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), p.6822-8, Article 6822
• 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: 631/250/251; 692/4028/67/1990; Adult; Aged; Aged, 80 and over; Anemia; Antibodies, Bispecific - administration & dosage; Antibodies, Bispecific - adverse effects; Antibodies, Bispecific - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; B-cell lymphoma; CD19 antigen; CD3 antigen; Chronic lymphocytic leukemia; Cyclophosphamide; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Cyclophosphamide - therapeutic use; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Doxorubicin - therapeutic use; Female; Histology; Humanities and Social Sciences; Humans; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Life Sciences; Lymphocytes B; Lymphocytes T; Lymphoma; Lymphoma, Large B-Cell, Diffuse - drug therapy; Male; Medical prognosis; Middle Aged; Monoclonal antibodies; multidisciplinary; Neurotoxicity; Patients; Prednisone; Prednisone - administration & dosage; Prednisone - adverse effects; Prednisone - therapeutic use; Rituximab; Rituximab - administration & dosage; Rituximab - adverse effects; Rituximab - therapeutic use; Science; Science (multidisciplinary); Targeted cancer therapy; Treatment Outcome; Vincristine; Vincristine - administration & dosage; Vincristine - adverse effects; Vincristine - therapeutic use
• 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 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. A combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is a commonly used regimen for patients with Richter transformation (RT), an aggressive lymphoma with a poor prognosis. Here the authors report the results of a phase 2 clinical trial of blinatumomab (an anti-CD3/anti-CD19 bispecific T-cell-engager) after R-CHOP bridging therapy for patients with RT.