Clinical Lymphoma, Myeloma & Leukemia, Vol.21, Suppl.1 - September 2021

Clinical Lymphoma, Myeloma & Leukemia September 2021 S341 Abstracts MDS-128 Azacitidine and Venetoclax Combination for Upfront Treatment of Higher-Risk Myelodysplastic Syndromes Najla Al Ali, David Sallman, Onyee Chan, Eric Padron, Kendra Sweet, Andrew Kuykendall, Jeffrey Lancet, Rami Komrokji* Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL, USA Co n text: Azacitidine (aza) remains the backbone of treating higher-risk MDS patients (pts), with less than 20% of pts achieving complete response (CR) and median overall survival of 14–18 months. Ongoing studies in higher-risk MDS are assessing the role of adding venetoclax (ven) to aza in higher-risk MDS. Objecti v e: We report, here, single-institution experience of aza/ven combination in the upfront treatment of higher-risk MDS, comparing it to historical aza alone. D esig n : We identified 35 pts who received aza/ven for intermediate or higher-risk MDS by R-IPSS compared to 11 7 5 similar-risk MDS pts who historically received aza upfront therapy alone. Results: The median follow-up for the aza/ven group was 15 months (mo) compared to 93 mo for aza alone. No differences were observed in baseline demographic or disease characteristics comparing aza/ven group to aza alone except for higher rates of ASXL-1 and N-RAS somatic mutations (SM) among aza/ven treated pts. There was no difference in median OS among the two groups: median OS was 20 mo for both groups. The CR/marrow CR (mCR) rate was higher with the aza/ven combination, 7 1% (31%/40%), compared to 25% for aza alone (13%/12%) (p<.005). Among pts with ASXL- 1 SM, the CR rate was 4 7 % compared to 9% for aza alone (p <.005). More pts treated with aza/ven proceeded to allogeneic hematopoietic stem cell transplant (AHSCT) (40% vs 23%, p=.04). The median OS for pts treated with aza/ven followed by AHSCT was not reached compared to 31 mo for aza alone followed by AHSCT (p=.1 7 ). The 2-year survival rate for pts who underwent AHSCT was 90% for aza/ven compared to 51% for the aza alone group. Co n clusio n : Aza/ven combination is associated with higher responses overall and among ASXL-1 SM higher-risk MDS pts and encouraging early data support aza/ven as a bridge to AHSCT, with 90% 2-year OS. Keywords: MDS, azacitidine, venetoclax MDS-134 Efficacy and Safety at 48 Weeks of Pegcetacoplan in Adult Paroxysmal Nocturnal Hemoglobinuria Patients with Suboptimal Response to Prior Eculizumab Treatment Ilene C. Weitz 1 *, Régis Peffault de Latour 2 , Jeffrey Szer 3 , Alexander Röth 4 , Britta Höchsmann 5 , Jens Panse 6 , Kensuke Usuki 7 , Morag Griffin 8 , Jean-Jacques Kiladjian 9 , Carlos M. de Castro 10 , Hisakazu Nishimori 11 , Lisa Tan 12 , Mohammed Al-Adhami 13 , Pascal Deschatelets 13 , Cedric Francois 13 , Federico Grossi 13 , Antonio Risitano 14,15 , Peter Hillmen 8 1 Jane Anne Nohl Division of Hematology, Keck-USC School of Medicine, Los Angeles, CA, USA, 2 French Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria, Assistance Publique – Hôpitaux de Paris, Université de Paris, Paris, France, 3 Department of Clinical Haematology, Peter MacCallum Cancer Centre & Royal Melbourne Hospital, Melbourne, VIC, Australia, 4 Department of Hematology and Stem Cell Transplantation, University Hospital Essen, University of Duisburg-Essen, Essen, Germany, 5 University of Ulm and Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service and University Hospital Ulm, Institute of Transfusion Medicine, Ulm, Germany, 6 Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany, 7 Department of Hematology, NTT Medical Center Tokyo, Tokyo, Japan, 8 Department of Haematology, St James University Hospital, Leeds, United Kingdom, 9 Centre d’Investigations Cliniques, Hôpital Saint-Louis; Assistance Publique – Hôpitaux de Paris; Université de Paris, Paris, France, 10 Duke University School of Medicine, Durham, NC, USA, 11 Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan, 12 Lisa Tan Pharma Consulting Ltd, Cambridge, United Kingdom, 13 Apellis Pharmaceuticals, Inc., Waltham, MA, USA, 14 Hematology and BMT Unit, AORN San Giuseppe Moscati, Avellino, Italy, 15 Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy Co n text: Pegcetacoplan (PEG) is a C3 complement inhibitor recently approved by the FDA for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). PEG was superior to eculizumab (ECU; C5-inhibitor) in improving hemoglobin levels at week 16 during the phase 3 PEGASUS trial (NCT03500549) in patients with suboptimal response to prior ECU treatment. Objecti v e: We report on efficacy and safety of PEG and results from a post hoc time- aligned analysis based on start of PEG dosing. D esig n : Eighty PNH patients (  18 years, hemoglobin levels <10.5 g/dL despite stable ECU treatment [  3 months]) were enrolled. Following a 4-week run-in, patients were randomized (1:1) to PEG or ECU monotherapy for the randomized controlled period (RCP) through week 16, before initiating an open-label period (OLP) through week 48, where ECU patients completed a second run-in before switching to PEG monotherapy (ECU-to-PEG), and PEG patients continued PEG monotherapy (PEG-to-PEG). Key endpoints included change from baseline (CFB) in hemoglobin levels and incidence of adverse events (AEs). Timepoints were manually aligned based on start of PEG dosing (PEG-to-PEG: day 1; ECU-to-PEG: week 20) to compare changes in hemoglobin levels between groups. Results: PEG-to- PEG patients achieved sustained improvements in hemoglobin levels at week 16 through the OLP (week 48 mean hemoglobin level: 11.3 g/dL; CFB: 2.5 g/dL). ECU-to-PEG patients displayed improved hemoglobin levels during the OLP (week 48 mean hemoglobin level: 11.6 g/dL; CFB: 2.9 g/dL). Timepoint alignment demonstrated no significant difference (p=0.64) between improvements in hemoglobin levels at 28 and 48 weeks among PEG-to-PEG and ECU-to-PEG