CREST-UK: Real-world effectiveness, safety and outpatient delivery of CPX-351 for first-line treatment of newly diagnosed therapy-related AML and AML with myelodysplasia-related changes in the UK.

Favourable outcomes with CPX-351 versus conventional 7 + 3 were demonstrated in the pivotal phase III trial in adults aged 60-75 years with newly diagnosed, highrisk/secondary acute myeloid leukaemia (AML). As a complement to the clinical trial and to address important data gaps, the CPX-351 Real-World Effectiveness and SafeTy (CREST-UK; NCT05169307) study evaluated the use of CPX-351 in routine clinical practice in the UK, in 147 patients with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes. Best response of complete remission or complete remission with incomplete platelet or neutrophil recovery was achieved by 53% of evaluable patients. Kaplan-Meier median overall survival (OS) was 12.8 months (95% confidence interval 9.2-15.3). Fifty (34%) patients proceeded to haematopoietic cell transplantation (HCT); median OS landmarked from the HCT date was not reached. There were no new safety concerns with CPX-351 identified in CREST-UK. Patients treated with CPX-351 in the outpatient setting spent an average of 24.4, 16.7, 28.2, and 27.7 fewer days on the ward compared with inpatients during first induction, second induction, first consolidation, and second consolidation, respectively. The results from CREST-UK provide valuable insights into the effectiveness, safety, and outpatient delivery of CPX-351 in routine clinical practice in the UK.

Ibrutinib as first-line therapy for mantle cell lymphoma: a multicenter, real-world UK study.

ABSTRACT: During the COVID-19 pandemic, ibrutinib with or without rituximab was approved in England for initial treatment of mantle cell lymphoma (MCL) instead of immunochemotherapy. Because limited data are available in this setting, we conducted an observational cohort study evaluating safety and efficacy. Adults receiving ibrutinib with or without rituximab for untreated MCL were evaluated for treatment toxicity, response, and survival, including outcomes in high-risk MCL (TP53 mutation/deletion/p53 overexpression, blastoid/pleomorphic, or Ki67 ≥ 30%). A total of 149 patients from 43 participating centers were enrolled: 74.1% male, median age 75 years, 75.2% Eastern Cooperative Oncology Group status of 0 to 1, 36.2% high-risk, and 8.9% autologous transplant candidates. All patients received ≥1 cycle ibrutinib (median, 8 cycles), 39.0% with rituximab. Grade ≥3 toxicity occurred in 20.3%, and 33.8% required dose reductions/delays. At 15.6-month median follow-up, 41.6% discontinued ibrutinib, 8.1% due to toxicity. Of 104 response-assessed patients, overall (ORR) and complete response (CR) rates were 71.2% and 20.2%, respectively. ORR was 77.3% (low risk) vs 59.0% (high risk) (P = .05) and 78.7% (ibrutinib-rituximab) vs 64.9% (ibrutinib; P = .13). Median progression-free survival (PFS) was 26.0 months (all patients); 13.7 months (high risk) vs not reached (NR) (low risk; hazard ratio [HR], 2.19; P = .004). Median overall survival was NR (all); 14.8 months (high risk) vs NR (low risk; HR, 2.36; P = .005). Median post-ibrutinib survival was 1.4 months, longer in 41.9% patients receiving subsequent treatment (median, 8.6 vs 0.6 months; HR, 0.36; P = .002). Ibrutinib with or without rituximab was effective and well tolerated as first-line treatment of MCL, including older and transplant-ineligible patients. PFS and OS were significantly inferior in one-third of patients with high-risk disease and those unsuitable for post-ibrutinib treatment, highlighting the need for novel approaches in these groups.

Preventing cardiotoxicity in patients with breast cancer and lymphoma: protocol for a multicentre randomised controlled trial (PROACT).

INTRODUCTION: Anthracyclines are included in chemotherapy regimens to treat several different types of cancer and are extremely effective. However, it is recognised that a significant side effect is cardiotoxicity; anthracyclines can cause irreversible damage to cardiac cells and ultimately impaired cardiac function and heart failure, which may only be evident years after exposure. The PROACT trial will establish the effectiveness of the ACE inhibitor enalapril maleate (enalapril) in preventing cardiotoxicity in patients with breast cancer and non-Hodgkin's lymphoma (NHL) receiving anthracycline-based chemotherapy. METHODS AND ANALYSIS: PROACT is a prospective, randomised, open-label, blinded end-point, superiority trial which will recruit adult patients being treated for breast cancer and NHL at NHS hospitals throughout England. The trial aims to recruit 106 participants, who will be randomised to standard care (high-dose anthracycline-based chemotherapy) plus enalapril (intervention) or standard care alone (control). Patients randomised to the intervention arm will receive enalapril (starting at 2.5 mg two times per day and titrating up to a maximum dose of 10 mg two times per day), commencing treatment at least 2 days prior to starting chemotherapy and finishing 3 weeks after their last anthracycline dose. The primary outcome is the presence or absence of cardiac troponin T release at any time during anthracycline treatment, and 1 month after the last dose of anthracycline. Secondary outcomes will focus on cardiac function measured using echocardiogram assessment, adherence to enalapril and side effects. ETHICS AND DISSEMINATION: A favourable opinion was given following research ethics committee review by West Midlands-Edgbaston REC, Ref: 17/WM/0248. Trial findings will be disseminated through engagement with patients, the oncology and cardiology communities, NHS management and commissioning groups and through peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT03265574.

Adherence to guidelines across different specialties to prevent infections in patients undergoing immunosuppressive therapies.

BACKGROUND: Substantial numbers of patients are now receiving either immunosuppressive therapies or chemotherapy. There are significant risks in such patients of developing opportunistic infections or re-activation of latent infections, with higher associated morbidity and mortality. The aim of this quality improvement project was to determine how effective 5 different specialties were in assessing and mitigating risks of developing opportunistic infections or re-activation of latent infections in patients undergoing immunosuppressive therapies. METHODS: This was a single centre audit where records of patients attending clinics providing immunosuppressive therapies were reviewed for the following: evidence of screening for blood-borne virus [BBV] infections, varicella and measles immunity, latent/active TB or hypogammaglobulinaemia, and whether appropriate vaccines had been advised or various infection risks discussed. These assessments were audited against both national and international guidelines, or a cross-specialty consensus guideline where specific recommendations were lacking. Two sub-populations were also analysed separately: patients receiving more potent immunosuppression and black and minority ethnic [BME] patients,. RESULTS: For the 204 patients fulfilling the inclusion criteria, BBV, varicella/measles and latent TB screening was inconsistent, as was advice for vaccinations, with few areas complying with specialty or consensus guidelines. Less than 10% of patients in one specialty were tested for HIV. In BME patients screening for HIV [60%], measles [0%] and varicella [40%] immunity and latent [30%] or active [20%] TB was low. Only 38% of patients receiving potent immunosuppression received Pneumocystis prophylaxis, with 3 of 4 specialties providing less than 15% of patients in this category with prophylaxis. CONCLUSIONS: Compliance with guidelines to mitigate risks of infection from immunosuppressive therapies was either inconsistent or poor for most specialties. New approaches to highlight such risks and assist appropriate pre-immunosuppression screening are needed.

Use of Anticoagulants Remains a Significant Threat to Timely Hip Fracture Surgery.

INTRODUCTION: Hip fracture remains the biggest single source of morbidity and mortality in the elderly trauma population, and any intervention focused on quality improvement and system efficiency is beneficial for both patients and clinicians. Two of the variables contributory to improving care and efficiency are time to theater and length of stay, with the overall goal being to improve care as reflected within the achievement of best practice tariff. One of the biggest barriers to optimizing these variables is preinjury anticoagulation. METHOD: Building on our previous work with warfarin in this population, we utilized a regional hip fracture collaborative network collecting prospective data through the National Hip Fracture Database with custom fields pertaining to all agents, including novel oral anticoagulants. RESULTS: In all, 1965 hip fracture patients median age 83 years (1639 not anticoagulated) were admitted to the 5 centers over 12 months. Median length of stay was 20.71 days; time to theater 23.09 hours, and the populations (anticoagulated vs control) were evenly matched for injury. Anticoagulated patients were delayed to theater (P ≤ .001), were inpatients for longer (P ≤ .001) and gained less best practice tariff (P ≤ .05). All variables per agent were noted and the impact of each assessed. CONCLUSIONS: Despite the widespread use of newer anticoagulants, popular due to unmonitored reversal and administration, patients stay longer in hospital and wait longer for surgery than nonanticoagulated patients of the same age and injury. Contemporary perioperative practices impact negatively on the ability to perform timely surgery on hip fracture patients. We propose a guideline specific to the management of anticoagulation in the hip fracture population to aid the optimum preparation of patients for theater, achievement of timely surgery, and potentially reduce length of stay.

Pneumococcal bacteraemia: clinical and microbiological epidemiology in Dundee, Scotland.

OBJECTIVE: To report the incidence of drug resistant Streptococcus pneumoniae isolated from blood culture in Dundee, Scotland. We shall also review the clinical and laboratory findings in these cases. METHODS: A retrospective review was undertaken of all cases of S. pneumoniae bacteraemia identified in our local area during a three year period from August 1st, 1997 to July 31st, 2000 (107 cases.) Data was obtained from patient medical records, blood culture reports and results of Stoke's disk testing. Many organisms were also sent to the Scottish Meningococcus and Pneumococcus Reference Laboratory for serogrouping and determination of the minimum inhibitory concentration of common antibiotics. RESULTS: Annual incidence of bacteraemia was approximately 15.9-17.8 per 100000 population. Mortality was 33% (34 and 30% for those with pneumonia or meningitis, respectively). No relationship was seen between patient age and overall mortality. Factors relating to increased mortality were a high respiratory rate (p=0.01), high blood urea level (p=0.05) and the presence of confusion (p<0.01) on admission to hospital. The incidence of penicillin resistant S. pneumoniae was 7%, all of these isolates having low level resistance. Macrolide resistance was 8%. Neither were found to be increasing over the three year period. The most common serogroups were 23 (18%) and 14 (12%). CONCLUSIONS: The incidence of penicillin resistant S. pneumoniae isolated from blood culture in Dundee, Scotland, is similar to the UK average and did not appear to be rising between 1997 and 2000.