium, which despite low nutrient density still harbors bacteria. Especially the wastewater from hospitals contains a high germ load. However, wastewater is also very variable and differs not only from day to day, but also from house to house.

Mosunetuzumab in combination with CHOP in previously untreated DLBCL: safety and efficacy results from a phase 2 study.

Up to 40% of patients with diffuse large B-cell lymphoma (DLBCL) are refractory to or relapse after first-line therapy, highlighting the need for better treatments. Mosunetuzumab is a CD20 × CD3 bispecific antibody that engages and redirects T cells to eliminate malignant B cells. In this phase 2, open-label study (NCT03677141), 40 patients (52.

Anatomical, phenological and genetic aspects of the host-parasite relationship between (Hymenoptera) and (Strepsiptera).

is an endoparasite of the mining bee with extreme sexual dimorphism and hypermetamorphosis. Its population structure, parasitization mode, genetic diversity and impact on host morphology were examined in nesting sites in Germany to better understand this highly specialized host–parasite interaction. The shift in host emergence due to stylopization was proven to be especially strong in .

Overcoming Barriers to Referral for Chimeric Antigen Receptor T Cell Therapy in Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma.

Diffuse large B cell lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin lymphoma. Although outcomes to frontline therapy are encouraging, patients who are refractory to or in relapse after first-line therapy experience inferior outcomes. A significant proportion of patients treated with additional lines of cytotoxic chemotherapy ultimately succumb to their disease, as established in the SCHOLAR-1 study.

Evaluation of the Durability of the Immune Humoral Response to COVID-19 Vaccines in Patients With Cancer Undergoing Treatment or Who Received a Stem Cell Transplant.

Importance: The durability of the antibody response to COVID-19 vaccines in patients with cancer undergoing treatment or who received a stem cell transplant is unknown and may be associated with infection outcomes.

Objective: To evaluate anti-SARS-CoV-2 spike protein receptor binding domain (anti-RBD) and neutralizing antibody (nAb) responses to COVID-19 vaccines longitudinally over 6 months in patients with cancer undergoing treatment or who received a stem cell transplant (SCT).

Design, Setting, And Participants: In this prospective, observational, longitudinal cross-sectional study of 453 patients with cancer undergoing treatment or who received an SCT at the University of Kansas Cancer Center in Kansas City, blood samples were obtained before 433 patients received a messenger RNA (mRNA) vaccine (BNT162b2 or mRNA-1273), after the first dose of the mRNA vaccine, and 1 month, 3 months, and 6 months after the second dose.

[Achalasia Update].

Achalasia Update The neurodegenerative disease achalasia (obsolete: "cardiac spasm") is the second most common functional disease of the esophagus after reflux disease. It is associated with an extremely high level of suffering for the patient. Pathophysiologically, it is a combination of a lack of swallowing-reflex relaxation at the gastric entrance and disturbed peristalsis of the tubular esophagus.

Socioeconomic and Racial Disparity in Chimeric Antigen Receptor T Cell Therapy Access.

Chimeric antigen receptor (CAR) T cell therapy is changing the paradigm in hematologic malignancies, but disparities in access exist in the real-world setting. Efforts to address and eliminate these disparities will ensure availability of this life-saving therapy. This study aimed to determine patterns of racial/ethnic distribution, socioeconomic strata, insurance coverage, and travel time of CAR T cell recipients.

Estimating the Reach of a Manifold via its Convexity Defect Function.

The reach of a submanifold is a crucial regularity parameter for manifold learning and geometric inference from point clouds. This paper relates the reach of a submanifold to its convexity defect function. Using the stability properties of convexity defect functions, along with some new bounds and the recent submanifold estimator of Aamari and Levrard (Ann.

Delayed COVID-19 Respiratory Failure in Patients with Lymphoma on Rituximab-based Chemoimmunotherapy.

• COVID-19 can present with delayed onset of symptoms in patients with lymphoma receiving rituximab-based chemoimmunotherapy. • Despite delayed onset of symptoms with prolonged asymptomatic period, outcomes can be particularly severe, including respiratory failure, thrombotic complications, and death.

Clinical and Biomarker Results from Phase I/II Study of PI3K Inhibitor Alpelisib plus Nab-paclitaxel in HER2-Negative Metastatic Breast Cancer.

Purpose: mutations are common in breast cancer and promote tumor progression and treatment resistance. We conducted a phase I/II trial of alpelisib (α-specific PI3K inhibitor) plus nab-paclitaxel in patients with HER2-negative metastatic breast cancer (MBC).

Patients And Methods: Eligible patients had HER2-negative MBC with any number of prior chemotherapies.

Effects of filgrastim versus pegfilgrastim on outcomes of DA-R-EPOCH for non-Hodgkin's lymphoma.

Purpose: Our study aimed to compare the median and average last dose level reached with DA-R-EPOCH, which includes the chemotherapy agents etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab, in patients using filgrastim versus pegfilgrastim as febrile neutropenia primary prophylaxis.

Methods: A retrospective, single-center chart review from January 1, 2014, to September 30, 2019, at The University of Kansas Health System identified patients > 18 years old who received at least four cycles of DA-R-EPOCH in an inpatient or outpatient setting for any subtype of lymphoma along with at least one dose of filgrastim or pegfilgrastim. Data was collected to compare dosing levels reached, appropriate discontinuation of daily filgrastim when ANC > 5000 cells/mm, completion of at least twice weekly complete blood count (CBC) monitoring after chemotherapy administration, the incidence of infections, FN, hospitalizations from infections or FN, and bone pain.

Acquired factor V inhibitor in the setting of coronavirus disease 2019 infection.

Factor V inhibitors are a rare cause of life-threatening bleeding. We present a case of an acquired factor V inhibitor likely caused by coronavirus disease 2019 infection. Bleeding was manifested by severe anemia requiring frequent red-cell transfusion, left psoas muscle hematoma, and left retroperitoneal cavity hematoma.