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Journal of Investigative Medicine ; 70(1):134-134, 2022.
Article in English | Web of Science | ID: covidwho-1613039
Blood ; 138:2321, 2021.
Article in English | EMBASE | ID: covidwho-1582311


Background Based on early evidence of a high rate of coronavirus mortality in patients with acute myeloid leukaemia (AML) undergoing intensive chemotherapy (IC), the national health service (NHS) in the United Kingdom temporarily made venetoclax available as an alternative therapy, with the aim of reducing both mortality and healthcare resource use. From late April 2020, venetoclax was available to patients aged >16y with NPM1 mutation without FLT3 internal tandem duplication (ITD), patients aged >50y with NPM1, IDH1 or IDH2 mutations (regardless of FLT3 status) and patients aged >60y without favourable-risk cytogenetics. Venetoclax could be given with either azacitidine or low-dose cytarabine (LDAC), with the latter recommended mainly for patients with NPM1 mutation. We report a health-system-wide real world data collection for toxicity and patient outcomes across 65 NHS Hospitals. Methods Each patient was registered on a central NHS database. Clinicians certified that their patient met the above criteria, had not received previous AML treatment, and was fit for induction chemotherapy. Anonymised data were retrospectively collected by treating physicians. Venetoclax dose, duration and toxicity information was requested for the first 4 cycles of therapy. Response definitions were as per European Leukaemia Network (ELN) guidelines. A total of 870 patients have been registered on the scheme, with outcomes reported here for those with follow-up information at a data cut on 1st August 2021. Results There were 301 patients, median age 72y (range 34 - 90) with 62% male. The majority (81%) had an ECOG performance status of 0-1. AML was secondary to a previous haematological disorder in 33%, therapy-related in 10% and de novo in the remaining 57%. MRC cytogenetic risk was intermediate in 70% and adverse in 27%. NPM1 mutations were detected in 28% and FLT3-ITD in 12%. Next-generation sequencing results were available in 86% of patients, which detected mutations in IDH1 or IDH2 in 28%, ASXL1 in 20%, RUNX1 in 17% and TP53 in 12%. The ELN risk was favourable for 23%, intermediate for 30% and adverse for 44%. A majority received venetoclax in combination with azacitidine (85%), with the remaining 15% receiving LDAC. The LDAC cohort was enriched for de novo AML (76% vs 54%) and NPM1-mutated disease (56% vs 23%). Most patients (81%) followed the recommended initial schedule of venetoclax 100mg daily for 28 days in combination with posaconazole or voriconazole. Patients spent a median 14 days in hospital in cycle 1, then a median of 0 days for cycles 2-4. In cycles 1, 2, 3 and 4, the median number of days for recovery of neutrophils to >0.5x10 9/L was 33, 25, 24 and 14 respectively, and the median number of days to recovery of platelets to >50x10 9/L was 22, 3, 0 (no drop below 50) and 0. The composite complete remission (CR) / CR with incomplete haematological recovery (CRi) rate was 70%. MRD data is being collected. The best response was morphological leukaemia free state (MLFS) in 2%, partial remission in 7% and refractory disease in 11%. CR/CRi was higher in de novo (78%) compared to secondary AML (57%, p=0.02);NPM1 mutated (78% vs 67%, p=0.02) and IDH1/IDH2 mutated disease (85% vs 62%, p=0.02). ELN favourable risk patients had the highest CR/CRi rate (85%, intermediate 71%, adverse 60%, p=0.01). Median follow-up was 8.2 months (95%CI 7.8 - 9.0) with median overall survival (OS) 12.8 months (95%CI 10.9 - not reached). Mortality at day 30 was 5.7% and day 60 was 8.4%. 12-month overall survival was 51%, increasing to 71% in those who achieved CR/CRi. Survival was poorer in secondary (HR 1.9, p <0.01) and therapy-related AML (HR 2.1, p=0.02), better in NPM1 mutated (HR 0.6, p=0.02) and IDH mutated (HR 0.5, p=0.02) disease and poorer with TP53 mutation (HR 2.0, p=0.01). Overall survival did not differ for patients treated with LDAC compared to azacitidine (HR 1.1, p=0.7). Conclusion This large real-world study demonstrates CR/CRi and survival rates comparable to those reported in prospective clinical trials. Importantly, during t e COVID-19 pandemic, the adoption of venetoclax regimens permitted the great majority of treatment to be delivered as an outpatient with significant resource saving at a time of critically constrained inpatient resources. The data support prospective comparisons of venetoclax-based regimens to IC in fit adults with AML particularly in older patients with de novo AML, NPM1-mutated and IDH-mutated disease. [Formula presented] Disclosures: Belsham: Celgene: Other: meeting attendance;Abbvie: Other: meeting attendance. Khan: Abbvie: Honoraria;Astellas: Honoraria;Takeda: Honoraria;Jazz: Honoraria;Gilead: Honoraria;Novartis: Honoraria. Khwaja: Pfizer: 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;Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Astellas: 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. Latif: Kite: Consultancy, Honoraria, Speakers Bureau;Jazz: Consultancy, Honoraria;Daiichi Sankyo: Consultancy, Honoraria;Novartis: Consultancy, Honoraria;Amgen: Consultancy, Honoraria;Abbvie: Consultancy, Honoraria;Astellas: Consultancy, Honoraria, Speakers Bureau;Takeda UK: Speakers Bureau. Loke: Pfizer: Honoraria;Amgen: Honoraria;Janssen: Honoraria;Novartis: Other: Travel;Daichi Sankyo: Other: Travel. Murthy: Abbvie: Other: support to attend educational conferences. Smith: ARIAD: Honoraria;Pfizer: Speakers Bureau;Daiichi Sankyo: Speakers Bureau. Whitmill: Daiichi-sankyo: Other: travel fees;EHA in stockholm: Other: conference support. Craddock: Novartis Pharmaceuticals: Other: Advisory Board;Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dillon: Shattuck Labs: Membership on an entity's Board of Directors or advisory committees;Jazz: Other: Education events;Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: educational events;Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Session chair (paid to institution), Speakers Bureau;Menarini: Membership on an entity's Board of Directors or advisory committees;Astellas: Consultancy, Other: Educational Events, Speakers Bureau;Amgen: Other: Research support (paid to institution);Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Research Support, Educational Events.

British Journal of Haematology ; 193:166-167, 2021.
Article in English | Web of Science | ID: covidwho-1227372
British Journal of Haematology ; 193:109-109, 2021.
Article in English | Web of Science | ID: covidwho-1227371
British Journal of Dermatology ; 183(SUPPL 1):211-212, 2020.
Article in English | EMBASE | ID: covidwho-1093696


The COVID-19 pandemic heralded a new era of working within the National Health Service, and almost overnight deconstructed long-established routines. One of the most alarming trends to emerge is a reduction in cancer diagnoses vs. the period prior to the outbreak. In some countries, this effect has been most pronounced for skin cancers. With the onset of social distancing, the need to reduce hospital footfall and > 50% staff redeployment, our skin cancer service and red flag (RF) pathway was forced to redefine. Working from newly established guidelines, patients with skin cancer were risk stratified, taking into account any comorbidities that may increase susceptibility to COVID-19. Mohs surgery and the regional melanoma sentinel lymph node biopsy service were suspended. Treatment delays were reported to and centralized within the newly adapted telelink multidisciplinary meeting (MDM). Given such exceptional service disruption, we sought to evaluate the RF 'journey' during the pandemic. We retrospectively analysed RF referrals into our department from 25 March to 14 June 2020, comparing these with the same 3-month period in 2019. During lockdown there were 349 RF referrals from primary care, compared with 667 RF referrals in the corresponding 2019 period, with a 29% increase in MDM cases. In 2019, we diagnosed 14 squamous cell carcinomas (SCCs) and six melanomas, with a mean time from referral to outpatient assessment of 38 days, and 88 days to definitive surgical treatment. During lockdown we had capacity for 54 RF cases to be assessed face-to-face weekly. Thirteen SCCs and four melanomas were diagnosed, with the majority seen within 2 weeks. Pending histology for lesions clinically suggestive of SCC and melanoma, these figures may increase to 17 and seven, respectively. The higher pick-up rate during lockdown was despite only 21% of confirmed RF cases having been assessed by the referring general practitioner in person. The COVID-19 pandemic compelled our RF service to streamline, allowing for rapid access to standalone RF clinics with increased see-and-treat capacity. These strategic adjustments in a continually fluid working environment parallel a disaster-recovery model of service delivery. In contrast to the more familiar quality improvement approach, disaster-recovery methodology allows for interventions and concepts for change to be identified at the outset, with ad hoc data gathering. Despite the obvious challenges, it is reassuring that our skin cancer service maintained essential and urgent cancer treatment. The success of this crisis-management approach serves as a reminder that even during adversity there can be opportunities for learning and service development.

Lancet Reg Health West Pac ; 5: 100056, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-939121


BACKGROUND: Countries with a high incidence of coronavirus 2019 (COVID-19) reported reduced hospitalisations for acute coronary syndromes (ACS) during the pandemic. This study describes the impact of a nationwide lockdown on ACS hospitalisations in New Zealand (NZ), a country with a low incidence of COVID-19. METHODS: All patients admitted to a NZ Hospital with ACS who underwent coronary angiography in the All NZ ACS Quality Improvement registry during the lockdown (23 March - 26 April 2020) were compared with equivalent weeks in 2015-2019. Ambulance attendances and regional community troponin-I testing were compared for lockdown and non-lockdown (1 July 2019 to 16 February 2020) periods. FINDINGS: Hospitalisation for ACS was lower during the 5-week lockdown (105 vs. 146 per-week, rate ratio 0•72 [95% CI 0•61-0•83], p = 0.003). This was explained by fewer admissions for non-ST-segment elevation ACS (NSTE-ACS; p = 0•002) but not ST-segment elevation myocardial infarction (STEMI; p = 0•31). Patient characteristics and in-hospital mortality were similar. For STEMI, door-to-balloon times were similar (70 vs. 72 min, p = 0•52). For NSTE-ACS, there was an increase in percutaneous revascularisation (59% vs. 49%, p<0•001) and reduction in surgical revascularisation (9% vs. 15%, p = 0•005). There were fewer ambulance attendances for cardiac arrests (98 vs. 110 per-week, p = 0•04) but no difference for suspected ACS (408 vs. 420 per-week, p = 0•44). Community troponin testing was lower throughout the lockdown (182 vs. 394 per-week, p<0•001). INTERPRETATION: Despite the low incidence of COVID-19, there was a nationwide decrease in ACS hospitalisations during the lockdown. These findings have important implications for future pandemic planning. FUNDING: The ANZACS-QI registry receives funding from the New Zealand Ministry of Health.