Dr Zeidan on Imetelstat in Lower-Risk MDS

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 SF3B1, TET2, DNMT3A, and ASXL1 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.

Disclosures: 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.