B72: Single arm NCRI feasibility phase II study of CHOP in combination with ofatumumab in induction and maintenance for patients with newly diagnosed Richter’s syndrome

Toby Eyre1,Ruth Clifford1,Adrian Bloor11,Lucy Boyle2,Maite Cabes1,Graham P Collins1,Stephen Devereux7,George Follows3,Christopher P Fox4,John Gribben5,Chris S Hatton1,Peter Hillmen6,Tim J Littlewood1,Helen McCarthy8,Jim Murray10,Andrew R Pettitt9,Elizabeth Soilleux1,Sharon B Love2,Corran Roberts2,Anna Schuh1,2

1Oxford University Hospitals NHS Trust, Oxford, UK,2University of Oxford, Oxford, UK,3Addenbrooke’s Hospital NHS Trust, Cambridge, UK,4Nottingham University Hospitals NHS Trust, Nottingham, UK,5Barts & the London School of Medicine & Dentistry, London, UK,6University of Leeds, Leeds, UK,7Kings College Hospital, London, UK,8Royal Bournemouth Hospital, Bournemouth, UK,9Royal Liverpool and Broadgreen University Hospitals National Health Service Trust, Liverpool, UK,10Queen Elizabeth Hospital, Birmingham, UK,11The Christie Hospital NHS Trust, Manchester, UK

Presenting date: Tuesday 3 November
Presenting time: 13.10-14.00

Background

Transformation of Chronic Lymphocytic Leukaemia (CLL) to diffuse large B cell lymphoma (DLBCL) (Richter's syndrome, RS) is rare (2-15%) but associated with a very poor prognosis. Ofatumumab (O) is a fully human anti-CD20 IgG1? monoclonal antibody that targets a B-cell epitope which is distinct from that targeted by rituximab. We evaluate the safety, feasibility and activity of CHOP-O in induction and maintenance for newly diagnosed RS. The primary objective was overall response rate (ORR) after 6 cycles of CHOP-O.

Method

This single arm, multi-centre, non-randomised phase II NCRI feasibility study recruited 43 patients with newly diagnosed RS across 10 UK centres. Eligibility included: ?18 years, PS 0-3, known or newly diagnosed CLL and newly diagnosed, untreated RS. Eligible patients received CHOP-O for 6 cycles, followed by 6 cycles of O-maintenance (8 weekly). Histology results were reviewed locally for study inclusion to replicate ‘real life'.

Results

43 patients were recruited of which 36 patients are currently evaluable (1 pending). 73% were over 60 years, and most were male. Over half of patients had received a fludarabine and cyclophosphamide based regimen as prior treatment for CLL. Baseline PET CT was performed in 42% of enrolled patients.


The ORR to induction was moderate. 66% responded (PR or CR) after four cycles of CHOP-O, although this reduced to 44% ORR (CR 25%, PR 19%) at the end of induction.


CHOP-O was typically well tolerated. 15 episodes of neutropenic fever were reported and grade 3-4 neutropenia was noted on 14 occasions. A single SAE as the result of an ofatumumab-induced infusion reaction was reported. There were no treatment related deaths.

Conclusion

This study proved that it is feasible to perform clinical trials in RS and answer important questions. It is likely that CHOP-O does not considerably improve outcomes compared with R-CHOP in RS.