Blinatumomab after R-CHOP bridging therapy for patients with Richter transformation: a phase 2 multicentre trial
Richter transformation (RT) is an aggressive lymphoma occurring in patients with chronic lymphocytic leukaemia. Here we investigated the anti-CD3/anti-CD19 T-cell-engager blinatumomab after R-CHOP (i.e. rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with untreated RT of diffuse large B-cell lymphoma histology (NCT03931642). In this multicentre phase 2 study, patients without complete response (CR) after two cycles of R-CHOP were eligible to receive an 8-week blinatumomab induction via continuous vein infusion with stepwise dosing until 112 μg/day. The primary endpoint was the CR rate after blinatumomab induction and secondary endpoint included safety, response duration, progression-free and overall survival. Thirty-nine patients started the first cycle of R-CHOP, 25 of whom received blinatumomab. After blinatumomab induction, five (20%) patients achieved CR, four (16%) achieved partial response, and six (24%) were stable. Considering the entire strategy, the overall response rate in the full-analysis-set was 46% (n = 18), with CR in 14 (36%) patients. The most common treatment-emergent adverse events of all grades in the blinatumomab-safety-set included fever (36%), anaemia (24%), and lymphopaenia (24%). Cytokine release syndrome (grade 1/2) was observed in 16% and neurotoxicity in 20% of patients. Blinatumomab demonstrated encouraging anti-tumour activity (the trial met its primary endpoint) and acceptable toxicity in patients with RT.
Authors
- Sophie de Guibert (ORCID: https://orcid.org/0000-0003-0418-7266)
- Grégory Lazarian (ORCID: https://orcid.org/0000-0002-4315-3440)
- Julien Broséus (ORCID: https://orcid.org/0000-0002-6689-4006)
- Loïc Ysebaert (ORCID: https://orcid.org/0000-0003-4102-7261)
- Bénédicte Hivert (ORCID: https://orcid.org/0009-0007-2954-6743)
- Romain Guièze (ORCID: https://orcid.org/0000-0001-7563-580X)
- Kamel Laribi (ORCID: https://orcid.org/0009-0004-8177-7870)
- Philippe Quittet (ORCID: https://orcid.org/0000-0003-2324-5660)
- Lauren Véronèse (ORCID: https://orcid.org/0000-0002-4414-7974)
- David A. Schwartz (ORCID: https://orcid.org/0000-0002-7486-8545)
- Olivier Tournilhac (ORCID: https://orcid.org/0000-0002-9438-621X)
- Anne‐Sophie Michallet (ORCID: https://orcid.org/0000-0002-4256-8126)
- Julie Gay (ORCID: https://orcid.org/0009-0006-8923-6010)
- Valérie Rouille
- Luc-Mathieu Fornecker
- Bernard Drénou (ORCID: https://orcid.org/0000-0002-2175-6785)
- Bruno Pereira (ORCID: https://orcid.org/0000-0001-6102-4530)
- Thérèse Aurran
- Anne Quinquenel (ORCID: https://orcid.org/0000-0002-3666-3442)
- Aline Clavert (ORCID: https://orcid.org/0000-0003-1270-848X)
- Damien Roos‐Weil (ORCID: https://orcid.org/0000-0002-7767-755X)
- Camille Laurent (ORCID: https://orcid.org/0000-0002-5375-7512)
- Benoît Magnin
- Marie De Antonio (ORCID: https://orcid.org/0000-0001-5114-0546)
- Emmanuelle Ferrant
- Alain Saad
- Lysiane Molina
- Pierre Feugier
Institutions
- Inserm (FR)
- Université Clermont Auvergne (FR)
- Centre Hospitalier Universitaire de Grenoble (FR)
- Institut Pprime (FR)
- Centre Hospitalier Universitaire de Toulouse (FR)
- Sorbonne Université (FR)
- Institut de Cancérologie Strasbourg (FR)
- Centre Hospitalier Universitaire de Montpellier (FR)
- Acute Leukemia French Association (FR)
- Centre Hospitalier de Béziers (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Centre Hospitalier Régional et Universitaire de Nancy (FR)
- Hospices Civils de Lyon (FR)
- University of Clermont Auvergne (FR)
- Centre Léon Bérard (FR)
- Centre Hospitalier Universitaire de Reims (FR)
- Centre Hospitalier Universitaire d'Angers (FR)
- Hôpital Lyon Sud (FR)
- Centre Hospitalier de Mulhouse (FR)
- Pitié-Salpêtrière Hospital (FR)
- Centre Hospitalier du Mans (FR)
- Centre Hospitalier de la Côte Basque (FR)
- Centre Hospitalier Universitaire de Clermont-Ferrand (FR)
- Hôpital Avicenne (FR)
- Groupe Hospitalier de l'Institut Catholique de Lille (FR)
- Clermont Université (FR)
- Institut Paoli-Calmettes (FR)
- Centre Hospitalier Universitaire de Rennes (FR)
- Nutrition-Génétique et Exposition aux Risques Environnementaux (FR)
- Université de Strasbourg (FR)
- Université Grenoble Alpes (FR)
- Université de Lorraine (FR)
- Université de Reims Champagne-Ardenne (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-08-09
- DOI
- https://doi.org/10.1038/s41467-024-51264-2
- Citations
- 10
- Primary Topic
- Chronic Lymphocytic Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 4.38
Funders
- Amgen