Blinatumomab after R-CHOP bridging therapy for patients with Richter transformation: a phase 2 multicentre trial

• Published in: Nature communications 2024-08, Vol.15 (1)
• Main Authors: Guièze, Romain, Ysebaert, Loïc, Roos-Weil, Damien, Fornecker, Luc-Mathieu, Ferrant, Emmanuelle, Molina, Lysiane, Aurran, Thérèse, Clavert, Aline, de Guibert, Sophie, Michallet, Anne-Sophie, Saad, Alain, Drénou, Bernard, Quittet, Philippe, Hivert, Bénédicte, Laribi, Kamel, Gay, Julie, Quinquenel, Anne, Broseus, Julien, Rouille, Valérie, Schwartz, David, Magnin, Benoit, Lazarian, Grégory, Véronèse, Lauren, de Antonio, Marie, Laurent, Camille, Tournilhac, Olivier, Pereira, Bruno, Feugier, Pierre
• Format: Article
• Language: English
• Subjects: Life Sciences
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-51264-2

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 fullanalysis-set was 46% (n = 18), with CR in 14 (36%) patients. The most common treatment-emergent adverse events of all grades in the blinatumomab-safetyset 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.Richter transformation (RT) is defined as the onset of aggressive lymphoma, mostly diffuse large B-cell lymphoma (DLBCL), in patients with chronic lymphocytic leukaemia (CLL). Eighty percent of RT cases are clonally related to the prior CLL and result from a transformation process involving complex genomic events with dramatic lesions, resulting in high mutational load 1 . The outcome of patients with RT is usually very poor. Chemoimmunotherapy (CIT), analogous to the treatment of de novo DLBCL, results in low response rates with a median overall survival (OS) of 6-12 months 2,3 . The combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) remains a