Final Induction Therapy Results of an Open Label Phase II Study Using Inotuzumab Ozogamicin for Induction Therapy, Followed By a Conventional Chemotherapy Based Consolidation and Maintenance Therapy in Patients Aged 56 Years and Older with Acute B-Lymphoblastic Leukemia (INITIAL-1 trial)

Introduction: Acute lymphoblastic leukemia (ALL) represents approx. 5% of all newly diagnosed leukemias in patients between 55 and 70 years of age. Despite recent advances especially in younger patients, the prognosis of elderly patients with ALL remains dismal, even after moderately intensive chemotherapy. Incorporation of antibody-based therapies in the first line induction therapy bears the potential of a significant increased response rate and survival with the reduction of treatment toxicity. Methods: This open label phase II study of the German Multicenter Study Group on Adult Acute Lymphoblastic Leukemia was conducted at 13 centers. Patients aged >55 years with newly diagnosed Ph/BCR-ABL negative acute B-precursor ALL were eligible. Leukemic blasts had CD22 surface expression of at least 20%. The 1st induction cycle consisted of InO 0.8mg/m2 on day1 and 0.5mg/m2 on d8 and d15 together with dexamethasone 10 mg/m2 (day7-8, day14-17) and one intrathecal injection (i.th.) of methotrexate (MTX), cytarabine (AraC) and dexamethasone (Dex). The 2nd and 3rd induction cycle consisted of InO 0.5mg/m2 on day 1, 8 and 15 plus i.th. MTX/AraC/Dex. Patients achieving a complete remission (CR) were offered to receive 5 conventional consolidation therapies (3 x ID-MTX/asparaginase; 2 x ID-AraC) and one reinduction therapy (idarubicine/ AraC/ cyclophosphamide / Dex.) in combination with rituximab (for CD20+ ALL), followed by a maintenance therapy with 6-MP/MTX. The primary endpoint was event free survival (EFS) at 12-months follow-up. An event was defined as any of the following: persisting bone marrow blasts after 2 cycles of InO, relapse or death. An event rate of ≤40% at 12 months follow-up was considered to qualify the experimental treatment as very promising for additional testing. Under the assumption of one-sided type I error of 5% and 80% power, 42 evaluable patients were needed for primary endpoint analysis (registered with ClinicalTrials.gov, identifier: NCT03460522). Results: As of July 2021, 45 patients were included, with induction results available for 43 patients. Two patients were excluded per protocol from further analysis, as they received only one induction: 1 prolonged toxicity (CR after induction), 1 withdrawn consent. Median age at initial diagnosis was 64 years (range 56-80 years). 38 patients were diagnosed with a common- and 5 with a pro-B ALL. Median CD22 expression on leukemic blasts was 69% (range 21-99%). Due to suspected therapy related liver toxicities, a single patient received only 2 induction cycles (complete remission after 1st induction). All other patients completed 3 cycles of induction therapy and achieved complete remission (CR/CRi), mainly after the 1st induction. Results of minimal residual disease (MRD), measured by real-time quantitative PCR, are available for all 43 patients, with 23/43 (53%) and 31/42 (74%) patients being MRD negative after 2nd and 3rd induction therapy, respectively. Four patients with MRD failure (≥10 -4) after the 3rd induction therapy are still in CR (2 were treated with conventional chemotherapy per this protocol, one proceeded to allogeneic stem cell transplantation (aSCT), one received blinatumomab). MRD below the threshold of 10 -4 was detected in 15 patients after the 2nd induction (no relapse occurred so far). 8 of these 15 patients were MRD negative after the 3rd induction. So far, 7 events have been reported (during year 1: 3 deaths in CR and 1 relapsed ALL; during year 2: 1 death in CR and 2 patients with relapse). With a median follow-up of 422 days, the probability of OS at 1 and 2 years is 91% (95% C.I. 80-100%) and 77% (95% C.I. 57-96%), respectively. 4 patients received an aSCT in 1st CR, 1 patient in 2nd CR. Regarding adverse events (AEs) during induction cycles 1, 2 and 3, most common AEs ≥CTC grade 3 reported were leukocytopenia (in 60%, 12% and 3% of all cases, respectively), anemia (28%, 2%, 0%), thrombocytopenia (35%, 7%, 3%) and elevation of liver enzymes (14%, 5%, 0%). So far, one patient has been reported with suspected veno occlusive disease (after 2nd induction therapy). Conclusion: Three cycles of InO as induction therapy for the treatment of elderly patients with acute B-cell ALL results in very high remission rates with MRD-response in up to 90% (MRD negativity or MRD-levels <10 -4). The promising EFS and survival rates of these patients warrant further investigation of this novel induction therapy in a prospective randomized trial. Figure 1 Figure 1. Disclosures Stelljes: Pfizer: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Medac: Speakers Bureau; MSD: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Celgene/BMS: Consultancy, Speakers Bureau; Kite/Gilead: Consultancy, Speakers Bureau. Wäsch: Sanofi: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Pfizer: Consultancy; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Novartis: Consultancy; BMS/Celgene: Consultancy; Gilead: Consultancy. Nachtkamp: Jazz: Honoraria; Bsh medical: Honoraria; Celgene: Other: Travel Support. Haenel: Jazz: Consultancy, Honoraria; GSK: Consultancy; Bayer Vital: Honoraria; Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy; Celgene: Consultancy, Honoraria. Berdel: Philogen S.p.A.: Consultancy, Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees. Goekbuget: Amgen: Consultancy, Other: Invited talks for company sponsored symposia (with honoraria); Research funding for institution; Astra Zeneca: Other: Invited talk for company sponsored symposia (with honor); Erytech: Consultancy; Cellestia: Consultancy; Incyte: Other: Research funding for Institution; Jazz Pharmaceuticals: Other: Research funding for institution; Novartis: Consultancy, Other: Research funding for Institution; Gilead/Kite: Consultancy; Morphosys: Consultancy; Pfizer: Consultancy, Other: Research funding for institution; Servier: Consultancy, Other; Abbvie: Other. OffLabel Disclosure: Inotuzumab Ozogamicin

Prompt CR Plus Consolidation Therapy Yields Improve Survival after Allogeneic Transplantation for AML Patients Receiving Myeloablative, but Not Reduced-Intensity Conditioning: A CIBMTR Analysis

Leukemia relapse and treatment related mortality (TRM) remain major obstacles for successful allogeneic hematopoietic cell transplantation (allo-HCT). The number of induction cycles using intensive chemotherapy at AML diagnosis to achieve complete remission (CR) and the number of consolidation cycles and disease status at the time of allo-HCT for patients with acute myeloid leukemia (AML) may each affect TRM and relapse rates. We investigated the impact of the number of induction/consolidation cycles and disease status on the success of allo-HCT in 3113 AML patients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) (2008-2019). They received allo-HCT in first CR or with persistent leukemia (primary induction failure-PIF) receiving myeloablative (MA) or reduced-intensity (RIC) conditioning. 1473 AML patients (median age, 47 years) in CR received MAC; 862 (58%) achieved CR after 1 cycle of intensive induction chemotherapy and 74% of these had no evidence of measurable residual disease (MRD). 454 (31%) patients required 2 cycles to CR (72 % MRD negative) and 157 (11%) patients (69% MRD negative) after ≥ 3 cycles. The overall survival (OS), relapse and TRM by induction cycle number is shown in Table 1. Multivariate analysis demonstrated that CR after 1 cycle led to higher OS vs. 2 cycles (HR 1.32 95%CI 1.11-1.56, p< 0.01) or ≥ 3 cycles (HR 1.47 95%CI 1.16-1.87, p< 0.01), while OS after 2 cycles or ≥ 3 cycles were similar (HR 1.2 95%CI 0.87-1.4, p=0.38). Higher TRM was observed in patients receiving 2 or ≥ 3 cycles vs. only 1 induction cycles (HR 1.34 95%CI 1.05-1.72, p< 0.02). Relapse risk was greater in those needing ≥ 3 cycles to achieve CR. Consolidation therapy after CR was associated with improved OS vs. no consolidation therapy (HR 1.57 95%CI 1.24-1.99, p< 0.01). The need for ≥2 induction cycles plus consolidation therapy was associated with higher TRM (HR 1.34 95%CI 1.05-1.72, p< 0.02). 1162 AML patients (median age, 63 years) in CR received allo-HCT after RIC; 714 (61%) achieved CR after 1 cycle of induction chemotherapy (72% MRD negative); 310 (27%) patients after 2 cycles (67% MRD negative) and 138 (12%) patients (58% MRD negative) after ≥ 3 cycles (Table 1). Multivariate analysis demonstrated that the number of induction cycles did not affect the OS or TRM. Relapse risk was greater in patients requiring ≥2 cycles to achieve CR. The use of consolidation therapy did not affect OS or TRM. MRD status at the time of allo-HCT did not have a significant impact on OS, TRM and relapse rates after either MA or RIC conditioning. 478 AML patients received allo-HCT after PIF (328 patients with MAC [median age, 51 years], 150 patients RIC [median age, 61 years], Table 1). After MAC, OS and relapse were significantly worse in PIF patients compared to any CR patients (p<0.01). After RIC, relapse was significantly more frequent in PIF patients vs. CR patients after 1 or more induction cycles (p<0.01). TRM was similar for PIF vs CR patients after MAC or RIC allo-HCT. These data demonstrate that among patients eligible for allo-HCT, the need for only one induction cycle to achieve CR, particularly when combined with consolidation therapy is associated with better outcomes after MA conditioning. Achieving CR prior to allo-HCT needing one or more induction cycles is associated with lower relapse rates and improved OS compared to patients with PIF that receive allo-HCT. Figure 1 Figure 1. Disclosures de Lima: BMS: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Miltenyi Biotec: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees. Hourigan: Govt. COI: Other. Litzow: Omeros: Other: Advisory Board; Pluristem: Research Funding; Jazz: Other: Advisory Board; AbbVie: Research Funding; Amgen: Research Funding; Actinium: Research Funding; Astellas: Research Funding; Biosight: Other: Data monitoring committee. Saber: Govt. COI: Other. Weisdorf: Incyte: Research Funding; Fate Therapeutics: Research Funding.

Successful Treatment of Acute Myeloid Leukemia with CPX-351 in 2 Patients in the United Kingdom during the COVID-19 Pandemic

Introduction: The COVID-19 pandemic hit the United Kingdom in early 2020. High infection rates prompted concern for immunocompromised patients, including patients with AML receiving intensive chemotherapy. CPX-351 (Europe: Vyxeos ® Liposomal; US: Vyxeos ®), a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, is approved for the treatment of newly diagnosed therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in adults in Europe and in adults and pediatric patients aged ≥1 year in the United States. Despite concerns about intensive chemotherapy-related myelosuppression, the National Cancer Research Institute AML Working Group recommends that CPX-351 should continue to be administered in patients with adverse-risk cytogenetics and/or secondary AML during the pandemic. We report 2 patients with AML who were successfully treated with CPX-351 in the United Kingdom during the COVID-19 pandemic. Methods: The patients were diagnosed and managed per institutional guidelines. Two patients received CPX-351 induction (daunorubicin 44 mg/m 2 + cytarabine 100 mg/m 2) on Days 1, 3, and 5 (Days 1 and 3 for second induction) and CPX-351 consolidation (daunorubicin 29 mg/m 2 + cytarabine 65 mg/m 2) on Days 1 and 3, all by 90-minute IV infusion, during the pandemic. Results: The first patient was a 67-year-old male who presented with generalized fatigue in June 2020 with comorbidities of type 2 diabetes, diabetic nephropathy, and leg ulcers. Blood counts demonstrated a hemoglobin count of 79 g/L, white blood cell count of 0.7×10 9, platelet count of 58×10 9/L, and neutrophil count of 0.2×10 9/L. A bone marrow biopsy revealed AML-MRC with 40% blasts, and the patient had wild-type FLT3, NPM1, and SRSF2. The patient achieved morphologic and cytogenetic remission after 2 CPX-351 induction cycles. The patient then received 1 CPX-351 consolidation cycle but was not a candidate for transplant due to diabetic nephropathy. Tolerability improved with each cycle; the patient experienced neutropenic sepsis during the first induction, a flare up of leg ulcers and cellulitis during the second induction, and no tolerability concerns during the consolidation cycle. After the first induction, recovery of neutrophils and platelets occurred around Day 35 and Day 28, respectively (Figure 1), and counts recovered more quickly with each cycle. This patient was managed without contracting COVID-19 or experiencing any pandemic-related complications. The second patient was a 69-year-old female who presented with pancytopenia in February 2020 with no significant past medical or drug history. Her hemoglobin count was 66 g/L, white blood cell count was 0.6×10 9/L, platelet count was 17×10 9/L, and neutrophil count was 0.3×10 9/L. The patient was diagnosed with AML-MRC with mutated NPM1, SRSF2, IDH2, and JA2. During the first CPX-351 induction cycle, the patient contracted COVID-19. Some symptoms were present, but the patient did not become significantly unwell from COVID-19. Despite count recovery, the patient remained positive by nasal/oral PCR swab test for several weeks, delaying the delivery of the second CPX-351 induction cycle. After the second CPX-351 cycle began, the patient once again became positive for COVID-19 by PCR swab. The patient remained positive for longer than the first infection but was largely asymptomatic during the cycle (apart from a bout of sepsis). After a period of approximately 3 months from the previous CPX-351 cycle, the patient received a CPX-351 consolidation cycle and achieved complete remission with no measurable residual disease by NPM1 mutation in the bone marrow (Figure 2). The patient was eligible for transplant but declined. Conclusions: Two patients with AML-MRC were successfully treated with CPX-351 during the COVID-19 pandemic, despite one of the patients contracting and variably testing positive for the disease. During the pandemic, it is important to weigh the benefits of treating AML with curative intent versus the risks of immunosuppression and potential COVID-19 infection. Individualized decisions must be made for each patient based on disease, treatment, and COVID-19 risk factors through discussion with a multidisciplinary team. Although treating patients with AML with CPX-351 during the pandemic can be challenging, it remains an option for appropriate patients with newly diagnosed t-AML or AML-MRC. Figure 1 Figure 1. Disclosures Munisamy: Roche: Speakers Bureau; Jazz Pharmaceuticals: Speakers Bureau. Choudhuri: AstraZeneca, Bristol-Myers Squibb, Jazz Pharmaceuticals, and Pfizer: Consultancy.

CPX 351 As First Line Treatment in Higher Risk MDS. a Phase II Trial By the GFM

Background and aims: intensive chemotherapy (IC) has been used since the early 90's in the treatment of higher risk MDS, yielding 40 to 50% complete response (CR) but prolonged myelosuppression and 10 to 30% early deaths. IC is also recommended before allogeneic (allo) SCT when marrow blasts are increased (De Witte et al, Blood, 2017). CPX-351, a liposomal combination of cytarabine and daunorubicin, proved greater efficacy than classical IC with 3+7 in secondary-AML, including in patients with 20-30% marrow blasts and those who subsequently received allo SCT (Lancet et al, Lancet Haematol, 2021). We evaluated response to CPX-351 in a group of untreated higher risk MDS patients, most of whom were candidates for allo SCT. Methods: This prospective study, involving 12 GFM centers, included int-2 or high IPSS MDS, previously untreated with HMA or chemotherapy, and aged <70 years. CPX-351 induction treatment was given at 44mg/m 2 (DNR)/ 100mg/m 2 (CYT)/ day on days 1, 3 and 5. A second induction cycle (same daily dose, days 1 and 3 only) was allowed in patients who failed to achieve at least partial response (PR) according to IWG 2006. Consolidation cycles (same daily dose for one day) were planned (4 cycles) in responders. Allo SCT could follow after 1 to 4 consolidation cycles. Response to induction treatment, evaluated per protocol between day 28 and day 42, often had to be delayed due to prolonged cytopenia. For response evaluation, ELN 2017 criteria for AML were used in addition to IWG 2006 criteria for MDS, as the latter often proved difficult to interpret in the presence of persisting moderate cytopenia (especially the requirement of a Hb level ≥ 11 g/dl for CR definition). Results: 31 patients were included between July 2020 and January 2021. Median age was 62 years (range 31-69); WHO classification: 26 MDS-EB2, 5 CMML-2; IPSS: int-2: 84%, high: 16%; R-IPSS: intermediate: 29%, high: 55%, very high: 16%; karyotype: 2 very good, 22 good, 3 intermediate, 2 poor, 2 very poor. 27 patients received one induction cycle and 4 (in stable disease (SD) after the first cycle), a second induction cycle. Response rates, eventually evaluated a median of 53 days (range 28-112) from onset of induction, were with ELN 2017 criteria: CR: 52%, CRi: 13%, MLFS: 23%, SD: 13% and with IWG 2006 criteria : CR: 23%, mCR: 45%, mCR + HI-P: 6%, mCR + HI-P + HI-N: 6%, mCR + HI-N: 3%, PR: 3%, SD: 13%. Minimal residual disease assessment by NGS and flow cytometry will be presented at the meeting. 24/27 patients with baseline marrow blasts >10%, reached <5% blasts after induction treatment (figure 1). Median time to platelets >20G/L and >50G/L were: 16 (range 0-55) days and 28 (range 8-51), respectively and to ANC >1G/L: 26 (range 2-60) days. Only one patient had grade ≥ 3 mucositis and 4 had grade ≥ 2 alopecia during induction treatment. No patient died during induction treatment or required management in the intensive care unit. With a median follow-up of 201 days (range 102-350), 22 of the 30 patients initially considered for allo SCT received transplant after no (10 pts), 1 (9 pts), 2 or 3 (3 pts) consolidation cycles and 5 are planned for allo SCT. Reasons for not being transplanted were, investigators' choice (n=1), relapse (1), no donor (1) and invasive fungal infection (n=1). None of the 4 non transplanted patients received consolidation cycles. Reasons for not receiving consolidation cycles were persistent cytopenia (n=5), cardiac toxicity (n=2), failure to achieve CR or PR (n=2). At the time of analysis (June 2021), 4 patients had relapsed, after 3 to 6 months of response. Conclusions : CPX-351 is effective in higher risk MDS/CMML, especially to achieve blast clearance, and as a bridge to allo SCT. Figure 1: waterfall plot according to IWG 2006 and ELN 2017 criteria Figure 1 Figure 1. Disclosures Fenaux: Novartis: Honoraria, Research Funding; Syros Pharmaceuticals: Honoraria; Takeda: Honoraria, Research Funding; JAZZ: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene/BMS: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding. OffLabel Disclosure: CPX-351 use off-label for myelodysplastic syndroms in a prospective trial

Assessing treatment response after intravesical bacillus Calmette–Guerin induction cycle: are routine bladder biopsies necessary?

Purpose To determine the need for routine bladder biopsies (BBs) in assessing response to the induction cycle of intravesical bacillus Calmette–Guérin (BCG) for high-risk non-muscle-invasive bladder cancer (NMIBC). Methods Our prospectively maintained NMIBC database was queried to identify patients with high-risk disease (carcinoma in situ, high-grade Ta/T1) who underwent BBs after BCG induction cycle. Urine cytology, cystoscopy, and BBs findings were evaluated. Results A total of 219 patients met the inclusion criteria. Urine cytology was positive in 20 patients and negative in 199; cystoscopy was positive in 35 patients, suspicious in 32 and normal in 152 patients. BBs yielded bladder cancer (BCa) in 43 (19.6%) patients, with a BCa rate of 9.3% in patients with negative cytology and cystoscopy as opposed to 38.0% in patients whereby one or both exams were suspicious/positive. The diagnostic accuracy of urine cytology, cystoscopy, and combined tests was 0.56, 0.70, and 0.71, respectively. The negative predictive value of combined tests was 90.7%. Performing BBs only in patients with positive cytology and/or positive/suspicious cystoscopy would have spared 140 (64%) patients to undergo this procedure while missing BCa in 13 (9.3%) of them, representing 30% of all BCa cases. Conclusion Performing BBs only in patients with positive cytology and suspicious/positive cystoscopy would spare 64% of un-necessary BBs but miss a non-negligible number of BCas. While no data are available regarding the potential consequences of missing such BCas, such information should be taken into account in patient’s counselling.

Effects of lenalidomide on the bone marrow microenvironment in acute myeloid leukemia: Translational analysis of the HOVON103 AML/SAKK30/10 Swiss trial cohort

This translational study aimed at gaining insight into the effects of lenalidomide in acute myeloid leukemia (AML). Forty-one AML patients aged 66 or older of the Swiss cohort of the HOVON-103 AML/SAKK30/10 study were included. After randomization, they received standard induction chemotherapy with or without lenalidomide. Bone marrow biopsies at diagnosis and before the 2nd induction cycle were obtained to assess the therapeutic impact on leukemic blasts and microenvironment. Increased bone marrow angiogenesis, as assessed by microvessel density (MVD), was found at AML diagnosis and differed significantly between the WHO categories. Morphological analysis revealed a higher initial MVD in AML with myelodysplasia-related changes (AML-MRC) and a more substantial decrease of microvascularization after lenalidomide exposure. A slight increase of T-bet-positive TH1-equivalents was identifiable under lenalidomide. In the subgroup of patients with AML-MRC, the progression-free survival differed between the two treatment regimens, showing a potential but not significant benefit of lenalidomide. We found no correlation between the cereblon genotype (the target of lenalidomide) and treatment response or prognosis. In conclusion, addition of lenalidomide may be beneficial to elderly patients suffering from AML-MRC, where it leads to a reduction of microvascularization and, probably, to an intensified specific T cell-driven anti-leukemic response.

Multiple spontaneous coronary artery dissections associated with intravenous daunorubicin treatment for acute myelocytic leukaemia: a case report

Background Multiple spontaneous coronary artery dissection (SCAD) is a rare condition which may lead to serious consequences such as sudden cardiac death, acute myocardial infarction (AMI), and acute heart failure. Case summary In this paper, we report the case of a 57-year-old woman with acute myelocytic leukaemia who was undergoing her second phase of chemotherapy. After the first induction cycle of intravenous infusion of daunorubicin, the patient experienced chest pain, shortness of breath, and low blood pressure. The electrocardiograms revealed significant ST-elevation in the D1, aVL, and V2–V6 leads, which indicated AMI. Coronary catheterization showed spontaneous coronary dissection in the mid-left descending coronary artery and first obtuse marginal artery of the circumflex. The patient died immediately. Discussion This is the first reported case of multiple SCAD associated with intravenous (IV) daunorubicin infusion. We also reviewed the literature and proposed the mechanism of this complication.

Remission and Survival after Single Versus Double Induction with 7+3 for Newly Diagnosed Acute Myeloid Leukemia: Results from the Planned Interim Analysis of Randomized Controlled SAL-Daunodouble Trial

Background Double induction using two subsequent 7+3 regimens of cytarabine plus anthracycline is commonly performed in AML patients with an adequate performance status in order to maximize dose intensity upfront. However, for patients with a good early response at day 15 of first induction, there is no prospective randomized evidence on the necessity or value of a second induction cycle. Aims In order to answer the question if good responders of the first 7+3 induction could be spared a second induction cycle, we set up randomized-controlled SAL DaunoDouble trial. The study prospectively assesses the outcome of patients with a good early response with respect to the number of induction cycles (single versus double). We assumed non-inferiority of single induction in terms of complete remission (CR/CRi) rate, based on a margin of 7.5%. Here, we present the results of the planned interim analysis. Methods Patients (pts) 18-65 years with newly diagnosed AML, normal cardiac and organ function received a first induction cycle with seven days of cytarabine plus three days of daunorubicin ("7+3"). Response assessment in bone marrow was done on day 15 after the initiation of chemotherapy and confirmed by central review. A blast count <5% was defined as good response. Pts with good response were randomized to receive a second induction cycle (arm D) or no second induction cycle (arm S). Primary endpoint was CR/CRi after completion of induction, secondary endpoints were RFS, and OS. Results Between 2014 and 2020, 624 evaluable pts were enrolled and received the first induction cycle with 7+3. A marrow blast clearance below 5% on day 15 was achieved in 298 pts (48%), providing eligibility for randomization. Of these patients, 150 were randomized into arm S and 148 into arm D, respectively. Median age was 52 years, 92% had de novo AML, NPM1 mutation was present in 53%, FLT3-ITD in 25% of pts. Favorable, intermediate and adverse risk (ELN 2017) were present in 56%, 34% and 10% of pts, respectively. CR/CRi rates at the end of induction were 86% after single induction and 85% after double induction. The CR/CRi rates in 224 pre-defined per-protocol pts were 88% versus 91%, resulting in a CR difference of 3% (95%-CI -0.047-0.111; p for non-inferiority test 0.145). After a median follow-up time of 24 months, RFS was slightly but not significantly lower after single induction with a 3-year RFS of 53% versus 64% (HR 1.4, p=0.125), whereas no differences were seen in 3-year OS, with a of rate of 74% versus 75% (HR 1.1, p=0.645) after single versus double induction. Conclusion The interim analysis results show that in good responders, the difference between CR rates after single versus double induction was even smaller than the predefined 7.5% margin, suggesting a trend for non-inferiority of single induction, although statistical significance was not reached. The trial continued recruitment. These findings suggest that in good responders, it may be safe to omit a second induction cycle if a second cycle poses a high risk. Figure. CR + CRi, RFS and OS after randomization to single versus double induction. Disclosures Alakel: Pfizer: Consultancy. Jost:Pfizer: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; JAZZ: Other: travel support; Celgene: Other: travel support. Novak:Roche: Consultancy; Janssen: Other: Travel expenses; Takeda: Consultancy; Amgen: Consultancy, Other: Travel expenses; Pfizer: Consultancy; Novartis: Consultancy. Krause:Takeda: Honoraria; Celgene: Other: Travel Support; MSD: Honoraria; Pfizer: Honoraria; Siemens: Research Funding; Gilead: Other: Travel Support. Held:Roche: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; BMS: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; MSD: Consultancy; Acrotech: Research Funding; Spectrum: Research Funding; Amgen: Research Funding. Platzbecker:AbbVie: Consultancy, Honoraria; Amgen: Honoraria, Research Funding; Geron: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria. Thiede:AgenDix GmbH: Other: Co-owner and CEO. Müller-Tidow:Daiichi Sankyo: Research Funding; Pfizer: Research Funding, Speakers Bureau; BiolineRx: Research Funding; Janssen-Cilag GmbH: Speakers Bureau.