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

Clinical Lymphoma, Myeloma & Leukemia September 2021 S339 Abstracts and found that more than fifty percent of mutation frequencies were distributed between TET2 (15%), ASXL1 (15%), SRSF2 (11%), CBL (6%), and RUNX1 (5%). There was a significant association between ASXL1 mutation and worse overall survival (HR=2.34, p=0.028). We also found a tentative suggestion of improved survival with TET2 (HR=0.56, p=0.13). Both RAS pathway mutations and spliceosome component mutations, although present in a significant portion of the patient cohort (4 7 % and 16%, respectively), showed no apparent association with survival (HR=1.34, p=0.43, and HR=1.36, p=0.41). Older patients (> 7 5 years) displayed a slightly better survival probability than their younger counterparts (HR=1.63, p=0.19). Co n clusio n s: In our hypothesis-generating report, we confirm the association of ASXL1 mutation and worse prognosis and describe possible favorable overall survival from patients with the presence of a TET2 mutation. Further work is planned to confirm these findings in larger cohorts and their impact on response to hypomethylating agents. Ack n owledg m e n t: Research reported in this publication utilized the Research Informatics Shared Resource at Huntsman Cancer Institute at the University of Utah and was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA042014. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Keywords: MDS, chronic myelomonocytic leukemia, myelodysplastic/ myeloproliferative neoplasm MDS-090 Phase II Study of the IDH2 Inhibitor Enasidenib in Patients with High- Risk IDH2-Mutated Myelodysplastic Syndromes (MDS) Sangeetha Venugopal 1 *, Courtney D. DiNardo 1 , Koichi Takahashi 1 , Marina Konopleva 1 , Sanam Loghavi 3 , Gautam Borthakur 1 , Amy DeZern 2 , Lucia Masarova 1 , Naval Daver 1 , Nicholas J. Short 1 , Yesid Alvarado 1 , Farhad Ravandi 1 , Guillermo Montalban-Bravo 1 , Koji Sasaki 1 , Ricardo Delumpa 1 , Mikkael A. Sekeres 4 , Bhumika Patel 5 , Gail J. Roboz 6 , Hagop M. Kantarjian 1 , Guillermo Garcia-Manero 1 1 Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA, 2 Division of Hematologic Malignancies, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA, 3 Department of Hematopathology, Division of Pathology and Laboratory Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA, 4 Division of Hematology, Sylvester Comprehensive Cancer Center, University of Miami, FL, USA, 5 Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA, 6 Division of Hematology & Oncology, Weill Cornell Medical Center, New York, NY, USA Co n text: Isocitrate dehydrogenase 2 (IDH2) mutations occur in 5% of patients (pts) with MDS. Enasidenib (ENA) is a selective oral mutant-IDH2 inhibitor with single-agent activity in relapsed/ refractory AML. Objecti v e: To evaluate the efficacy and tolerability of ENA, as monotherapy or in combination with azacitidine (AZA), in pts with higher-risk IDH2-mutated MDS (NCT033835 7 5). D esig n a n d Setti n g: Multi-institutional, open-label, two-arm, non- randomized, phase II study. Patie n ts a n d I n ter v e n tio n s: Pts with higher-risk (R-IPSS > 3, or high-molecular-risk MDS/CMML, or RAEB-T MDS) enrolled in Arm A and received ENA100 mg orally daily for 14 or 28 d of each 28-d cycle + AZA 7 5 mg/m 2 IV or SC on d 1– 7 of each cycle (ENA+AZA). ENA duration was decreased to 14 d of each cycle, per amendment, to mitigate cytopenias. Pts with refractory or progressive MDS prior to HMA therapy enrolled in Arm B and received ENA alone (ENA), continuously, in 28-d cycles. Mai n Outco m e Measures: The primary endpoint was overall response rate (ORR) [complete remission (CR), marrow CR (mCR), partial remission (PR), and hematologic improvement (HI)]. Other endpoints include safety and survival outcomes. Results: 48 pts received ENA+AZA (n = 26) or ENA (n = 22). The median age was 7 3 yrs (range, 46–83). Most pts ( 7 2%) had HMR: ASXL1 (39%) and RUNX1 (1 7 %). Common Tx-related grade 3–4 AEs in the ENA+AZA arm were neutropenia (64%), thrombocytopenia (28%), and anemia (8%); these occurred in 10%, 0%, and 5%, in the ENA arm, respectively. IDH differentiation syndrome occurred in 3 pts (12%) in the ENA+AZA and 5 pts (24%) in the ENA arm. In response-evaluable pts (n = 46), ORR was 84% (n = 21/25; 24% CR + 8% PR+44% mCR+ 8% HI] in the treatment-naïve Arm A and 43% (n = 9/21; 24% CR+5%PR+5% mCR+10% HI) in the HMA failure ENA arm B. After a median follow-up of 12.6 mo, median OS was 32.2 mo in the ENA+AZA arm and 21.3 mo in the ENA arm. Co n clusio n s: ENA is well-tolerated and shows promising efficacy in IDH2-mutated higher-risk MDS. Follow-up and accrual are ongoing. Keywords: MDS, IDH2, enasidenib, AG-221 MDS-124 Patients with Improved Clinical Disease Parameters Also Display Improved Fatigue Following Pegcetacoplan Treatment in Paroxysmal Nocturnal Hemoglobinuria: Post Hoc Analyses from the PEGASUS Trial at Week 48 David Cella 1 *, Sujata Sarda 2 , Ray Hsieh 3 , Jesse Fishman 2 , Zalmai Hakimi 4 , Katelyn Cutts 3 , William Lenderking 3 1 Northwestern University, Chicago, IL, USA, 2 Apellis Pharmaceuticals, Inc., Waltham, MA, USA, 3 Evidera, Waltham, MA, USA, 4 Swedish Orphan Biovitrum (Sobi), Stockholm, Sweden Co n text: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease involving complement-mediated hemolysis. Pegcetacoplan (PEG; a C3-inhibitor recently approved by the FDA) improved fatigue and was superior to eculizumab (ECU; C5-inhibitor) in improving hemoglobin levels at Week 16 (phase 3 PEGASUS; NCT03500549). Objecti v e: These post hoc analyses