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Abiraterone and enzalutamide are used to treat advanced or metastatic prostate cancer. We compared hospitalizations during initial treatment among 19,775 U.S. veterans. We found that when accounting for prior hospitalizations, patients started on enzalutamide were hospitalized less frequently compared to abiraterone. Background: Abiraterone and enzalutamide are second generation androgen receptor pathway inhibitors (ARPIs) used to treat advanced or metastatic prostate cancer. Without head-to-head comparative studies identifying 1 agent as preferred initial therapy, physician preferences guide initial ARPI choice. This study compares hospitalizations among patients treated initially with abiraterone versus enzalutamide. Patients and Methods: United States veterans treated with abiraterone or enzalutamide between May 13, 2011 and December 31, 2019; then compared hospitalization rate during first treatment with ARPI in the Veterans Healthcare Administration. Baseline incidence rate of hospitalization was determined from data 1 year prior to ARPI. Incidence Rate Difference (IRD) was calculated using χ2 test and difference in IRD using Poisson Regression. Results: 19,775 veterans were identified; 13,527 (68.4%) were initially treated with abiraterone and 6248 (31.6%) initially with enzalutamide. The enzalutamide cohort was older (75.8 vs. 74.5 years, P < .001) and had higher baseline comorbidities at ARPI initiation (4.4 vs. 4.0, P < .001). Patients were treated with enzalutamide longer than abiraterone (median 9.0 vs. 8.0 months, P < .001). Total hospitalizations increased from 465 per 1000 person-years in the year prior to treatment with abiraterone to 567 during treatment. Total hospitalizations increased from 417 per 1000 person-years in the year prior to treatment with enzalutamide to 430 during treatment. Total rate of hospitalization increased 22% for abiraterone compared to a 3% increase for enzalutamide in the 12 months after ARPI initiation (P < .0001). Abiraterone was associated with greater increase in rates of acute heart failure, atrial fibrillation, acute kidney injur y, urinar y tract infections, sepsis, and pneumonia. Conclusion: By comparing the rate of hospitalization before vs. during treatment, real world analyses identified a 22% versus 3% increase in hospitalizations with abiraterone compared to enzalutamide respectively, despite being used in a younger population with less comorbid disease. Abiraterone was also associated with higher risk of infections, a novel finding. [ABSTRACT FROM AUTHOR]

A response from authors of the article "Progressive multifocal leukoencephalopathy associated with brentuximab vedotin therapy: a report of 5 cases from the Southern Network on Adverse Reactions (SONAR) project" in 2014 issue of the periodical is presented.

Choosing Wisely® is a medical stewardship initiative led by the American Board of Internal Medicine Foundation in collaboration with professional medical societies in the United States. The American Society of Hematology (ASH) released its first Choosing Wisely® list in 2013. Using the same evidence-based methodology as in 2013, ASH has identified 5 additional tests and treatments that should be questioned by clinicians and patients under specific, indicated circumstances. The ASH 2014 Choosing Wisely® recommendations include: (1) do not anticoagulate for more than 3 months in patients experiencing a first venous thromboembolic event in the setting of major, transient risk factors for venous thromboembolism; (2) do not routinely transfuse for chronic anemia or uncomplicated pain crises in patients with sickle cell disease; (3) do not perform baseline or surveillance computed tomography scans in patients with asymptomatic, early-stage chronic lymphocytic leukemia; (4) do not test or treat for heparin-induced thrombocytopenia if the clinical pretest probability of heparin-induced thrombocytopenia is low; and (5) do not treat patients with immune thrombocytopenia unless they are bleeding or have very low platelet counts. [ABSTRACT FROM AUTHOR]

Choosing Wisely® is a medical stewardship and quality improvement initiative led by the American Board of Internal Medicine Foundation in collaboration with leading medical societies in the United States. The ASH is an active participant in the Choosing Wisely® project. Using an iterative process and an evidence-based method, ASH has identified 5 tests and treatments that in some circumstances are not well supported by evidence and which in certain cases involve a risk of adverse events and financial costs with low likelihood of benefit. The ASH Choosing Wisely® recommendations focus on avoiding liberal RBC transfusion, avoiding thrombophilia testing in adults in the setting of transient major thrombosis risk factors, avoiding inferior vena cava filter usage except in specified circumstances, avoiding the use of plasma or prothrombin complex concentrate in the nonemergent reversal of vitamin K antagonists, and limiting routine computed tomography surveillance after curativeintent treatment of non-Hodgkin lymphoma. We recommend that clinicians carefully consider anticipated benefits of the identified tests and treatments before performing them. [ABSTRACT FROM AUTHOR]

Erythropoisis stimulating agent (ESA) use was addressed in Food and Drug Administration (FDA) Oncology Drug Advisory Committee (ODAC) meetings between 2004 and 2008. FDA safety-focused regulatory actions occurred in 2007 and 2008. In 2007, black box warnings advised of early death and venous thromboembolism (VTE) risks with ESAs in oncology. In 2010, a Risk Evaluation Strategies (REMS) was initiated, with cancer patient consent that mortality and VTE risks were noted with ESAs. We report warnings and REMS impacts on ESA utilization among Veterans Administration (VA) cancer patients with chemotherapy-induced anemia (CIA). Data were from Veterans Affairs database (2003–2012). Epoetin and darbepoetin use were primary outcomes. Segmented linear regression was used to estimate changes in ESA use levels and trends, clinical appropriateness, and adverse events (VTEs) among chemotherapy-treated cancer patients. To estimate changes in level of drug prescription rate after policy actions, model-specific indicator variables as covariates based on specific actions were included. ESA use fell by 95% and 90% from 2005, for epoetin and darbepoetin, from 22% and 11%, respectively, to 1% and 1%, respectively, among cancer patients with CIA, respectively (p<0.01). Following REMS in 2010, mean hematocrit levels at ESA initiation decreased from 30% to 21% (p<0.01). Black box warnings preceded decreased ESA use among VA cancer patients with CIA. REMS was followed by reduced hematocrit levels at ESA initiation. Our findings contrast with privately- insured and Medicaid insured cancer patient data on chemotherapy-induced anemia where ESA use decreased to 3% to 7% by 2010–2012. By 2012, the era of ESA administration to VA to cancer patients had ended but the warnings remain relevant and significant. In 2019, oncology/hematology national guidelines (ASCO/ASH) recommend that cancer patients with chemotherapy-induced anemia should receive ESAs or red blood cell transfusions after risk-benefit evaluation. [ABSTRACT FROM AUTHOR]

Follicular lymphoma(FL) is themost common formof indolent non-Hodgkin lymphoma, yet it remains only partially characterized at the genomic level. To improve our understanding of the genetic underpinnings of this incurable and clinically heterogeneous disease, whole-exome sequencingwas performed on tumor/normal pairs from a discovery cohort of 24 patients with FL. Using these data and mutations identified in other B-cell malignancies, 1716 genes were sequenced in 113 FL tumor samples from 105 primarily treatment-naive individuals. We identified 39 genes that were mutated significantly above background mutation rates. CREBBP mutations were associated with inferior PFS. In contrast, mutations in previously unreported HVCN1, a voltage-gated proton channel-encoding gene and B-cell receptor signaling modulator, were associated with improved PFS. In total, 47 (44.8%) patients harbor mutations in the interconnected B-cell receptor (BCR) and CXCR4 signaling pathways. Histone gene mutations were more frequent than previously reported (identified in 43.8% of patients) and often co-occurred (17.1% of patients).Anovel, recurrent hotspotwas identified at a posttranslationally modified residue in the histone H2B family. This study expands the number of mutated genes described in several known signaling pathways and complexes involved in lymphoma pathogenesis (BCR, Notch, SWitch/sucrose nonfermentable (SWI/SNF), vacuolar ATPases) and identified novel recurrent mutations (EGR1/2, POU2AF1, BTK, ZNF608, HVCN1) that require further investigation in the context of FL biology, prognosis, and treatment. [ABSTRACT FROM AUTHOR]

Peripheral T-cell lymphomas ( PTCL) have suboptimal outcomes using conventional CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. The anti-folate pralatrexate, the first drug approved for patients with relapsed/refractory PTCL, provided a rationale to incorporate it into the front-line setting. This phase 2 study evaluated a novel front-line combination whereby cyclophosphamide, etoposide, vincristine and prednisone ( CEOP) alternated with pralatrexate ( CEOP-P) in PTCL. Patients achieving a complete or partial remission ( CR/ PR) were eligible for consolidative stem cell transplantation ( SCT) after 4 cycles. Thirty-three stage II- IV PTCL patients were treated: 21 PTCL-not otherwise specified (64%), 8 angioimmunoblastic T cell lymphoma (24%) and 4 anaplastic large cell lymphoma (12%). The majority (61%) had stage IV disease and 46% were International Prognostic Index high/intermediate or high risk. Grade 3-4 toxicities included anaemia (27%), thrombocytopenia (12%), febrile neutropenia (18%), mucositis (18%), sepsis (15%), increased creatinine (12%) and liver transaminases (12%). Seventeen patients (52%) achieved a CR. The 2-year progression-free survival and overall survial, were 39% (95% confidence interval 21-57) and 60% (95% confidence interval 39-76), respectively. Fifteen patients (45%) (12 CR) received SCT and all remained in CR at a median follow-up of 21·5 months. CEOP-P did not improve outcomes compared to historical data using CHOP. Defining optimal front line therapy in PTCL continues to be a challenge and an unmet need. [ABSTRACT FROM AUTHOR]

Background Increasingly, clinicians and researchers are using administrative data for clinical and outcomes research. However, they continue to question the accuracy of using International Classification of Diseases 9th Revision (ICD-9) codes alone to capture diagnoses, especially venous thromboembolism (VTE), in administrative data. Objectives We tested the hypothesis that incorporation of treatment data and/or common procedural terminology (CPT) codes could improve accuracy of administrative data in detecting VTE. Research Design Using the Veterans Affairs Central Cancer Registry, we compared three competing algorithms by performing three cross-sectional studies. Algorithm 1 identified patients by ICD-9 codes alone. Algorithm 2 required VTE treatment in addition to ICD-9 codes. Algorithm 3 required a VTE diagnostic CPT code in addition to treatment and ICD-9 criteria. Results The accuracy of ICD-9 codes alone for detection of VTE was marginal, with a PPV of 72%. The PPV was improved to 91% after addition of treatment data (algorithm 2). As compared to algorithm 2, addition of CPT codes (algorithm 3) did not significantly increase the accuracy of detecting VTE (PPV 92%), but decreased sensitivity from 72% to 67%. Conclusions Accuracy of VTE detection significantly improved with addition of treatment data to ICD-9 codes. This approach should facilitate use of administrative data to assess the incidence, epidemiology, and outcomes of VTE. Highlights • Use of administrative data is increasing for research and quality assessment. • Outcomes within administrative data can be captured using ICD-9 coding. • This algorithm captures VTE outcomes with a PPV of 91%. • This algorithm facilitates accurate identification of VTE in administrative data. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined progressive multifocal leucoencephalopathy (PML) in chronic lymphocytic leukaemia (CLL) patients treated with ibrutinib, a small molecule irreversible inhibitor of Bruton tyrosine kinase (BTK). PML is described as a rare infection of the central nervous system (CNS). Also mentioned are therapeutic uses of ibrutinib and the clinical outcomes for patients with ibrutinib-associated PML.

The article focuses on a research which investigates association between body mass index (BMI) and relative dose-intensity with outcomes of febrile neutropenia and treatment-related mortality in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, doxorubicin and prednisone (RCHOP) as of December 2014. Topics discussed include significant differences in the average relative doseintensities, treatment-related mortality and toxicities among BMI groups.

The article focuses on racial difference in management of cytogenetic profiles for patients associated with multiple myeloma (MM). Topics include detection of deleted chromosome 13q by routine karyotype along with fluorescent in situ hybridization (FISH); examination of chromosomal abnormalities among MM patients through cytogenetic examination; observation of racial difference in metaphase cytogenetic of patients; and illustration of genetic differences influence over plasma cell malignancy.

Objective: To gain a better understanding of factors influencing clinicians' embryo transfer practices.Design: Cross-sectional survey.Setting: Web-based survey conducted in December 2008 of individuals practicing IVF in centers registered with the Society for Assisted Reproductive Technology (SART).Patient(s): None.Intervention(s): None.Main Outcome Measure(s): Prevalence of clinicians reporting following embryo transfer guidelines recommended by the American Society for Reproductive Medicine (ASRM), prevalence among these clinicians to deviate from ASRM guidelines in commonly encountered clinical scenarios, and practice patterns related to single embryo transfer.Result(s): Six percent of respondents reported following their own, independent guidelines for the number of embryos to transfer after IVF. Of the 94% of respondents who reported routinely following ASRM embryo transfer guidelines, 52% would deviate from these guidelines for patient request, 51% for cycles involving the transfer of frozen embryos, and 70% for patients with previously failed IVF cycles. All respondents reported routinely discussing the risks of multiple gestations associated with standard embryo transfer practices, whereas only 34% reported routinely discussing single embryo transfer with all patients.Conclusion(s): Although the majority of clinicians responding to our survey reported following ASRM embryo transfer guidelines, at least half would deviate from these guidelines in a number of different situations. [ABSTRACT FROM AUTHOR]

Context In 1998, a multidisciplinary team of investigators initiated RADAR (Research on Adverse Drug events And Reports), a clinically based postmarketing surveillance program that systematically investigates and disseminates information describing serious and previously unrecognized adverse drug and device reactions (ADRs). Objective To describe the structure, operations, and preliminary findings from the RADAR project and related dissemination efforts by pharmaceutical suppliers and the US Food and Drug Administration (FDA). Design After identifying a serious and unexpected clinical event suitable for further investigation, RADAR collaborators postulated clinical hypotheses and derived case series and incidence estimates from physician queries, published and unpublished clinical trials, published case reports, FDA databases, and manufacturer sales figures. Results RADAR investigators identified 16 types of serious ADRs among 1699 patients, of whom 169 (10%) died as a result of the reaction. Initial cases were identified by 7 RADAR investigators, 4 collaborating physicians, 2 attorneys, and by reviewing 3 published reports. Additional sources included queries of occupational health programs and medical directors of interventional cardiology laboratories (3 types of ADRs), published manuscripts and clinical trials (11 types of ADRs), review of medical records at a RADAR site (2 types of ADRs), unpublished clinical trial reports (3 types of ADRs), and reports from attorneys, family members, or patients (4 types of ADRs). Incidence estimates, ranging from 0.4% to 33%, were derived from 5 clinical trial reports, 2 physician queries, and 2 observational databases. Laboratory support for hypotheses included identification of 3 neutralizing antibodies and 3 histopathological findings. ADR reports were disseminated as 8 revised package inserts, 7 “dear doctor” letters, and 9 peer-reviewed articles. Conclusion A new, clinically based, hypothesis-driven approach to postmarketing surveillance may supplement existing regulatory surveillance systems and improve patient safety. [ABSTRACT FROM AUTHOR]

Mogamulizumab is a humanized antibody that targets CCR4, a transmembrane chemokine receptor predominantly expressed on effector T helper type 2 and malignant cutaneous T-cell lymphoma (CTCL) cells. This biologic was FDA approved for relapsed/refractory mycosis fungoides (MF)/Sézary syndrome (SS) in 2018. MARs are the most common adverse events reported; however, the clinicopathologic nature of these eruptions remains unclear. To inform future management and recognition of MAR, we report an update on our retrospective case series of MF/SS patients treated with mogamulizumab since its approval as standard of care. Among 24 CTCL (16 SS, 8 MF) patients, 17 developed MAR (68%). MAR development was associated with complete (11/17) or partial (4/17) responses, for an overall response rate (ORR) of 88% to mogamulizumab among patients with MAR. A lower ORR of 28% (2/7) was observed in patients that did not develop MAR. Median MAR time to onset (TTO) was 2.1 mo. (0.7–9.0). Median time to resolution (TTR) was 6.9 mo. (3.5–9.2) in 8/17 patients with MAR resolution. Five distinct but frequently concurrent clinical patterns were identified: lichenoid papules and plaques (9/17), MF-like lesions (9/17), photodistribution (7/17), psoriasiform plaques (7/17), and SS-like erythroderma (3/17). Histopathologic patterns included spongiotic (n=21), lichenoid (n=14), psoriasiform (n=10), and interface (n=8) features across 27 skin biopsies. Eosinophils (n=15), epithelioid granulomas (n=4), and bizarre bi- and multinucleated cells (n=6) that may represent highly activated macrophages were also noted. Although mild, features associated with CTCL were noted in all suspected MAR tissue samples [epidermotropism (n=10), exocytosis (n=12), and lymphoid atypia (n=16)]. When compared to baseline studies, flow cytometry analysis for circulating Sézary cells and TCR rearrangement studies in skin and blood were most often negative during suspected MAR despite the presence of CTCL-associated histological features, emphasizing the importance of ancillary studies in distinguishing MAR from CTCL. In conclusion, MAR may be characterized by distinct clinical, histopathologic, and molecular patterns. Notably, MAR can clinically mimic CTCL lesions and may occur more often in patients with clinical responses, highlighting the need for clinicians to rule out progressive disease vs. drug eruption in treating a condition that historically suffers from poor outcomes and treatment response. [ABSTRACT FROM AUTHOR]