ABSTRACT
Background: Venetoclax (Ven) in combination with hypomethylating agents, such as azacitidine (Aza) and low dose cytarabine (LDAC) has been shown to be effective therapy in acute myeloid leukaemia (AML) and has become standard of care for newly-diagnosed patients unfit for intensive chemotherapy (DiNardo et al., 2020;Wei et al., 2019;Pollyea et al., 2020). Efficacy has also been shown in the relapsed/refractory (R/R) setting in more limited data sets (Báez-Gutiérrez et al., 2021;Pollyea et al., 2020, Stahl et al., 2020;DiNardo et al., 2019). Ven combination therapy has become widely used in newly-diagnosed patients in the UK since its approval during the COVID-19 pandemic as an alternative to intensive chemotherapy and subsequently for patients unfit for intensive therapy. Aims: We describe the characteristics and outcomes of patients with AML or high risk myelodysplastic syndrome (HRMDS) receiving Ven combinations in frontline and R/R settings to provide real-world insight into their use in UK clinical practice. Methods: A retrospective analysis was performed of all patients with AML or HR-MDS who received Ven combination therapy at University College London Hospital between April 2020 and September 2021. Patient demographics, treatment history and bone marrow results were obtained from electronic health care and laboratory records. Disease stratification and response assessments were made as per European LeukemiaNet (ELN) criteria (Döhner et al., 2017). Results: At the time of analysis, 95 patients received Ven combinations (61 as frontline treatment and 34 for R/R AML), with a median follow up of 14 months. The majority of patients in both groups had adverse risk ELN classification (70.5% of frontline patients, 64.7% of R/R) and received Ven-Aza (100% frontline and 91.1% R/R) (Table 1). The median ages were 72 and 59 years respectively. The incidence of composite CR/CRi was 70.5% in the frontline setting, with median duration of response (DoR) of 8.3 months and overall survival (OS) of 7.1 months. In R/R AML, the CR/CRi rate was 64.7%, median DoR 10.5 months and median OS 9.8 months. Four out of the 43 patients who achieved CR/CRi (9.3%) following frontline treatment and 9 of the 22 R/R (40.9%) patients proceeded to allogeneic stem cell transplant (alloSCT) post induction. The median survival for all patients who underwent alloSCT is not reached in this analysis. The highest CR/CRi rates were observed in intermediate risk patients (90.9% in frontline treatment, 71.4% in R/R), with lower rates in both favourable (80% and 66.7%) and adverse risk patients (65.1% and 59.1% respectively). The presence of NPM1 and IDH1/2 mutations were associated with high CR/CRi rates in both the frontline (85.7% and 84.6% respectively) and R/R groups (100% and 81.8%), with below average response rates seen in TP53 mutated AML (62% in frontline, 40% in R/R). Notable responses were seen in patients with RUNX1 mutations in both settings (77.8% frontline, 66.6% R/R). Summary/Conclusion: Our data describes real world effectiveness for venetoclax combinations as both frontline and salvage therapy in UK clinical practice, similar to that seen in clinical trials. This further contributes to our understanding of these therapies, in particular their use as a viable treatment option in R/R patients and as a bridge to alloSCT, and highlights the importance of further characterisation of genetic predictors of response to inform treatment decisions in real-world practice.
ABSTRACT
Background : Coronavirus disease 19 (COVID-19) is associated with an increased risk of venous thromboembolism (VTE). Aims : To assess the effectiveness of outpatient thromboprophylaxis in patients with COVID-19. Methods : Consecutive patients hospitalized for SARS from March to May, 2020 were selected. Descriptive statistics, chi-square and t -tests were used to compare COVID-19 and non-COVID-19 patients. Results : The Newcastle upon Tyne Hospital NHS Foundation Trust is a large UK-based teaching hospital. All individuals admitted with COVID-19 were offered outpatient thromboprophylaxis (rivaroxaban 10 mg daily for 28 days) on discharge. Electronic medical records were reviewed for all admissions between 1st April and 15th May 2020, and for up to six months following discharge. Thromboprophylaxis was offered to those not at increased bleeding risk (see Figure 1). The study compares two groups, those individuals who received outpatient thromboprophylaxis (thromboprophylaxis) and those who did not (no thromboprophylaxis). Statistical analysis was performed using Fisher's exact test for categorical data and unpaired t test for continuous data. Data were collected from 179 medical inpatients with COVID-19, of these, 98 were eligible for thromboprophylaxis (Figure 1). The thromboprophylaxis group included 57 (58%) individuals and the no thromboprophylaxis 41 (42%). All medical records were reviewed at 3 and 6 months but all VTE and bleeding events occurred within the 3 months following discharge (see Figure 2). At 3-month follow up there was no difference in the rate of VTE events between the groups (thromboprophylaxis, 1;no thromboprophylaxis, 1;P = 1.00). All VTE events occurred between stopping thromboprophylaxis (at 28 days) and before the 3-month point. The use of thromboprophylaxis was not associated with an increased risk of major bleeding (thromboprophylaxis, 1;no thromboprophylaxis, 0;P = 1.00). The single bleeding event in the thromboprophylaxis group was an intracranial bleed following trauma and occurred two months after stopping the thromboprophylaxis. Conclusions : Extended thromboprophylaxis was not associated with an increased risk of major bleeding. No VTE events occurred whilst an individual was taking thromboprophylaxis. Further work is needed to investigate the optimum duration of thromboprophylaxis.
ABSTRACT
Background : COVID-19 is associated with a higher risk of venous thromboembolism (VTE). There is no consensus on the optimum dose of thromboprophylaxis. Aims : To assess the effectiveness of weight-based thromboprophylaxis dosing. Methods : This is a retrospective cohort study of all medical patients at a large UK-based teaching hospital, between April 1st and 15th May 2020. Electronic medical records were reviewed. People who were PCR positive for SARS-CoV-2 (COVID-19 positive) received a weight-based thromboprophylactic dose of enoxaparin (Table 1). Those PCR negative for SARS-CoV-2 (COVID-19 negative) received a standard dose (enoxaparin 40 mg daily). Chi square and Fisher's exact test were used for categorical variables, unpaired t test for continuous. Results : 569 cases (179 COVID-19 positive, 390 COVID-19 negative) were identified. The COVID-19 positive group had a significantly higher average age, a similar proportion of males and a greater average weight (Table 2). 86% of the COVID-19 positive group received the correct thromboprophylaxis dose for their weight. Most receiving an incorrect dose weighed >100 kg (54%) and received a lower dose than recommended. The incidence of new VTE was similar in the COVID-19 positive group (12, 7%) compared to those in the COVID-19 negative (16, 4%, P = 0.18). Most VTE events were proven radiologically apart from two COVID-19 positive patients diagnosed by clinical suspicion alone. Eight cases (67%) of VTE in patients with COVID-19 were pulmonary thrombosis, compared to twelve (75%) in patients without ( P = 0.69). Two cases of VTE occurred in the COVID-19 positive group whilst they were therapeutically anticoagulated compared to none in the COVID-19 negative group. Two major bleeding episodes occurred in the COVID-19 positive group and one in the COVID-19 negative ( P = 0.23). Conclusions : There was a similar incidence of VTE in medical patients with COVID-19 compared to those without. Weight-based thromboprophylaxis was not associated with an increased rate of bleeding.