Details

Autor(en) / Beteiligte

• Kiladjian, Jean-Jacques
• Harrison, Claire
• Mesa, Ruben A.
• Al-Ali, Haifa K.
• Mascarenhas, John
• Sanabria, Fabian
• Bürki, Julie Vienne
• Bengoudifa, Bourras-Rezki
• Passamonti, Francesco

Titel

MPN-346 INDEPENDENCE: Enrolling Phase III Trial to Study the Efficacy and Safety of Luspatercept versus Placebo in Patients With Myelofibrosis on JAK2 Inhibitor (JAK2i) Therapy Requiring Red Blood Cell Transfusions (RBCTs)

Ist Teil von

• Clinical lymphoma, myeloma and leukemia, 2023-09, Vol.23, p.S390-S390

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2023

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Many patients with myelofibrosis develop anemia and RBCT dependence, associated with poor prognosis. Luspatercept is a first-in-class erythroid maturation agent approved for treatment of anemia in specific RBCT-dependent patients with b-thalassemia/myelodysplastic syndromes. In a phase II trial (NCT03194542), 26.3% of RBCT-dependent, ruxolitinib-treated patients with myelofibrosis achieved ≥12 weeks of RBCT independence (RBC-TI) with luspatercept (Gerds AT, et al. American Society Clinical Oncology 2023; Poster 7016). INDEPENDENCE (NCT04717414) is a Phase III, double-blind trial to determine the efficacy of luspatercept versus placebo for treatment of anemia in patients with MPN-associated myelofibrosis on concomitant JAK2i therapy requiring RBCT. Eligible patients (aged ≥18 years; requiring 4-12 RBC units/12 weeks; ≥32 weeks concomitant JAK2i therapy /≥16 weeks stable daily dose; no anemia from other causes or medications with hematopoietic effects ≤8 weeks before randomization) will be randomized 2:1 to luspatercept (starting at 1.33 mg/kg; titration up to 1.75 mg/kg) subcutaneously, or placebo, every 3 weeks. Stratification factors include baseline RBCT and DIPSS score. Treatment phase: 24-week core period and disease response assessment (Day 169). Best supportive care is allowed. Clinical benefit (CB): RBC-TI for any consecutive ≥12-week period in weeks 1–24, RBCT burden reduction by ≥50% and by ≥4 RBC units for ≥12 weeks in weeks 1–24, or incomplete response duration (RBC-TI for ≥4 weeks immediately up to end of Week 24). Patients with CB can continue luspatercept until loss of benefit, progression to acute myelogenous leukemia, unacceptable toxicity, consent withdrawal, or meeting other discontinuation criteria. Patients without CB (Day 169) can be unblinded and those on placebo can cross over to open-label luspatercept. Planned post-treatment follow-up period: 5-years post-first dose or 3 years post-last dose. As of May 10, 2023, 53% (164/309) of planned patients have been enrolled globally across 21 countries and 150 activated sites. Primary endpoint: proportion of patients who become RBCT-free over any consecutive 12-week period starting between randomization and Week 24. MPN (International congress on Myeloproliferative Neoplasm) 2022 (P116) and DGHO (Deutschen, Österreichischen und Schweizerischen Gesellschaften für Hämatologie und Medizinische Onkologie) 2022 (P911). Bristol Myers Squibb