Characterization of recurrent cytomegalovirus reactivations post allogenic stem cell transplantation in a population with high seropositivity.

OBJECTIVES: This study aimed to characterize incidences of CMV reactivations within one year post-allo-SCT and identify risk factors for CMV second reactivation episode in population with high seropositivity where first CMV reactivation episode deemed to be high. METHODS: This retrospective cohort study analyzed data from 359 allo-SCT patients aged 14 and older admitted to a tertiary academic hospital. Data on demographic and clinical factors, CMV serostatus, conditioning regimens, graft-versus-host disease prophylaxis, engraftment time, and CMV reactivations were collected. RESULTS: First and second CMV reactivations occurred in 88.9% and 18.4% of post-allo-SCT patients respectively. Patients were stratified into two groups based on primary disease necessitating allo-SCT, patients with malignant (Group 1) and non-malignant (Group 2) hematological disease. Factors associated with the second reactivation included cord blood as a stem cell source, human leukocyte antigen mismatch, acute graft-versus-host disease, and hematological malignancies. Patients with non-malignant hematological disease displayed better outcomes, including a higher rate of spontaneous clearance of first CMV reactivation (70% versus 49.4%) and lower rates of second CMV reactivation (9.6% versus 31%) than those with malignant hematological disease. The one-year overall survival rate was 87.7% (95.5% in non-malignant hematological disease and 78.13% in malignant hematological disease). CONCLUSION: Our findings are concordant with previous local study in regard to high rate of first CMV reactivation post-allo-SCT. It appears that patients with nonmalignant hematological disease had better outcomes, such as lower second CMV reactivation and higher survival rates compared to patients with malignant hematological disease. Further investigation is needed to identify other factors affecting recurrent CMV reactivations in allo-SCT in patients with malignant hematological disease.

Advancing the understanding of venetoclax in t(11;14)-positive multiple myeloma: a comprehensive review of clinical evidence and future prospects.

Venetoclax is a selective inhibitor of the anti-apoptotic protein B-cell lymphoma 2 (BCL2), as a targeted therapy for multiple myeloma (MM) patients. It was initially approved by the United States Food and Drug Administration for the treatment of chronic lymphocytic leukemia in April 2016 and later for acute myeloid leukemia in October 2020. However, venetoclax is used as an off-label in a subset group of relapsed and refractory multiple myeloma (RRMM) patients with the presence of translocation t(11;14). Preclinical and clinical studies have highlighted the potential of venetoclax in the management of MM patients, with a specific focus on t(11;14) as a predictive biomarker for initiating venetoclax-based treatment. Later, several studies in RRMM patients that used venetoclax in combination with dexamethasone or/and proteasome inhibitors have shown promising results, in which management guidelines have included venetoclax as one of the options to treat MM patients. Hence, this review focuses on the use of venetoclax in RRMM, clinical efficacy, safety, dosing strategies, and predictive biomarkers for initiating venetoclax. Additionally, we discuss ongoing studies that are investigating different combination of venetoclax regimens in MM patients.

Zanubrutinib in Mantle Cell Lymphoma Management: A Comprehensive Review.

Purpose: The pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of zanbrutinib are described. Summary: Mantle cell lymphoma (MCL) is a mature B-cell lymphoma that is typically associated with unfavorable outcomes, and virtually all patients with MCL have refractory or relapsed disease despite aggressive treatment. The treatment paradigm for MCL has transformed dramatically over the past decade owing to rapid advancements in immunotherapy and molecular-targeted therapies. Zanubrutinib, a second-generation Bruton's tyrosine kinase inhibitor (BTKI) designated for mature B-cell non-Hodgkin's lymphoma (NHL), has drastically improved the survival outcomes in relapsed/refractory (R/R) MCL patients. This selective BTKI is a small molecule that functions by forming a covalent bond in the active site of BTK. The inhibition of BTK activity is essential for the signaling of B-cell antigen receptor (BCR) and cytokine receptor pathways. In a preclinical study, zanubrutinib inhibited malignant B-cell proliferation and reduced tumor growth. Zanubrutinib was granted FDA-accelerated approval based on the results of Phase I and II trials. The investigator-assessed overall response rate was 83.7%, of which 78% of patients achieved complete response. The median duration of response was 19.5 months, and the median progression-free survival was 22.1 months. The most common (≥20%) all-grade adverse events were low neutrophil count (46.5%), upper respiratory tract infection (38.4%), rash (36.0%), low white blood cell count (33.7%), and low platelet count (32.6%). Conclusion: Zanubrutinib is a selective, next-generation, orally active, irreversible BTK inhibitor. The selectivity of zanubrutinib and its superior efficacy, with a well-tolerated safety profile, have proven to be attractive options for other malignancies.

Late-onset cardiotoxicity in patients with HER2-positive metastatic breast cancer receiving trastuzumab-based therapy.

INTRODUCTION: Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) typically receive long-term trastuzumab treatment for several years. The aim of our study is to identify the incidence and characterize late-onset cardiotoxicity in patients with HER2-positive MBC receiving trastuzumab-based therapy. METHODS: We retrospectively reviewed charts of HER2-positive MBC patients who received >1 year of trastuzumab-based therapy at the Massachusetts General Hospital Cancer Center over three-year period. The primary endpoint was development of trastuzumab-induced cardiotoxicity (TIC). Secondary endpoints included time to TIC development, incidence/duration of trastuzumab interruption due to TIC, incidence of permanent discontinuation of trastuzumab due to TIC, clinic visit, or hospitalization due to TIC. RESULTS: Thirty-seven patients were included. Mean age was 56 years (range: 33-78 years, SD 9.5). Seven patients received prior doxorubicin and 14 patients received previous or concurrent breast irradiation. Mean duration of trastuzumab-based therapy was 57 months (range: 14-140 months, SD 39.3). Seven patients (18.9%) experienced TIC resulting in treatment interruption for two patients (28 and 78 days). The median time from starting trastuzumab therapy to TIC was 14 months (interquartile range: 11-29.5 months). The mean number of left ventricular ejection fraction (LVEF) assessment completed per year was 2.7 (range: 1.2-6.6, SD 1.1). CONCLUSION: Cardiotoxicity occurred in a minority of patients with HER2-positive MBC receiving trastuzumab-based therapy for more than one year. LVEF reductions to below the institutional lower limit of normal and therapy modifications were uncommon.

Ocular toxicities associated with antibody drug conjugates and immunotherapy in oncology: clinical presentation, pathogenesis, and management strategies.

INTRODUCTION: The development of molecularly targeted anticancer therapies and immunotherapy continues to revolutionize the treatment of cancer. FDA accelerated approvals of novel targeted therapies allowed for introduction of these agents into the clinic at a rapid rate. On-and off-target ocular toxicities are prevalent treatment-related adverse events of newer therapies including antibody drug conjugates (ADCs) and immunotherapy. Ocular toxicities associated with ADCs and immunotherapy have heterogeneous presentations and pathogenesis requiring unique and often complex monitoring, and management. AREAS COVERED: In this article, we provide an updated review of treatment-emergent ocular toxicity associated with new and novel oncologic therapies and summarize guidelines and best practice strategies for prevention, monitoring and management. A literature search was performed through PubMed, ClinicalTrials.gov, and FDA website (1 January 2017 to 10 May 2023) to identify relevant information. EXPERT OPINION: The implementation of a strategy for monitoring, prevention, and management of treatment-related ocular toxicities involves a multi-disciplinary, often cross-center approach. Communication with infusion nursing leadership, clinic staff, and eye care providers is crucial to the successful implementation of eye care plans to prevent and manage ocular toxicity.

Identifying gaps in vaccination perception after mandating the COVID-19 vaccine in Saudi Arabia.

OBJECTIVE: The burden of COVID-19 pandemic affected the globe, and it is unclear how it has impacted the general perception of other vaccines. We aimed to investigate the public awareness, knowledge, and attitude towards other complementary vaccines after the mandate of the COVID-19 vaccine. METHODS: A cross-sectional study was conducted in Saudi Arabia using a survey distributed via several social media platforms in June 2022. The questionnaire had three main sections; awareness; attitudes; and demographic information. Descriptive analysis was mainly used and supplemented with Chi-square test for correlation. All individuals over the age of 18 were eligible to participate in the study. RESULTS: A total of 1,045 participants from Saudi Arabia completed the survey. Of the respondents, 55.9% were female, and 95% were Saudi citizens. Public awareness towards vaccines after the mandate of COVID-19 vaccine was the highest with the influenza vaccine (98.2%), followed by human papillomavirus (HPV) (40.7%), tetanus, diphtheria, and pertussis (Tdap) (37.2%), and lastly, pneumococcal vaccine (17%). More than 50% of the participants expressed their willingness to receive any of the four vaccines if they knew about the benefits related to these vaccines. CONCLUSION: The study showed that participants were willing to receive the vaccination if they were aware of the general benefits of vaccinations. Therefore, health education and campaigns toward recommended vaccines for high-risk group are essential and needed.

Evaluation of Emergency Department Visits by Oncology Patients: A Running Comparison to Admissions and ED Visits Under the CMS OP-35 Ruling.

Background: Cancer is the second leading cause of death in the United States. The incidence of emergency department (ED) visits by oncology patients has grown over the past years. Some ED visits are medically unnecessary and could be prevented with improved prevention measures. Objectives: To evaluate the incidence and causes of ED visits by cancer patients and evaluate outcomes and disposition of ED visits. Methods: This single-center, retrospective chart review was conducted in a tertiary medical hospital. We collected data using an electronic medical record and included oncology patients with active cancer who had ED visits from January 1, 2018, to December 31, 2018. Key data collection included baseline demographics; type of malignancy; main chief complaint; clinic visit history; current and past ED visits; treatment and supportive care data; and disposition status if admitted. Pregnant patients, patients without active cancer, and patients who received outpatient care at clinics other than the University of Arizona Cancer Center were excluded. Results: This chart review study screened 1,659 encounters and included 205 encounters. Approximately 70% of the encounters were solid tumor patients and 30% were hematologic malignancies. Nearly 50% of the patients with hematologic malignancies had preventable ED visits while 32.8% of solid tumor patients had preventable ED visits. The most common preventable ED visit reasons in both groups were pain, fever, nausea, vomiting, and dehydration. Almost 50% of the patients in both groups were hospitalized with a median length of stay of 3 days. The majority of admitted patients were discharged home in both the solid tumor (82.3%) and hematologic malignancy (83.8%) groups. Conclusion: This study showed that the rate of preventable visits was numerically higher in the hematologic cancer group compared with the solid tumor group. These findings highlight the potential need for implementing prevention measures in the future.