Glofitamab Combined With Pola-R-CHP or R-CHOP as First Therapy in Younger Patients With High-Risk Large B-Cell Lymphoma: Results From the COALITION Study
Mené sur 80 patients atteints d'un lymphome à grandes cellules B à haut risque de récidive (âge médian : 58 ans ; durée médiane de suivi : 20,7 mois), cet essai de phase II évalue la toxicité et l'efficacité, du point de vue du taux de réponse, du glofitamab en combinaison avec une chimiothérapie de première ligne de type Pola-R-CHP ou de type R-CHOP
Purpose: Improved outcomes are needed for patients with high-risk (HR) large B-cell lymphoma (LBCL) who have <50% chance of cure with first-line (1L) R-CHOP chemotherapy. Patients with high burden or rapid progression are often excluded from 1L trials due to screening requirements. We report the investigator-initiated, phase II COALITION trial of the CD20xCD3 bispecific antibody glofitamab combined with R-CHOP or Pola-R-CHP in younger patients with HR features, designed to minimize time between diagnosis and treatment.
Methods: Patients age ≤65 years with LBCL and at least one HR feature (international prognostic index [IPI] ≥3, National Comprehensive Cancer Network-IPI ≥4, or rearrangements of MYC and BCL2 and/or BCL6) received one cycle of R-CHOP and were randomly assigned to five cycles of Glofit-Pola-R-CHP (n = 40) or Glofit-R-CHOP (n = 40), and two cycles of glofitamab consolidation. Enrollment occurred before or after a cycle of R-CHOP. The primary objective was safety and treatment deliverability. Secondary end points included response rates and survival.
Results: Eighty evaluable patients with a median age of 58 years and total metabolic tumor volume of 842 cm3 were included and began treatment a median of 14 days from diagnosis. Over 95% of patients completed all therapy and the median relative dose intensity was >94%. Cytokine release syndrome was observed in 21% of patients, all ≤grade 2 and manageable. Overall and complete response rates were 100% and 98%, respectively. At 20.7-month median follow-up, the estimated 2-year progression-free survival and overall survival were 86% and 92%, respectively.
Conclusion: The combination of glofitamab with R-CHOP or Pola-R-CHP is deliverable and results in high rates of durable response in this population of younger patients with high-burden, HR LBCL, supporting its ongoing exploration as a 1L treatment.
Journal of Clinical Oncology , résumé, 2025