Zanubrutinib in combination with R-CHOP for previously untreated mcd type of Diffuse large b-cell lymphoma (DLBCL).

Abstract

Diffuse large B‐cell lymphoma (DLBCL) is the most common of the non‐Hodgkin's lymphomas.Whilst the majority of patients will respond well to conventional treatment (R‐CHOP ‐rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone), a significantnumber of patients lymphoma will not respond to initial therapy or their disease willreturn after completion of therapy. In a number of B‐cell diseases an enzyme called,Bruton tyrosine kinase (BTK) prevents death of tumour cells, including in DLBCL.Acalabrutinib is an orally active BTK‐inhibitor and it is thought that stopping BTK beingactivated may help in treating B‐cell diseases. It is hypothesised that the addition ofAcalabrutinib to standard R‐CHOP immunochemotherapy may improve outcomes of patients withDLBCL.REMoDL‐A is a randomised, phase II, open label, multicentre study that will be open in upto 50 centres. Up to 553 patients (453 randomised) will be recruited.Following informed consent all patients will receive 1 cycle of conventional R‐CHOPchemotherapy. At the same time the diagnostic pathology block will be sent for molecularprofiling by the Haematological Malignancy Diagnostic Service (HMDS). The delivery of thefirst cycle of R‐CHOP will allow a sufficient interval for real time determination ofmolecular phenotype. Patients whose biopsies yield sufficient tumour material forprofiling will be randomised 2:1 in favour of the experimental arm (R‐CHOP +acalabrutinib).The primary objective will be to establish if combining acalabrutinib with R‐CHOPimproves efficacy, compared to R‐CHOP alone, for the treatment of previously untreatedpatients with DLBCL to a degree that justifies further development of this approach.