Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S364 had MDS-RS subtype; SF3B1 was detected in 85.7% and 43% were red blood cell high transfusion burden transfusion dependent. The majority had prior ESA treatment 89% (25). Additionally, 12 pts (43%) had prior hypomethylating agent (HMA) treatment and 11 pts (39%) had prior lenalidomide (Len). Luspatercept 1.33 mg/kg dose escalation was given to 23 pts; 25 pts received 1.75 mg. The overall HI rate to luspatercept combined with ESA was 36% (10/28). HI according to baseline RBC-TB were observed in 33% (1/3) NTD, 56% (6/13) LTB and 33% HTB (4/12) pts respectively. Five out 7 pts who responded originally to luspatercept alone (2º failure) responded to ESA add on whereas only 3 out of 18 pts who did not respond to luspatercept monotherapy (1º failure) responded when ESA was added. With upfront ESA + luspatercept combination, 2 of 3 pts responded. No responses to combination ESA/luspatercept were observed among SF3B1 wild type pts (n=4). Baseline serum erythropoietin (epo) levels (median 119.5 U/L) were available for 18 pts at time of referral, 25% of pts (2/8) with serum epo 200-500 u/L responded and 40% of pts (4/10) with serum epo less than 200 U/L responded. There was a trend of higher response among HMA- and Len-naïve pts. The hematologic improvement (HI) rate was 25% after HMA failure compared to 44% in HMA naïve pts (P=0.3). The HI rate was 18% for Len failure compared to 47% Len-naïve pts, (P=0.1). Conclusion: This is the first proof-of-principle data confirming synergistic activity combining luspatercept and ESA. Predictors of response included prior response to luspatercept monotherapy/frontline combination compared to primary luspatercept failure, serum epo levels <500, SF3B1 mutation, and being HMA/Len treatment-naïve. Keywords: MDS, luspatercept, ESA MDS-367 A Phase II/III Trial of Oral Azacitidine (Oral‑AZA) in Patients With Low‑ or Intermediate‑Risk Myelodysplastic Syndromes (MDS) Guillermo Garcia-Manero MD1, Valeria Santini MD, PhD2, Pierre Fenaux MD, PhD3,4, Takahiro Suzuki MD5, Mikkael A. Sekeres MD6, Jun He PhD7, Ronit Barkalifa PhD7, Carlos E. Vigil MD7, Thomas Prebet MD, PhD7, Rami Komrokji MD8, Aristoteles Giagounidis MD9 1MD Anderson Cancer Center, Houston, TX, USA. 2MDS Unit, AOU Careggi, University of Florence, Florence, Italy. 3Service d’Hématologie Séniors, Assistance Publique-Hôpitaux de Paris and Université Paris, Paris, France. 4Hôpital Saint-Louis, Paris, France. 5Kitasato University School of Medicine, Sagamihara-shi, Kanagawa, Japan. 6Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA. 7Bristol Myers Squibb, Summit, NJ, USA. 8H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. 9Marien Hospital Düsseldorf, Düsseldorf, Germany Context: In early trials, 14- and 21-day (d) dosing regimens of oral-AZA were well tolerated and induced hematologic improvement (HI) in patients with lower-risk (LR) MDS. In a Phase III trial, Oral-AZA 300 mg QD for 21d per 28d cycle significantly improved the rate of red blood cell (RBC) transfusion independence (TI) and induced durable HI versus placebo in patients with LR-MDS, although grade 3/4 cytopenias were common in the Oral-AZA arm. These findings support further evaluation of Oral-AZA in MDS. Objective: Evaluate safety and efficacy of the 14d Oral-AZA regimen in patients with low- or intermediate-risk MDS. Design: An ongoing, multicenter, randomized, Phase II/III trial (CA055-026; NCT05469737). Patients: Adults with International Prognostic Scoring System Revised (IPSS-R)-defined low- or intermediate-risk MDS, Eastern Cooperative Oncology Group performance status ≤2, and ≥1 cytopenia (anemia, thrombocytopenia, or neutropenia), excluding patients with an absolute neutrophil count <0.5 × 109/L ≤1 week of randomization. Interventions: Phase II will enroll and randomize ~42 patients 1:1 to receive Oral-AZA 200 or 300 mg QD for 14d per 28d cycle, plus best supportive care (BSC), to determine the recommended Phase III dose. Phase III will enroll and randomize ~188 additional patients 1:1 to Oral-AZA at recommended Phase III dose or placebo for 14d per 28d cycle, plus BSC. Patients in the placebo arm with stable disease at Cycle 6 or disease progression after ≥3 cycles may opt to cross over into the Oral-AZA arm. Patients benefitting from Oral-AZA may continue treatment in an extension phase. Main Outcome Measures: Phase II primary endpoints are safety and complete remission (CR) rate in ≤6 treatment cycles. Secondary endpoints are overall response rate (ORR), packed RBC-TI and platelet-TI sustained for 84d in ≤6 cycles. ORR includes CR, partial remission, marrow CR, and HI. Phase III primary endpoint is CR in ≤6 treatment cycles and key secondary endpoint is 84d packed RBC-TI. Other secondary endpoints include those in Phase II, plus overall survival, event-free survival, time to AML progression, iron parameters, health-related quality of life, healthcare resource utilization, and safety parameters. Conclusion: Recruitment began December 2022 and is ongoing. Previously Published: EHA2023 Congress. Keywords: MDS, myelodysplastic syndrome, oral azacitidine, clinical trial, myeloid malignancies MDS-392 Outcomes With Allogeneic Hematopoietic Stem Cell Transplant in Therapy‑Related Myelodysplastic Neoplasms: A Systematic Review and Meta‑Analysis Moazzam Shahzad MD1,2, Muhammad Fareed Khalid MD3, Atif Butt MD4, Muhammad Kashif Amin MD5, Muhammad Shan Ul Abedin MD6, Maheen Zaidi MD7, Sudeepthi Bandikatla MD1,2, Mohammad Ammad-UdDin MD1,2, Michael Jaglal MD1 1H.Lee Moffitt Cancer Center, Tampa, USA. 2University of South Florida, Tampa, USA. 3Danbury Hospital, Danbury, USA. 4St. Mary’s Medical Center, Huntington, USA. 5Kansas University Medical Center, Kansas City, USA. 6Abingdon Medical Center, Abingdon, USA. 7Baptist Memorial Hospital-North Mississippi, Oxford, USA Background: The prognosis of therapy-related myelodysplastic syndrome (t-MDS) is dismal with current treatment options. Allogeneic hematopoietic stem cell transplant (allo-HCT) is the
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