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