Single arm NCRI phase II study of CHOP in combination with Ofatumumab in induction and maintenance for patients with newly diagnosed Richter's syndrome

BMC Cancer
Toby A EyreSusan J Dutton

Abstract

Transformation of B-cell chronic lymphocytic leukaemia (B-CLL) to diffuse large B cell lymphoma (DLBCL) (Richter's syndrome (RS)) is a rare (2-15% of patients) but catastrophic complication of B-CLL. Dose-intense chemotherapy regimens investigated in small single institution trials, but with the exception of bone marrow transplantation for a minority of patients, little has improved the median overall survival of patients with RS beyond eight months. Patients are often elderly, immunosuppressed, possess co-morbidities and have a deteriorating performance status. TP53 disruption is a common molecular abnormality noted in RS and contributes to the tumour's chemotherapy resistance. Ofatumumab is a fully human anti-CD20 monoclonal IgG1κ antibody that targets a unique epitope on B lymphocytes. It has displayed increased binding affinity and a longer dissociation time when compared to rituximab resulting in improved complement dependent cellular cytotoxicity (CDCC); a mechanism with the potential to overcome apoptosis-resistance in TP53 disruption. Given the prevalence of TP53 disruption in RS, Ofatumumab was considered a relatively non-toxic agent with a sound rationale to test in a prospective multicentre trial as an adjunct to CHO...Continue Reading

References

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Citations

Nov 15, 2015·Expert Opinion on Drug Safety·Anna Korycka-WołowiecTadeusz Robak
Feb 3, 2016·Current Hematologic Malignancy Reports·Candida Vitale, Alessandra Ferrajoli
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Aug 30, 2017·Future Oncology·Zar Ni Soe, David Allsup
Oct 5, 2021·British Journal of Haematology·Toby A EyreUNKNOWN Haemato-Oncology Task Force of the British Society for Haematology

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Methods Mentioned

BETA
biopsy
contraception

Clinical Trials Mentioned

NCT01171378

Software Mentioned

OpenClinica

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