NCRI phase II study of CHOP in combination with ofatumumab in induction and maintenance in newly diagnosed Richter syndrome

Richter syndrome (RS) is associated with chemotherapy resistance and a poor historical median overall survival (OS) of 8-10months. We conducted a phase II trial of standard CHOP-21 (cyclophosphamide, doxorubicin, vincristine, prednisolone every 21d) with ofatumumab induction (Cycle 1: 300mg day 1, 1000mg day 8, 1000mg day 15; Cycles 2-6: 1000mg day 1) (CHOP-O) followed by 12months ofatumumab maintenance (1000mg given 8-weekly for up to six cycles). Forty-three patients were recruited of whom 37 were evaluable. Seventy-three per cent were aged >60years. Over half of the patients received a fludarabine and cyclophosphamide-based regimen as prior CLL treatment. The overall response rate was 46% (complete response 27%, partial response 19%) at six cycles. The median progression-free survival was 62months (95% confidence interval [CI] 49-140months) and median OS was 114months (95% CI 64-256months). Treatment-naive and TP53-intact patients had improved outcomes. Fifteen episodes of neutropenic fever and 46 non-neutropenic infections were observed. There were no treatment-related deaths. Seven patients received platinum-containing salvage at progression, with only one patient obtaining an adequate response to proceed to allogeneic transplantation. CHOP-O with ofatumumab maintenance provides minimal benefit beyond CHOP plus rutuximab. Standard immunochemotherapy for RS remains wholly inadequate for unselected RS. Multinational trials incorporating novel agents are urgently needed.