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Background: Options to treat elderly patients with newly diagnosed AML include intensive, attenuated chemotherapy, hypomethylating agents (HMA) and supportive care (SC). HMA have proven their efficacy in DACO-016 (NCT00260832) and AML-001 (NCT01074047) clinical trials, with a median overall survival (OS) of 7.7 months (95%CI, 6.2 to 9.2) with decitabine (DEC) vs. 5.0 months (95%CI, 4.3 to 6.3) with therapy choice (TC), considered SC or low-dose Ara-C (LDAC). Median OS was 10.4 months with azacitidine (AZA) (95%CI, 8.0 to 12.7) vs. 6.5 months (95%CI, 5.0 to 8.6) with conventional care regimens (CCR), considered standard induction chemotherapy, LDAC or SC. However, there are few direct comparative data of AZA and DEC in the context of trials or real-life settings. Aims: Here, we compared clinical outcomes between AZA and DEC in AML patients not eligible for intensive chemotherapy in the epidemiologic PETHEMA registry. Methods: We included newly diagnosed AML patients treated with AZA (75 mg/m2/d IV or SC days 1-7) or DEC (20 mg/m2/d IV days 1-5) that were not eligible for intensive chemotherapy. Responses were recorded using IWG 2003 criteria. Rates of Complete Response (CR), complete response with incomplete recovery (CRi) and OS were co-primary endpoints. Results: Between 2006 and 2019, 638 patients were included. 497 (78%) received AZA and 141 (22%) received DEC as per physician judgement. Baseline characteristics were comparable in both groups (Table 1), except for bone marrow blasts count ≥ 30%, which was more frequent in DEC group (59.2% vs 77.1%, p<0.001). The CR rate was 16.3% vs 20.6% (p = 0.23); composite CR (CR+CRi) was 18.5% vs 22% (p = 0.35), and the overall response rate (ORR, partial remission (PR) plus CR+CRi) was 29.2% vs 34.8% (p=0.20); for AZA vs DEC, respectively. A significantly higher ORR to AZA was associated with ECOG <2 (33.9% vs. 12.4% in patients with ECOG ≥2, OR 0.22, 95% CI 0.10 - 0.49, p=0.000), de novo AML (35.3% vs. 21.9% in secondary AML; OR 0.38, 95% CI 0.20 - 0.71, p=0.002) and estimated glomerular filtrate rate ≥ 45 mL/min/1.73m2 (30.4% vs. 9.3% in patients with estimated glomerular filtrate rate ≥ 45 mL/min/1.73m2; OR 0.15, 95% CI 0.034 - 0.67, p=0.013); while bone marrow blast count < 50% was the only factor influencing ORR to DEC (43.7% vs. 25% in ≥ 50% bone marrow blasts, p=0.029). With a median follow up of 12 months, median OS was 10.0 (95% CI 8.7 - 11.2) vs 8.0 (5.7- 10.2) months for AZA vs DEC, respectively (p = 0.46) (Figure 1). Median OS was 21 (17.8 - 24.1) vs 16 (12.6 - 19.3) vs 6 months (5.0 - 7.0) for patients who achieved CR/CRi vs PR vs no response (p<0.001) (Figure 2). Additional subgroup analyses by baseline characteristics performed to compare AZA vs DEC revealed that patients ≥ 80 years did benefit for treatment with AZA, median OS of 8 vs. 4 m (p=0.042), as well as patients with WBC ≥ 10 x109/L (8 vs. 5 m, p=0.036), platelet count <20 x109/L (8 vs. 4 m, p=0.021) and those with estimated glomerular filtrate rate ≥ 45 mL/min/1.73m2 (10 vs. 5m, p=0.033). Conclusions: This is a large retrospective comparison with long-term follow-up of clinical outcomes associated with AZA and DEC treatment for patients with AML patients not eligible for intensive chemotherapy. There were no significant differences in ORR, CR/CRi or OS between AZA and DEC. However, patients with WBC ≥ 10 x109/L, platelet count <20 x109/L and estimated glomerular filtrate rate ≥ 45 mL/min/1.73m2 could benefit from AZA in terms of OS. Disclosures Tormo: Janssen: Honoraria; Daiichi Sankyo: Honoraria; Servier: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Honoraria. Ramos:Amgen: Consultancy, Other: travel grant ; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel grant , Research Funding; Novartis: Consultancy, Other: travel grant; Takeda: Consultancy, Other: travel grant ; Daiichi-Sankyo: Other: travel grant ; Merck-Sahrp & Dohme: Other: travel grant; Rovi: Other: travel grant; Roche: Other: travel grant ; Jannsen: Other: travel grant; Abbvie: Consultancy, Other: travel grant .

Introduction: Asciminib is a new BCR-ABL1 inhibitor that differs from previous tyrosine kinase inhibitors (TKIs) in that it does not bind to the ATP-binding site of the kinase. Data from different clinical trials has shown an adequate safety and efficacy profile in chronic myeloid leukemia (CML) patients failing previous TKIs. However, no findings have been communicated in real life experience. The aim of our study is to present first results of asciminib in CML patients failing previous TKIs under the current compassionate use program. Methods: We retrospectively collected data from 31 patients treated with asciminib in 25 centers under compassionate use program. Data collecting was performed between October 2018 and June 2020. Patients baseline characteristics are shown in table 1. Most patients were heavily pretreated with 28 patients receiving 3 or more TKIs previous to asciminib. Eleven patients (35.5%) had been treated with ponatinib at some point throughout the disease. Twelve patients showed BCR-ABL1 mutations (only 1 case with T315I mutation). Switch to asciminib was due to intolerance in 22 patients and due to resistance in the remaining 9. Median dose of asciminib was 80mg per day (40mg every 12 hours). Treatment responses were evaluated according to European Leukemia Net recommendations. Data compilation and analysis were performed with REDCap Software and IBM SPSS (Version 25.0). Results: Median time on asciminib for the entire cohort was 35 weeks. Regarding toxicities, 13 patients (42%) experienced mild extra-hematological side effects (grade 1-2) being the most frequent fatigue (19%), joint pain (16%) and nausea (9%). Four patients (12,9%) showed severe (grade 3-4) extra-hematological events: fatigue, hepatotoxicity, hypertension and pericardial effusion (1 patient each). Three patients (9,7%) suffered from grade 4 thrombocytopenia, 2 of them associating grade 4 neutropenia. All toxicities according to previous TKIs adverse effects as well as cross-intolerance data is shown in table 2. Dose reduction had to be carried out in 9 patients (29%), 7 of those with temporary treatment interruptions; most owing to hematological adverse effects. In terms of efficacy (Graph 1), probability of reaching or at least maintaining previous response was 100%, 61.3% and 35.5% for complete hematological response (CHR), complete cytogenetic response (CCyR) and major molecular response (MMR), respectively. Regarding probabilities to improve previous responses, rates of CCyR and MMR were, respectively, 22,2% (2/9) and 22,2% (2/9) for resistant patients and 44% (4/9) and 62,5%. (10/16) for intolerant group. Amid the 11 patients previously treated with ponatinib, 3 patients (27,3%) showed improvement of response achieving at least MMR, 2 of them from the TKI-intolerant group and 1 from the TKI-resistant group. The median follow-up time was 40 weeks, after which 27 patients (87.1%) continued with asciminib. Treatment cessation happened in 2 patients due to progression to blastic phase and in 2 patients due to lack of efficacy. No patients discontinued due to side effects. Conclusion: The data presented, similar to that known from clinical trials, supports the use of asciminib in routine clinical practice in CML patients failing to previous TKIs. Disclosures Garcia-Gutiérrez: Novartis: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Bristol-Myers Squibb: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Pfizer: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Incyte: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding.

Background: Background: Acute Myeloid Leukemias arising after cytotoxic therapy (t-AML) or with myelodysplasia-related changes (AML-MRC) share adverse risk features and poor outcomes after standard 3+7 chemotherapy. In a randomized clinical trial, CPX-351 has shown superior overall survival (OS) compared to standard anthracyclinecytarabine schedule in these AML subtypes. Aims:Aims: to evaluate the effectiveness of CPX-351 treatment in a real-world setting. Methods:Methods: adult t-AML and AML-MRC patients who have been treated upfront with CPX-351 in 35 Spanish centers between 2018 and 2021. All patients were included in the PETHEMA registry (NCT02606825). Primary end-point was OS. Secondary end points were complete remission with or without hematological recovery (CR/CRi), proportion of minimal residual negativity (MRD), rate of allogeneic hematopoietic stem cell transplant (HSCT) and safety. Results: Results:CPX-351 was administered to 74 patients as first induction chemotherapy. Median age was 67 (63-71) years, with 40% (30/74) of female patients. ECOG performance status score was 0-1 in 85% (53/62) patients. A diagnosis of t-

Background Idelalisib is a PI3-kinase inhibitor specific for the delta isoform, approved (in combination with rituximab or ofatumumab) for the treatment of adult patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (R/R CLL). Although the efficacy of idelalisib was reported in clinical trials, it is unclear how this translates into Real World. Methods A non-interventional retrospective study was conducted in Spain to describe the clinical characteristics and outcomes of patients diagnosed with R/R CLL that started treatment with idelalisib between 1 February 2015 and 31 December 2017. The Time from start of idelalisib treatment to either the start of a new anti CLL therapy or death (Time to Next Treatment or Death - TNTD) was defined as primary endpoint. Secondary endpoints included overall survival (OS), time to discontinuation (TTD) and safety, especially Adverse Events of Special Interest (AESI): ≥ grade 3 transaminase elevations, diarrhea /colitis, pneumonitis, neutropenia,Cytomegalovirus, bacterial, fungal and respiratory virus infections (RVI),Pneumocystis jirovecii pneumonia (PjP). Results Investigators from 21 centers included 77 patients in the study. The median age was 72.1 years (48-86) and 67.5% (n=52) were male. The main baseline characteristics were: Binet stage B-C in 32.5% (n=25), 17p deletion or TP53 mutation in 35.1% (n=27) and the median number previous lines of therapy was 4 (1-16). With a median follow up time of 14.4 months (1.2-44.4), 27 patients (35.1%) had started a new treatment and 19 (24.7%) had died. The median TNTD was 17.1 months (95% CI 14.0-22.3) in the overall population and 13.8 months (95% CI 7.9-15.2) in patients that discontinued idelalisib. The median OS has not been reached, with a cumulative probability of surviving at 1 and 2 years of 0.84 (95% CI 0.73-0.91) and 0.67 (95% CI 0.52-0.78). During follow-up 54 patients (70.1%) discontinued idelalisib: 39 (72.3%) due to toxicity and 10 (18.5%) due to disease progression. The median TTD was 13.0 months (95% CI 7.7-15.8); 5.3 months (95%CI 3.8-8.0) in patients who discontinued treatment due to serious adverse events (SAE) or AESI and 10.5 months (95% CI 0.5-16.0) in those who did so due to progressive disease. A total of 355 AEs were reported, of which 29.0% (n=103) were SAE. 181 AESIs were recorded: the most frequent were neutropenia (n=67; 22 grade >3), diarrhea/colitis (n=37; 14 grade >3) and bacterial infections (n=24; 14 grade >3). Other AESI were CMV infections (n=11), grade ≥ 3 pneumonitis (n=7), RVI (n=6), fungal infections (n=5), grade ≥ 3 transaminase elevations (n=3) and PjP (n=1). The median time from Idelalisib start to first AESI was 9.5 months (95%CI 5.5-15.3). During follow-up, 19 deaths were registered, 10 of which were caused by idelalisib-related SAEs (4 respiratory infections, 2 pneumonitis, 1 diarrhea/colitis). The time from SAE related to idelalisib that led to death, to death was 0.8 months (95% CI 0.7-1.7). Conclusions This real world study shows results of effectiveness of idelalisib consistent with the efficacy findings of the 312-0116 clinical trial. Toxicity was the most common reason for idelalisib discontinuation. Findings of adverse events were consistent with the known safety profile of idelalisib and no new drug-related adverse events were identified. This is a Gilead Sciences sponsored study. Disclosures Perez Encinas: GILEAD SCIENCES: Research Funding; CELGENE: Consultancy; JANSSEN: Consultancy. Lopez Jimenez:GILEAD SCIENCES: Honoraria, Other: Education funding. Ortiz:GILEAD SCIENCES: Research Funding. Cordoba:Pfizer: Consultancy; Celgene: Consultancy, Honoraria, Speakers Bureau; FUNDACION JIMENEZ DIAZ UNIVERSITY HOSPITAL: Employment; Roche: Honoraria, Speakers Bureau; Kyowa-Kirin: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Research Funding, Speakers Bureau; Servier: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. Ramirez Payer:GILEAD SCIENCES: Research Funding. González-Barca:Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celtrion: Consultancy; AbbVie: Consultancy, Honoraria; Kiowa: Consultancy; Takeda: Honoraria; Celgene: Consultancy. Martín Sánchez:GILEAD SCIENCES: Research Funding. Sanchez:Gilead Sciences: Research Funding. Baltasar Tello:JANSSEN: Consultancy, Honoraria; ABBVIE: Honoraria; ROCHE: Honoraria; GILEAD: Honoraria. Amutio:NOVARTIS: Consultancy; JANSSEN: Consultancy, Honoraria; CELGENE: Consultancy, Honoraria; ROCHE: Honoraria; GILEAD SCIENCES: Consultancy, Honoraria; TAKEDA: Consultancy; GSK: Honoraria; BMS: Honoraria; JAZZ PHARMACEUTICALS: Honoraria; MUNDIPHARMA: Consultancy. Vidal Maceñido:GILEAD SCIENCES: Research Funding. Fernandez:GILEAD SCIENCES: Research Funding. Loscertales:Gilead: Honoraria; AbbVie: Honoraria; AstraZeneca: Honoraria; Janssen: Honoraria; Roche: Honoraria. Rodríguez:GILEAD SCIENCES: Research Funding. Alaez:ROCHE: Consultancy. Ramroth:Gilead Sciences: Employment. Palla:Gilead Sciences: Employment.