Chronic myeloid leukaemia (CML) has been classically described as a disease restricted to the bone marrow with very few reports of extramedullary involvement. CNS involvement with CML has been described in the literature as an aggressive disease in the leukaemic phase either preceding or coexisting with medullary blast crisis or seen in patients with long-term Imatinib therapy. No treatment consensus exists for this patient group and outcomes remain poor. We hereby present a very rare report of CNS involvement with chronic phase CML at diagnosis in a patient who presented with raised intracranial pressure and cranial nerve palsies.

INTRODUCTION: Standard 1st line therapeutic strategies for patients (pts) with newly diagnosed (ND) acute myeloid leukaemia (AML) include intensive chemotherapy (IC). However, the incidence of AML increases with age and many pts are ineligible for IC due to comorbidities and/or poor performance status. In these pts efficacy and safety of venetoclax (VEN)-based combinations with azacitidine (AZA) or low dose cytarabine (LDAC) has been demonstrated in clinical trials, with subsequent approval granted by the UK Medicines and Healthcare Regulatory Agency (MHRA). it is vital to understand the outcomes and treatment patterns of patients managed in the real world (RW) setting. This study aimed to examine real world clinical effectiveness and management of VEN+AZA/LDAC in ND AML pts ineligible for IC in Great Britain (GB). METHODS: 9 centres in England and Wales identified 167 adult pts with ND AML initiated on VEN+HMA/LDAC on or after the date of MHRA approval (28th May 2021/25th February 2022 respectively). Data collection ended 8th May 2024. Eligible pts must have been initiated on VEN therapy at least 28 days prior to data collection, not received VEN as part of a clinical trial and not have history of other malignancies within 2 years prior to VEN. Clinical characteristics, treatment patterns and clinical outcomes were captured in a retrospective chart review. Outcomes measured included overall survival (OS), event-free survival (EFS), composite complete remission (CRc), complete remission with partial haematologic recovery (CRh) and complete remission with incomplete marrow recovery (CRi). RESULTS: The median (range) pt age was 75.6 (53.6, 86.3), with over half reported to be ≥75 (55.7%, n=93). Females made up 42% of the total sample (n=70). 66.3% (n=108) had de novo AML and 33.7% (n=55) had clinical secondary AML. AML type was unknown for 2.4% (n=4). Of patients with ECOG performance status (PS) data available (n=125), 76% (n=95), 18.4% (n=23) and 5.6% (n=7) had an ECOG PS of <1, 2 and 3 respectively. Over half of pts had adverse ELN 2017 genetic risk classification (58.7%, n=98). Mutational status was known in 97.6% (n=163), of which 87.7% (n=143) had at least 1 genetic mutation present. Common mutations observed included IDH1/IDH2 (23.3%, n=38), TP53 (17.8%, n=29), NPM1 (11.0%, n=18), and FLT3 ITD (9.8%, n=16). Treatment initiation was mostly performed in the inpatient setting (89.0%, n=149), with the vast majority receiving VEN+AZA (97.6%, n=163), few pts receiving VEN+LDAC (2.4%, n=4). A VEN dose ramp up was used for most pts (86.8%, n=145). BM data was available for all pts. For pts with >1 BM assessment date available (n=138), the majority of first assessments post-VEN initiation were performed during cycle 1 (97.1%, n=134). 10.2%, (n=17) of patients had ≥1 in-cycle dose interruption. The median (range) number of days pts received VEN was 28 days (2,28) in cycle 1, 21 days (5,28) in cycle 2 and 14 days (5,28) in cycle 3 to cycle 6, respectively. Antifungals were prescribed in 86.6% (n=145) during cycle 1. 3.0% (n=5) proceeded to hematopoietic cell transplantation during their 1st line of therapy. Median (range) duration of follow-up was 7.4 months (0.1,30.5) and median (range) duration of treatment was 5.3 months (0.0,31.0). VEN treatment was discontinued in 47.9% (n=80). Among those who discontinued treatment, reasons for discontinuation included adverse events (28.8%, n=23), relapse (23.8%, n=19) and insufficient response/ refractory to treatment (17.5%, n=14). Median OS was 14.2 months (95% CI; 11.5;21.1) with 1-year OS 56.4%. Median EFS was 9.3 months (95% CI; 7.3;14.4) with 1-year EFS 44.0%. CRc was 70.7% (n=118), with CR 45.5% (n=76), CRh 6.0% (n=10) and CRi 19.1% (n=32). Among pts achieving CRc, median (range) time to response (TTR) was 1.1 months (0.1,12.4) and median duration of response (DoR) [95% CI] was 18 months (10.4; not estimable). CONCLUSION: Results from the GB AML ARC initiative support RW treatment effectiveness of VEN-based combinations in ND IC ineligible pts with high CRc, sustained DoR, meaningful OS and EFS outcomes. Most BM assessments were performed in cycle 1 in RW settings, highlighting the importance of early BM assessment. Outcomes reported here such as TTR, CRc, DoR and OS are similar to findings from Phase III VIALE-A trial. The results overall offer valuable insights on RW management, and associated clinical outcomes, in AML pts ineligible for IC treated with VEN-based regimens.

Molecular failure in NPM1-mutated acute myeloid leukemia (AML) inevitably progresses to frank relapse if untreated. Recently published small case series show that venetoclax combined with low -dose cytarabine or azacitidine can reduce or eliminate measurable residual disease (MRD). Here, we report on an international multicenter cohort of 79 patients treated for molecular failure with venetoclax combinations and report an overall molecular response (>= 1 -log reduction in MRD) in 66 patients (84%) and MRD negativity in 56 (71%). Eighteen of 79 patients (23%) required hospitalization, and no deaths were reported during treatment. Forty-one patients were bridged to allogeneic transplant with no further therapy, and 25 of 41 were MRD negative assessed by reverse transcription quantitative polymerase chain reaction before transplant. Overall survival (OS) for the whole cohort at 2 years was 67%, event -free survival (EFS) was 45%, and in responding patients, there was no difference in survival in those who received a transplant using time -dependent analysis. Presence of FLT3-ITD mutation was associated with a lower response rate (64 vs 91%; P < .01), worse OS (hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.06-5.86;P = .036), and EFS (HR, 1.87; 95% CI, 1.06-3.28; P = .03). Eighteen of 35 patients who did not undergo transplant became MRD negative and stopped treatment after a median of 10 months, with 2 -year molecular relapse free survival of 62% from the end of treatment. Venetoclax-based low intensive chemotherapy is a potentially effective treatment for molecular relapse in NPM1mutated AML, either as a bridge to transplant or as definitive therapy.

Advancements in comprehending myelodysplastic neoplasms (MDS) have unfolded significantly in recent years, elucidating a myriad of cellular and molecular underpinnings integral to disease progression. While molecular inclusions into prognostic models have substantively advanced risk stratification, recent revelations have emphasized the pivotal role of immune dysregulation within the bone marrow milieu during MDS evolution. Nonetheless, immunotherapy for MDS has not experienced breakthroughs seen in other malignancies, partly attributable to the absence of an immune classification that could stratify patients toward optimally targeted immunotherapeutic approaches. A pivotal obstacle to establishing "immune classes" among MDS patients is the absence of validated accepted immune panels suitable for routine application in clinical laboratories. In response, we formed International Integrative Innovative Immunology for MDS (i4MDS), a consortium of multidisciplinary experts, and created the following recommendations for standardized methodologies to monitor immune responses in MDS. A central goal of i4MDS is the development of an immune score that could be incorporated into current clinical risk stratification models. This position paper first consolidates current knowledge on MDS immunology. Subsequently, in collaboration with clinical and laboratory specialists, we introduce flow cytometry panels and cytokine assays, meticulously devised for clinical laboratories, aiming to monitor the immune status of MDS patients, evaluating both immune fitness and identifying potential immune "risk factors." By amalgamating this immunological characterization data and molecular data, we aim to enhance patient stratification, identify predictive markers for treatment responsiveness, and accelerate the development of systems immunology tools and innovative immunotherapies.

ABSTRACT:Assessment of measurable residual disease (MRD) by quantitative reverse transcription polymerase chain reaction is strongly prognostic in patients with NPM1-mutated acute myeloid leukemia (AML) treated with intensive chemotherapy; however, there are no data regarding its utility in venetoclax-based nonintensive therapy, despite high efficacy in this genotype. We analyzed the prognostic impact of NPM1 MRD in an international real-world cohort of 76 previously untreated patients with NPM1-mutated AML who achieved complete remission (CR)/CR with incomplete hematological recovery following treatment with venetoclax and hypomethylating agents (HMAs) or low-dose cytarabine (LDAC). A total of 44 patients (58%) achieved bone marrow (BM) MRD negativity, and a further 14 (18%) achieved a reduction of ≥4 log10 from baseline as their best response, with no difference between HMAs and LDAC. The cumulative rates of BM MRD negativity by the end of cycles 2, 4, and 6 were 25%, 47%, and 50%, respectively. Patients achieving BM MRD negativity by the end of cycle 4 had 2-year overall of 84% compared with 46% if MRD was positive. On multivariable analyses, MRD negativity was the strongest prognostic factor. A total of 22 patients electively stopped therapy in BM MRD-negative remission after a median of 8 cycles, with 2-year treatment-free remission of 88%. In patients with NPM1-mutated AML attaining remission with venetoclax combination therapies, NPM1 MRD provides valuable prognostic information.

Assessment of measurable residual disease (MRD) by RT-qPCR is strongly prognostic in patients with NPM1-mutated AML treated with intensive chemotherapy, however there are no data regarding its utility in venetoclax-based non-intensive therapy, despite high efficacy in this genotype. We analysed the prognostic impact of NPM1 MRD in an international real-world cohort of 76 previously untreated patients with NPM1-mutated AML who achieved CR/CRi following treatment with venetoclax and hypomethylating agents (HMA) or low dose cytarabine (LDAC). 44 patients (58%) achieved bone marrow (BM) MRD negativity and a further 14 (18%) a reduction of ≥4 log10 from baseline as their best response, with no difference between HMA and LDAC. The cumulative rate of BM MRD negativity by the end of cycles 2, 4 and 6 was 25%, 47% and 50%. Patients achieving BM MRD negativity by the end of cycle 4 had 2-year overall (OS) of 84% compared to 46% if MRD positive. On multivariable analyses MRD negativity was the strongest prognostic factor. 22 patients electively stopped therapy in BM MRD negative remission after a median of 8 cycles with 2-year treatment-free remission of 88%. In patients with NPM1-mutated AML attaining remission with venetoclax combination therapies, NPM1 MRD provides valuable prognostic information.

None of the authors have any conflicts of interest to declare.

Background Optimal treatment for patients with relapsed/refractory (R/R) acute myeloid leukemia (AML), particularly after molecular relapse or disease recurrence following allogeneic hematopoietic stem cell transplantation (HSCT), is undefined. Intensive salvage chemotherapy is frequently offered but is often ineffective and carries significant risk of toxicity, especially post-HSCT. Such toxicity is particularly undesirable in those patients with low burden disease, such as molecular relapse. While venetoclax (VEN, BCL-2 inhibitor) combined with FLAG-Ida was effective in a phase Ib/2 study of R/R AML (DiNardo, 2021), molecular relapse was not included, and only 14/68 subjects were treated at post-HSCT relapse. Concerns regarding toxicity of that regimen persist. Alternatively, VEN combined with hypomethylating agents or low dose cytarabine (HMA, LDAC) has shown clinical activity with good tolerability in relapsed AML, but only in small studies with little focus on outcomes following molecular or post-transplant relapse. Herein, we report outcomes after non-intensive VEN salvage combinations in a large population of patients with R/R AML treated in the UK. Methods The outcomes of adults with R/R AML receiving non-intensive VEN combinations as salvage therapy in UK hospitals were studied. Patients included had a diagnosis of AML/high risk myelodysplastic syndrome (MDS, ≥10% bone marrow blasts); refractory disease/relapse following ≥1 line of chemotherapy and at least 3 months follow up from initiation of VEN combined with non-intensive chemotherapy regimens. Response was defined by European Leukemia Net (ELN) criteria. Results 126 evaluable patients (117 AML, 9 high risk MDS) were treated during 2017-2022 (Table 1). The median age was 58 years (range 17-83 years). By ELN 2017 criteria, 32 AML patients were adverse risk, 39 intermediate and 42 favourable (4 unknown). Diagnostic analyses, where available, demonstrated mutations of NPM1 in 34 AML patients, IDH1/2 (n=17), tumour suppressor genes (n=12) and signalling pathway genes (n=37), predominantly FLT3 (n=21). 30 patients had primary refractory disease whilst 96 had relapsed (45 pre-HSCT, 51 post-HSCT). 19 patients had molecular measurable residual disease (MRD; 18 molecular relapse, 1 molecular persistence) whilst 103 had morphologic, flow cytometric or extramedullary disease (4 unknown). VEN was combined with HMA (n=75), LDAC (n=44) or used with other low intensity agents/as monotherapy (n=7). For the whole cohort, with a median follow up of 16.6 months, the median overall survival (OS) was 8.5 months (95% confidence interval [CI] 4.8-12.2 months), including when censored at subsequent transplant. 56 (44%) patients achieved CR/CRi; best response occurred after a median of 1 cycle (range 1-6). Those patients with ELN 2017 favourable risk disease experienced the best outcomes (median OS not reached vs 6.5 months [95% CI 4-9-8.2 months] for the remaining cohort; p <0.001). Median OS was inferior for both intermediate and adverse risk groups at 7.1 months (95% CI 4.5-9.7 months) and 5.8 months (95% CI 3.6-8.1 months), respectively. Notably, 16/19 (84%) patients treated for molecular MRD achieved molecular CR/CRi. This group experienced superior median OS compared with the 103 patients with morphologic/flow positive/extramedullary disease (18.4 months vs 7.1 months, 95% CI 4.9-9.3 months; p = 0.004), Figure 1. In total, 34 patients (27%) were successfully bridged to transplant after VEN salvage. Median OS from transplant not reached, despite follow up of 11.8 months, with similar outcomes regardless of whether disease was R/R when treated with VEN combinations (Figure 1). Of 51 patients treated for post-HSCT relapse, 21 (41%) achieved CR/CRi, 16 (31%) received donor lymphocyte infusions and 13 (25%) proceeded to second HSCT. Toxicity of non-intensive VEN combinations was consistent with previous reports: tumour lysis syndrome was reported in 6 (5%) patients and infection requiring antibiotics in 76 (60%). Conclusion These real-world data demonstrate that VEN-based non-intensive combinations are well tolerated and active in R/R AML, particularly in patients with molecular relapse, and represent an important route to potentially curative cellular therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Patients with secondary AML or MDS derived AML have poor outcomes compared to de-novo AML. The benefits of intensive chemotherapy without anticipated transplant consolidation have been previously doubted. Outcomes in USA trial centres have not often been closely replicable in real world settings. From November 2018 CPX-351 has been available in the UK for secondary AML, therapy related AML, AML with MDS related Karyotype (AML-MRC) and licensed but not funded for AML with myelodysplastic related changes.

An 87-year-old man who had been under urological follow-up with a raised prostate-specific antigen was referred to haematology with widespread infiltrative bone disease, sternal and vertebral fractures and a normocytic anaemia. He had a two-year history of bone pain, which had worsened in the previous two months. Serum protein electrophoresis revealed an immunoglobulin (Ig) A lambda paraprotein at too low a concentration to quantify. The patient also had immune paresis. The serum free kappa light chains were 3·9 mg/l (normal range 3·3–19·4) and lambda 3.55 mg/l (5·7–26·3). Haemoglobin concentration was 89 g/l, creatinine 128 µmol/l and corrected calcium 2·39 mmol/l. A bone marrow aspirate was haemodilute with no apparent excess of plasma cells seen, but flow cytometry identified 6·5% plasma cells, which were positive for CD38 and CD138 and negative for CD45, CD19 and CD27. Bone marrow trephine biopsy sections showed suppression of haematopoiesis with an interstitial infiltrate of elongated cells with spindle morphology, suggestive of neuroendocrine malignancy or perhaps a sarcoma, with no cytomorphological similarities to plasma cells (left, haematoxylin and eosin, ×40 objective). However, these cells were positive for CD138 (right, immunoperoxidase, ×20), MUM1 and IgA heavy chain, confirming that the spindle cells were neoplastic plasma cells and that the bony disease was due to multiple myeloma. Interestingly, the neoplastic plasma cells were strongly cyclin D1-positive and CD79a, kappa and lambda-negative, despite the low level IgA lambda paraprotein in the plasma. Given the age and frailty of the patient, he is being treated with lenalidomide and dexamethasone.

Abstract Background Early data suggest that patients undergoing salvage chemotherapy for relapsed or refractory (R/R) acute myeloid leukaemia (AML) have poor outcomes if infected with SARS-CoV-2, and nosocomial transmission has been a major problem worldwide. Gilteritinib is effective in R/R FLT3 mutated AML, is significantly less immunosuppressive and does not require hospital admission, however at the start of the pandemic this was not yet approved for routine use in all countries. In the United Kingdom, the National Health Service (NHS) made gilteritinib available as an emergency measure from late April 2020 to patients aged >16y with R/R FLT3 mutated AML, with the aim of reducing both mortality and healthcare resource use. We report a health-system-wide real world data collection for toxicity and patient outcomes across 27 NHS Hospitals. Methods Each patient was registered on a central NHS database, with clinicians certifying that their patient met the above criteria. Anonymised data were retrospectively collected by treating physicians. Gilteritinib 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 81 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 Fifty patients were included with a median age of 59y (range 19 - 77) and 50% male. The majority (83%) had an ECOG performance status of 0-1. AML was secondary to a previous haematological disorder in 12%, therapy-related in 4% and de novo in the remaining 84%. The disease was refractory to the last therapy in 38%. Most patients had previously received 1 (65%) or 2 (33%) lines of therapy, including intensive chemotherapy in a majority (86%). A FLT3 inhibitor had previously been administered to 45% and 35% were post allogeneic transplant. The FLT3 mutation was an internal tandem duplication (ITD) in 80% and tyrosine kinase domain (TKD) mutation in 22%. NPM1 mutations were detected in 34%. Next-generation sequencing results were available for 94% of patients, with mutations in IDH1 or IDH2 in 12.5%, ASXL1 in 2%, RUNX1 in 21% and no TP53 mutations. Patients spent a median 3.5 days in hospital in cycle 1, 0 days in cycles 2 and 3 and 1 day in cycle 4. In cycles 1, 2, 3 and 4, the median number of days of grade 4 neutropenia was 18, 7, 7.5, and 6.5 respectively, and the grade 4 thrombocytopenia was 2, 7, 0.5 and 0.5. The composite complete remission (CR) / CR with incomplete haematological recovery (CRi) rate was 27%. MRD data is being collected. The best response was morphological leukaemia free state (MLFS) in 4%, partial remission (PR) in 25% and refractory disease in 38%. The rate of combined CR/CRi did not differ in those with previous exposure to FLT3 inhibitors (23% vs 32%, p=0.6) or with past allogeneic transplant (29% vs 27%, p=0.3). There were no CR/CRi in patients with adverse cytogenetic risk. Median follow-up was 10.5 months (95%CI 7.3 - 12.3) with median overall survival (OS) 6.7 months (95%CI 4.5 - not reached). Mortality at day 30 was 0% and day 60 was 14%. 12-month overall survival was 38%. Patients who achieved a CR/CRi had a 12-month OS of 83%, and for PR this was 35%. Survival did not differ in those with previous FLT3 inhibitor exposure (HR 1.0, p>0.9) or allogeneic transplant (HR 0.63, p=0.3). Seven patients (14%) so far have been bridged with gilteritinib to allogeneic transplant. Conclusion Our data demonstrate that gilteritinib is well tolerated and clinically active in adults with relapsed FLT3 mutated AML. Importantly, during the COVID-19 pandemic, its availability has permitted the great majority of treatment to be delivered as an outpatient with significant resource saving at a time of critically constrained inpatient resources. Patients who achieve CR/CRi have good short-term outcomes and are able to proceed to a potentially curative allogeneic stem cell transplant. Figure 1 Figure 1. Disclosures Belsham: Celgene: Other: meeting attendance; Abbvie: Other: meeting attendance. Byrne: Incyte: Honoraria. 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: Amgen: Honoraria; Daichi Sankyo: Other: Travel Support; Janssen: Honoraria; Novartis: Other: Travel Support; Pfizer: Honoraria. Munisamy: Jazz Pharmaceuticals: Speakers Bureau; Roche: Speakers Bureau. Murthy: Abbvie: Other: support to attend educational conferences.. Smith: Daiichi Sankyo: Speakers Bureau; Pfizer: Speakers Bureau; ARIAD: Honoraria. Craddock: Novartis Pharmaceuticals: Other: Advisory Board ; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding. 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; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Research Support, Educational Events.

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 the 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. Figure 1 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.