IntroductionSurvival gaps in acute heart failure (AHF) continue to expand globally. Multinational heart failure (HF) registries have highlighted variations between countries. Whether discrepancies in ...HF practice and outcomes occur across different health systems (ie, private, public or universal healthcare) within a city or between countries remain unclear. Insight into organisational care is also scarce. With increasing public scrutiny of health inequalities, a study to address these limitations is timely.MethodKOLCOV-HF study prospectively compared patients with AHF in public (Nil Ratan Sircar Hospital (NRS)) versus private (Apollo Gleneagles Hospital (AGH)) hospitals of Kolkata, India, and one with universal health coverage in a socioeconomically comparable city of Coventry, England (University Hospitals Coventry & Warwickshire (UHCW)). Data variables were adapted from UK’s National HF Audit programme, collected over 24 months. Predictors of in-hospital mortality and length of hospitalisation were assessed for each centre.ResultsAmong 1652 patients, in-hospital mortality was highest in government-funded NRS (11.9%) while 3 miles north, AGH had significantly lower mortality (7.5%, p=0.034), similar to UHCW (8%). This could be attributed to distinct HF phenotypes and differences in clinical and organisational care. As expected, low blood pressure was associated with a significantly greater risk of death in patients served by public hospitals UHCW and NRS.ConclusionMarked differences in HF characteristics, management and outcomes exist intra-regionally, and between low–middle versus high-income countries across private, public and universal healthcare systems. Physicians and policymakers should take caution when applying country-level data locally when developing strategies to address local evidence-practice gaps in HF.
Haemato-oncology Unit, The Royal Marsden Hospital, Sutton, Surrey, United Kingdom
Correspondence: Moez Dungarwalla, The Royal Marsden Hospital, Sutton, Surrey, United Kingdom. E-mail: ...fareedaj{at}hotmail.com
The combination of high dose methylprednisolone and rituximab induces superior overall (93%) and complete (14%) response rates compared to high dose methylprednisolone alone (overall 43%, complete remission 0%) in heavily pre-treated chronic lymphocytic leukemia patients with advanced disease. Despite its efficacy the combination is not easily manageable because of the high rate of opportunistic infections.
Summary
This retrospective, observational study evaluated patterns of inpatient versus outpatient tumour lysis syndrome (TLS) monitoring during venetoclax ramp‐up in 170 patients with chronic ...lymphocytic leukaemia. The primary outcome was clinical/biochemical TLS. Two clinical and four biochemical TLS occurred (4.1%). Five of the six events occurred in high‐risk patients, four occurred at 20 mg dose and three at the 6‐h time‐point. Inpatient versus outpatient TLS rates within the high‐risk subgroup were 15% and 8%. Risk category was the only predictor of TLS events in multivariate analysis. Outpatient escalation did not associate with clinically meaningful TLS events, suggesting outpatient escalation has manageable associated TLS risks, including in high‐risk cohorts. These observations require confirmation in larger studies.
Objectives
We sought to characterise the outcomes of patients with haematological malignancy and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in hospital in our regional ...network of 7 hospitals.
Methods
Consecutive hospitalised patients with haematological malignancy and SARS‐CoV‐2 infection were identified from 01/03/2020 to 06/05/2020. Outcomes were categorised as death, resolved or ongoing. The primary outcome was preliminary case fatality rate (pCFR), defined as the number of cases resulting in death as a proportion of all diagnosed cases. Analysis was primarily descriptive.
Results
66 Patients were included, overall pCFR was 51.5%. Patients ≥ 70 years accounted for the majority of hospitalised cases (42, 63%) and fatalities (25, 74%). Mortality was similar between females (52%) and males (51%). Immunosuppressive or cytotoxic treatment within 3 months of the diagnosis of SARS‐CoV‐2 infection was associated with a significantly higher pCFR of 70%, compared with 28% in those not on active treatment (P = .0013, 2 proportions z test).
Conclusions
Mortality rates in patients with haematological malignancy and SARS‐CoV‐2 infection in hospital are high supporting measures to minimise the risk of infection in this population.
Summary
Limited data exist on COVID‐19 vaccination efficacy in patients with acute myeloid leukemia and myelodysplasia with excess blasts (AML/MDS‐EB2). We report results from a prospective study, ...PACE (Patients with AML and COVID‐19 Epidemiology). 93 patients provided samples post‐vaccine 2 or 3 (PV2, PV3). Antibodies against SARS‐COV‐2 spike antigen were detectable in all samples. Neutralization of the omicron variant was poorer than ancestral variants but improved PV3. In contrast, adequate T‐cell reactivity to SARS‐COV‐2 spike protein was seen in only 16/47 (34%) patients PV2 and 23/52 (44%) PV3. Using regression models, disease response (not in CR/Cri), and increasing age predicted poor T cell response.
Melphalan flufenamide (melflufen), an alkylating peptide-drug conjugate, plus dexamethasone showed clinical activity and manageable safety in the phase 2 HORIZON study. We aimed to determine whether ...melflufen plus dexamethasone would provide a progression-free survival benefit compared with pomalidomide plus dexamethasone in patients with previously treated multiple myeloma.
In this randomised, open-label, head-to-head, phase 3 study (OCEAN), adult patients (aged ≥18 years) were recruited from 108 university hospitals, specialist hospitals, and community-based centres in 21 countries across Europe, North America, and Asia. Eligible patients had an ECOG performance status of 0-2; must have had relapsed or refractory multiple myeloma, refractory to lenalidomide (within 18 months of randomisation) and to the last line of therapy; and have received two to four previous lines of therapy (including lenalidomide and a proteasome inhibitor). Patients were randomly assigned (1:1), stratified by age, number of previous lines of therapy, and International Staging System score, to either 28-day cycles of melflufen and dexamethasone (melflufen group) or pomalidomide and dexamethasone (pomalidomide group). All patients received dexamethasone 40 mg orally on days 1, 8, 15, and 22 of each cycle. In the melflufen group, patients received melflufen 40 mg intravenously over 30 min on day 1 of each cycle and in the pomalidomide group, patients received pomalidomide 4 mg orally daily on days 1 to 21 of each cycle. The primary endpoint was progression-free survival assessed by an independent review committee in the intention-to-treat (ITT) population. Safety was assessed in patients who received at least one dose of study medication. This study is registered with ClinicalTrials.gov, NCT03151811, and is ongoing.
Between June 12, 2017, and Sept 3, 2020, 246 patients were randomly assigned to the melflufen group (median age 68 years IQR 60-72; 107 43% were female) and 249 to the pomalidomide group (median age 68 years IQR 61-72; 109 44% were female). 474 patients received at least one dose of study drug (melflufen group n=228; pomalidomide group n=246; safety population). Data cutoff was Feb 3, 2021. Median progression-free survival was 6·8 months (95% CI 5·0-8·5; 165 67% of 246 patients had an event) in the melflufen group and 4·9 months (4·2-5·7; 190 76% of 249 patients had an event) in the pomalidomide group (hazard ratio HR 0·79, 95% CI 0·64-0·98; p=0·032), at a median follow-up of 15·5 months (IQR 9·4-22·8) in the melflufen group and 16·3 months (10·1-23·2) in the pomalidomide group. Median overall survival was 19·8 months (95% CI 15·1-25·6) at a median follow-up of 19·8 months (IQR 12·0-25·0) in the melflufen group and 25·0 months (95% CI 18·1-31·9) in the pomalidomide group at a median follow-up of 18·6 months (IQR 11·8-23·7; HR 1·10 95% CI 0·85-1·44; p=0·47). The most common grade 3 or 4 treatment-emergent adverse events were thrombocytopenia (143 63% of 228 in the melflufen group vs 26 11% of 246 in the pomalidomide group), neutropenia (123 54% vs 102 41%), and anaemia (97 43% vs 44 18%). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) in the pomalidomide group, the most common of which were pneumonia (13 6% vs 21 9%), COVID-19 pneumonia (11 5% vs nine 4%), and thrombocytopenia (nine 4% vs three 1%). 27 12% patients in the melflufen group and 32 13% in the pomalidomide group had fatal treatment-emergent adverse events. Fatal treatment-emergent adverse events were considered possibly treatment related in two patients in the melflufen group (one with acute myeloid leukaemia, one with pancytopenia and acute cardiac failure) and four patients in the pomalidomide group (two patients with pneumonia, one with myelodysplastic syndromes, one with COVID-19 pneumonia).
Melflufen plus dexamethasone showed superior progression-free survival than pomalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma.
Oncopeptides AB.
We report a case of a 65-year-old woman who sustained a left neck of femur (NOF) fracture following low-energy trauma. Computed tomography (CT) scan for the neck, chest, abdomen and pelvis was normal ...apart from enlargement of the right lobe of the thyroid. Interestingly, thyroid function was normal. While waiting for the result of thyroid cytology and bone histology, the patient recovered well from the operation and started to engage well with physiotherapy. The result of the investigation showed presence of diffuse large B-cell lymphoma in the left NOF and right lobe of the thyroid. As the presence of lymphoma only in these two organs is extremely rare, it is not yet clear what is underlying mechanism for such association. Therefore, such observations may raise many future research questions as detailed in the discussion of this case report. This case also illustrates the importance of a multidisciplinary approach in identifying, evaluating, and treating unique and complex presentations of NOF fracture, with a focus on the patient’s history, clinical examination and applying diagnostic tools.
The impact of Coronavirus disease 2019 (COVID-19) on outcomes in patients with cancer remains unclear. Acute Myeloid Leukemia (AML)/high-risk myelodysplasia (MDS) are common hematological ...malignancies resulting in profound immunosuppression, which is exacerbated by intensive and less-intensive chemotherapy. Importantly, venetoclax based regimens have been increasingly used during the pandemic as a strategy to reduce patient hospitalization however, there is little information concerning the impact of such regimens on COVID-19 infection rates. We therefore opened a prospective clinical study (PACE), at the start of the current pandemic in April 2020 to characterize the risk of COVID-19 infection in patients with AML/MDS-EB2 receiving intensive or non-intensive treatment, including patients treated with venetoclax-based regimens.
The primary aim was to determine the incidence of COVID-19 in patients with AML /MDS-EB2 including both, prior to study entry and during treatment until 4 weeks after the last cycle of treatment. Secondary aims were to: characterize the presentation of COVID-19; define the severity and type of both non-COVID-19 and COVID-19 infections; and undertake an exploratory analysis to quantify the incidence of COVID-19 infection in patients receiving (less-intensive) venetoclax based regimens. All analysis conducted to date has been descriptive.
211/230 recruited patients had full treatment histories available, of whom 116 patients received intensive chemotherapy and 95 low intensity regimens. 48 patients received a venetoclax-based regimen. The median age of the non-intensive treatment arm was 72 years; (range 19.1-86.5) and of the intensive arm was 59 years (range 16.1-76.1). There were more cases of secondary AML and relapsed disease in the non-intensive arm as compared to the intensive arm.
25/226 evaluable patients tested positive for COVID-19 as defined by positive SARS-CoV2 PCR test, 10 with a prior diagnosis at study entry and 15 tested positive during the study. The incidence of COVID-19 infection for patients with AML/MDS-EB2 was 11.1% (90%CI: 7.8%-15.1%) (Table). A lower proportion of patients (n=6/91 6.6%) undergoing non-intensive treatment suffered COVID-19 as compared to those undergoing more intensive chemotherapy regimens (n=19/116, 16.4%). Specifically, only 3/48 (6.3%) patients undergoing a venetoclax regimen were infected with SARS-CoV2. The most common presenting symptoms of COVID-19 in this study, regardless of the intensity of chemotherapy, was fever and cough with 6/25 patients asymptomatic. The risk of death at 30 days following study entry in patients who had prior COVID-19 infection or who contracted COVID-19 during this period was 13.6%, compared to 3.9% in the overall cohort without COVID-19 infection.
There was a lower incidence of non-COVID-19 related infections in patients receiving venetoclax-based regimens, n=43 infections in 24 (50.0%) of patients; with 313 infections in 94 (81%) of intensively treated patients. The overall occurrence of non-COVID-19 infection in the non-intensive arm was 87 infections in 50 (54.9%) patients.
Our multi-center study provides real-world estimates for the incidence and presentation of COVID-19 infection in a cohort of patients with AML/MDS-EB2, and indicates a higher risk of death at 30 days in patients with prior COVID-19 infection prior to, or during treatment. Venetoclax based, and other non-intensive, regimens, increasingly implemented during the pandemic, to minimize patient exposure and reduce usage of hospital beds, appeared to be associated with a low incidence of COVID-19. Further follow-up will be required to understand the long-term impact of this strategy. Analysis of immune responses to COVID-19 infection and vaccination is on-going.
Acknowledgments: This study was funded by Cure Leukaemia under the Trials Acceleration Program (TAP), and grants from BMS and Blood Cancer UK.
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Loke: Novartis: Other: Travel; Janssen: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Daichi Sankyo: Other: Travel. Knapper: Pfizer: Consultancy, Speakers Bureau; Astellas: Ended employment in the past 24 months, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau. Khan: Abbvie: Honoraria; Astellas: Honoraria; Takeda: Honoraria; Jazz: Honoraria; Gilead: Honoraria; Novartis: Honoraria. Dillon: Amgen: Other: Research support (paid to institution); Astellas: Consultancy, Other: Educational Events , Speakers Bureau; Menarini: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Session chair (paid to institution), Speakers Bureau; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: educational events; Jazz: Other: Education events; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Research Support, Educational Events; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees. Culligan: AbbVie Ltd: Honoraria, Speakers Bureau; Celgene Ltd: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Jazz Pharma: Honoraria, Speakers Bureau; Takeda UK Ltd: Honoraria, Speakers Bureau. McMullin: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Other: clinical trial support, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AOP Orphan: Research Funding, Speakers Bureau. Murthy: Abbvie: Other: support to attend educational conferences.. Craddock: Novartis Pharmaceuticals: Other: Advisory Board ; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding.
Abstract
Background
Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a recently described phenomenon where no flow-limiting lesions are noted on coronary angiography in a ...patient with electrocardiogram changes, elevated cardiac biomarkers, and symptoms suggesting acute myocardial infarction. Patients with MINOCA can also potentially develop structural cardiac defects through ischaemic injury. Therefore, the absence of a flow-limiting lesion on angiography coupled with structural defects (e.g. apical ballooning) can very easily result in a diagnosis of Takotsubo cardiomyopathy (TTC). This can lead to potentially serious consequences since treatment options between TTC and MINOCA are different.
Case summary
We report a case of a patient presenting with features suggestive of TTC but where the final diagnosis was of a MINOCA that induced an apical ventricular septal defect (VSD). Reaching the correct diagnosis proved challenging given that there is no gold standard diagnostic modality for diagnosing MINOCA.
Conclusion
Imaging adjuncts played a vital role in both diagnosing the underlying MINOCA as well as revealing and planning closure of the resultant VSD. Cardiovascular magnetic resonance imaging played an instrumental role in establishing the patient’s primary pathology and in planning a remediation of the structural defect. Structural myocardial defects in a patient with a diagnosis of TTC should prompt clinicians to further investigate whether there is an underlying infarct aetiology (MINOCA).
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