Research to identify reasons behind poor response to treatment for blood cancer patients

Targeted and more effective treatment options for patients with blood cancers are the aim of a major, five-year collaborative project between researchers at the University of York, the Haematological Malignancy Diagnostic Service (HMDS) at Leeds Teaching Hospitals NHS Trust, and the Universities of Cambridge and Southampton. Researchers at the Department of Health Sciences’ Epidemiology & Cancer Statistics Group (ECSG), led by Dr Simon Crouch, have received part of £1m funding from the Leukaemia & Lymphoma Research charity to investigate why some patients with diffuse large B-cell lymphoma (DLBCL) fail to respond to standard treatment.

DLBCL is by far the most common aggressive lymphoma in the UK, currently treated by an antibody-combining chemotherapy regimen, commonly known as R-CHOP. Despite dramatically improved survival outcomes for the majority of such patients, there is a significant minority of treatment recipients (up to 30%) who show either no response, only partial response or relapse after the initial response. Importantly, disease resistant to R-CHOP also responds poorly to any other currently available treatments, thus accounting for the vast majority of lymphoma-related deaths. Coupled with issues of cost effectiveness (the significant cost of the repeated administration of complete R-CHOP courses), this variable response of the disease to available treatments imposes an acute clinical dilemma with fundamental implications both for patient care and treatment commissioning.

The proposed programme of work aims to design and test new therapeutic strategies for this sub-group of DLBCL patients by developing multi-layered prognostic models based on the molecular and genetic characteristics of the disease.

The project builds on on-going research collaborations between all institutions involved. It will uniquely combine complete treatment and clinical follow-up data from more than 4,000 patients, recruited from both a major phase III clinical trial (REMoDL-B) and a population-based cohort (ECSG’s Haematological Malignancy Research Network [HMRN]). Results will be incorporated into ECSG’s growing portfolio of research projects focusing on facilitating greater patient choice on available and offered treatments in haemato-oncology in the context of individual patient need and cost effectiveness for the NHS.

“The heterogeneity of DLBCL in terms of clinical course, immunophenotype and genetic abnormalities has consistently been shown to hold prognostic significance, although consensus on disease sub-classification is still developing. By comprehensively investigating the association of a series of biomarkers with specific clinical and pathological parameters, we aim to assess their utility in predicting treatment response, and to progress to develop and validate optimal prognostic models targeted to individual patient needs.”
Dr Simon Crouch, Epidemiology & Cancer Statistics Group