Blinatumomab after R-CHOP bridging therapy for patients with Richter transformation: a phase 2 multicentre trial
Romain Guièze, Loïc Ysebaert, Damien Roos‐Weil, Luc-Mathieu Fornecker, Emmanuelle Ferrant, Lysiane Molina, Thérèse Aurran, Aline Clavert, Sophie de Guibert, Anne‐Sophie Michallet, Alain Saad, Bernard Drénou, Philippe Quittet, Bénédicte Hivert, Kamel Laribi, Julie Gay, Anne Quinquenel, Julien Broséus, Valérie Rouille, David A. Schwartz, Benoît Magnin, Grégory Lazarian, Lauren Véronèse, Marie De Antonio, Camille Laurent, Olivier Tournilhac, Bruno Pereira, Pierre Feugier
Abstract
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.