Amer Zeidan, MBBS, and Guillermo Garcia-Manero, MD, discuss current treatment trends in myelodysplastic syndromes.

Dissecting the Current Treatment Landscape in MDS

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Dr Zeidan on Classification and Treatment Updates in MDS

Amer Zeidan, MBBS, associate professor, internal medicine (hematology), director, Early Therapeutics Research, Hematology, leader, Clinical Research Team for Leukemias and Myeloid Malignancies, chair, Protocol Review Committee I, assistant medical director, Clinical Trials Office, director, Hematology Research Seminar Series, Hematology, member, Executive Committee, member, Clinical Trials Advisory Committee, interim chief, Hematologic Malignancies, Yale Cancer Center, discusses classification and treatment updates for patients with myelodysplastic syndrome (MDS).

Primary updates concerning the classification of MDS in 2022 and 2023 included the implementation of the 2022 World Health Organization Classification system and the International Consensus Classification system, both of which use genetically informed approaches to categorize patients with MDS, Zeidan says. However, the existence of 2 classification systems can complicate patient categorization and subsequent treatment decision-making in the oncology community. This has prompted several initiatives, including those conducted at Yale Cancer Center, to align these systems, Zeidan notes. Another development in MDS classification is the incorporation of the Molecular International Prognostic Scoring System, which integrates molecular alterations into the risk-stratification process for patients with MDS, Zeidan explains.

Regarding therapeutic advances in lower-risk MDS, 

 (Reblozyl) to include erythropoiesis stimulating agent (ESA)–naive patients with lower-risk MDS with anemia who may require regular red blood cell (RBC) transfusions, regardless of ring sideroblast status. This protein-transforming growth factor pathway ligan trap was 

 for patients with very low– to intermediate-risk MDS with ring sideroblasts who were anemic and transfusion dependent after progression on ESAs. That regulatory decision was supported by findings from the phase 3 MEDALIST trial (NCT02631070).

The phase 3 COMMANDS trial (NCT03682536) provided further therapeutic insights on the use of frontline luspatercept in transfusion-dependent patients with lower-risk MDS, Zeidan emphasizes. In COMMANDS, patients were randomly assigned to receive luspatercept or short-acting ESAs. This trial demonstrated that 58.5% of patients who received luspatercept achieved RBC transfusion independence for at least 12 weeks vs 31.2% of those who received ESAs.

Amer Zeidan, MBBS, discusses classification and treatment updates for patients with myelodysplastic syndrome. 

Amer Zeidan, MBBS, associate professor, internal medicine (hematology), director, Early Therapeutics Research, leader, Disease Aligned Research Team for Leukemias and Myeloid Malignancies, chair, Protocol Review Committee I, assistant medical director, Clinical Trials Office, director, Hematology Research Seminar Series, member Executive Committee, Yale Cancer Center, discusses topline efficacy findings from the phase 3 IMerge trial (NCT02598661) of imetelstat in patients with transfusion-dependent lower-risk myelodysplastic syndrome (LR-MDS).

IMerge evaluated the efficacy and safety of imetelstat compared with placebo in patients with heavily transfusion-dependent LR-MDS without 5q deletions who had relapsed on or were refractory to erythropoiesis-stimulating agents. In both arms, patients had a median of 6 prior red blood cell (RBC) transfusions per 8 weeks at baseline. The primary end point of this trial was RBC transfusion independence at 8 weeks.

The transfusion-independence rates at 8 weeks, 16 weeks, 24 weeks, and 1 year were 39.8%, 31.4%, 28.0%, and 13.6%, respectively, in the imetelstat arm vs 15.0%, 6.7%, 3.3%, and 1.7%, respectively, in the placebo arm. In the patients who received between 4 and 6 prior RBC transfusions, the 8-week transfusion-independence rates were 45.2% and 21.1% in the imetelstat and placebo arms, respectively. In the patients who received more than 6 prior RBC transfusions, the 8-week transfusion-independence rates were 33.9% and 7.4% in the imetelstat and placebo arms, respectively. In total, 83% of patients who received imetelstat and achieved 8-week RBC transfusion independence had a single continuous period of transfusion independence. In addition, the median duration of transfusion independence was 51.6 weeks in the imetelstat arm vs 13.3 weeks in the placebo arm.

These rates of transfusion independence with imetelstat were observed in patients regardless of genetic mutation status, Zeidan says. Patients with 

 mutations achieved greater variant allele frequency reductions with imetelstat vs placebo.

Future research with the IMerge trial will focus on findings including patient-reported outcomes and changes in patient fatigue, Zeidan notes. Imetelstat is an effective agent for patients with LR-MDS with gene mutations and heavy baseline transfusion needs, Zeidan concludes.

Dr Zeidan reports honoraria from AbbVie, Acceleron Pharma, Agios, Astellas Pharma, BeyondSpring Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Bristol-Myers Squibb/Celgene, Daiichi Sankyo, Epizyme, Geron, Ionis Pharmaceuticals, Jazz Pharmaceuticals, Novartis, Otsuka, Pfizer, Seagen, Taiho Pharmaceutical, Takeda, and Trovagene; consulting or advisory roles with AbbVie, Acceleron Pharma, Agios, Astellas Pharma, BeyondSpring Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Epizyme, Geron, Incyte, Ionis Pharmaceuticals, Jazz Pharmaceuticals, Novartis, Otsuka, Pfizer, Seagen, Taiho Pharmaceutical, and Takeda; research funding from AbbVie (Inst), ADC Therapeutics (Inst), Aprea AB (Inst), Astex Pharmaceuticals (Inst), AstraZeneca/MedImmune (Inst), Boehringer Ingelheim (Inst), Bristol-Myers Squibb (Inst), Celgene (Inst), Incyte (Inst), Novartis (Inst), Pfizer (Inst), Takeda (Inst), and Trovagene (Inst); and travel, accommodations, and expenses from Celgene, Novartis, Pfizer, and Trovagene.

Amer Zeidan, MBBS, discusses topline efficacy findings from the IMerge trial of imetelstat in patients with transfusion-dependent lower-risk myelodysplastic syndrome.

Amer Zeidan, MBBS

Articles

Dissecting the Current Treatment Landscape in MDS

Dr Zeidan on Classification and Treatment Updates in MDS

Dr Zeidan on Imetelstat in Lower-Risk MDS