Clinical Lymphoma, Myeloma & Leukemia, Vol.22, Suppl.2 - October 2022

Abstracts Clinical Lymphoma, Myeloma & Leukemia October 2022 S310 MDS-353 Clinical Outcome of Myelodysplastic Syndrome Progressing on Hypomethylating Agents With Evolving Frontline Therapies: Continued Challenges and Unmet Needs Ahmad Ghorab MD, MSc 1 , Aref Al-Kali MD 2 , Michelle Elliot MD 2 , Naseema Gangat MBBS 2 , Hasan Alkhateeb MD 2 , Mithun Shah MD, PhD. 2 , Cecilia Arana Yi MD 3 , Hemant Murthy MD 1 , Mohamed Kharfan Dabaja MD, MBA 1 , Ayalew Tefferi MD 2 , Mrinal Patnaik MBBS 2 , Mark Litzow MD 2 , Talha Badar MBBS, MD 1 1 Mayo Clinic, Jacksonville, USA. 2 Mayo Clinic, Rochester, USA. 3 Mayo Clinic, Phoenix, USA I n troductio n : Historically, the clinical outcome of myelodysplastic syndrome (MDS) patients progressing on hypomethylating agent (HMA) therapy is dismal. We sought to explore the outcome of MDS patients progressing after HMA therapy in the era of novel therapies. Methods: We retrospectively analyzed treatment outcomes of 7 1 MDS patients who progressed on HMA and were treated at Mayo Clinic between 2015 and 2021. Results: The median age of patients was 6 7 years (range, 36–91 years). Therapy-related MDS was diagnosed in 24% (n=1 7 ) of patients, whereas 48% of patients (n=34) had complex cytogenetics (CG). Large proportions of patients had IPSS-R high-risk (2 7 %) and very-high-risk disease (46%) at baseline. The most commonly occurring mutations (  10% of cases) were TP53 (44%), ASXL1 (21%), RUNX1 (14%), RAS (13%), and TET2 (11%). Among patients with MDS-EB1/EB2 (n= 23), 7 (30%) patients achieved complete remission (CR) and 2 (9%) had marrow CR. Among the 42 AML patients who progressed after HMA therapy and received induction chemotherapy, 36% achieved CR (n=8) or CR with incomplete count recovery (CRi, n= 7 ). Five (10%t of 48 patients who progressed to AML did not receive induction chemotherapy due to poor performance status. Overall, 14 (20%) patients progressing on HMA successfully bridge to alloHCT. The proportions of patients who achieved CR based on therapy at HMA progression were 46% (n=19), 14% (n=2), 6 7 % (n=2), and 12.5% (n=1) with Venetoclax-based combination, CPX-351, intensive chemotherapy, and other low-intensity therapies, respectively (p=0.053). Complex CG (p=0.04) and TP53 mutation (p=0.04) predicted significantly inferior CR rates. After excluding 5 patients who did not receive further therapy after HMA progression, the median OS was 9.3 months (95% CI: 4.65–14.0 months). On multivariate analysis (MVA), achievement of CR/CRi retained significance for improved OS (p=0.01), whereas TP53 mutation (p=0.001) and AML diagnosis at HMA progression (p=0.01) retained significance for inferior OS (p=0.004). Despite demonstrating favorable significance for OS in the univariate analysis, alloHCT did not retain significance for better OS in the MVA (p=0.38). Co n clusio n s: Our report suggests modest improvement in survival of MDS patients progressing on HMA compared to historical data. Effective therapies are needed to improve outcomes for these patients. Keywords: MDS, progressing on hypomethylating agents, clinical outcome MDS-406 Prognostic Implication of the Molecular Profiles of Patients With Hypocellular Myelodysplastic Syndrome Kunhwa Kim MD, MPH, Faustine Ong MD, Guilermo Montalban-Bravo MD, Rashmi Kanagal Shamanna MD, Tapan Kadia MD, Elias Jabbour MD, Yesid Alvarado MD, Koji Sasaki MD, Xia Qing Dong MS, Sherry Pierce BSN, Carlos Bueso- Ramos MD, Hagop Kantarjian MD, Chien Kelly MD, Guillermo Garcia-Manero MD The University of Texas MD Anderson Cancer Center, Houston, USA Co n text: Hypocellular myelodysplastic syndrome (hMDS) is a subset of MDS that has not been fully characterized. This study aimed to better identify the clinical characteristics and molecular profile of hMDS and study the prognostic impact of mutations in hMDS. D esig n : We conducted a retrospective review of patients with newly diagnosed MDS in a single tertiary cancer center registry from 2010 to 2021. Results: Of 1,899 patients with MDS, 1 7 6 (10%) patients had hMDS. The median follow-up period was 19.5 months. hMDS patients were more likely to be younger and have therapy-related disease and more thrombocytopenic and neutropenic than normo/ hypercellular MDS (non-hMDS). All other clinical characteristics were comparable. The distributions of IPSS-R cytogenetic scores (  3, or <3) were comparable. hMDS patients had similar overall survival (OS) to non-hMDS (median 28.3 vs. 29.0 months) or AML transformation rates (23% vs. 19%). These findings were maintained after multivariate adjustment. Hypocellularity did not affect survival in either de novo or t-MDS. We further analyzed 1,352 ( 7 1%) pts with mutation data available. Patients with hMDS had less frequent ASXL1, RUNX1, TET2, or IDH1 mutations, whereas the frequency of TP53 and RAS pathway mutations were comparable. In de novo MDS, hMDS patients had less frequent RUNX1, SRSF2, or TET2 mutations. In t-MDS, hMDS pts had less frequent TP53 or U2AF1 mutations. The survival of hMDS can be stratified by IPSS-R with some overlaps. In hMDS, mutations in the RAS pathway or TP53 were associated with inferior OS, whereas TET2 mutations correlated with superior OS. Based on the mutation data, patients were stratified into 3 groups: (1) with TET2 mutations, (2) with TP53 or RAS pathway mutations without TET2 mutations, and (3) without TET2/TP53/RAS mutations. The TET2 mutant group showed marginally better mOS (HR 0.50, P =0.081), and the TP53/RAS pathway group showed inferior mOS (HR 2. 7 4, P =.005) compared with the group without TET2/TP53/RAS pathway mutation. Co n clusio n s: Patients with hMDS had similar outcomes to patients with non-hMDS but exhibit distinct molecular profiles; hMDS had less frequent driver mutations commonly seen in non-hMDS. The integration of molecular profiles into risk stratification in hMDS could be a study of interest. Keywords: MDS, myelodysplastic syndrome, hypocellular, mutations