Non-Hodgkin Lymphoma in Young Adults A Prospective UK population-based study of incidence, treatment and outcomes. (ODR1516_460)

***This agreement permits Guy's and St Thomas' NHS Foundation Trust to retain data which was historically disseminated by Public Health England (PHE) for the following study - 'Non-Hodgkin lymphoma (NHL) is the least understood of the haematological malignancies that occur during the transitional ‘young adult’ decade between ages 15 and 25 years'. No further processing beyond that supporting the secure retention of the data is permitted under this Agreement. ***

Non-Hodgkin lymphoma encompasses a spectrum of lymphoid neoplasms that together are the fifth most common malignancy occurring in young adults in the UK. From 1995 to 2006 the English Cancer Registries recorded an average of 120 cases of NHL per year, in 16 to 25-year-olds inclusive, but excluding cases in Scotland and Wales. The aggressive lymphomas, diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL) comprise 60% of the total, followed by anaplastic large cell lymphoma (ALCL) and T-lymphoblastic lymphoma (T-LBL). Other types of NHL occurring at this age, follicular lymphoma and cutaneous T-cell lymphoma, appear to be more indolent than in older adults.

Lymphoma diagnosis has advanced substantially with the advent of molecular and genetic markers. Consequently, the true incidence of the individual NHL types as currently defined is unknown. To compound the uncertainty NHL diagnosis remains difficult, particularly at this age where the relative proportions of aggressive NHL types shift from a childhood to an adult pattern. Cancer registry data for this age record a significant proportion as ‘NHL, not otherwise specified’.

Information about treatment outcome using standard regimens is scanty, in part because this age group has the lowest trial entry outside the very elderly, with only 16% being recruited into available trials. Poor trial entry has been cited as the likely reason for the failure of adolescent and young adult (AYA) patients to benefit from the improvements in cancer survival which have occurred in younger and older patients over the past 10-15 years; the ‘AYA Gap’. Cancer registry mortality data, show worse survival for patients aged 15-24 compared to children, for all lymphomas combined and for DLBCL and lymphoblastic lymphomas.

A widely held explanation for this inferior curability through adolescence is that, in addition to changes in the relative frequency between NHL types, there is a change in biology within individual diseases, leading to greater chemotherapy resistance. An alternative explanation for the poor treatment outcomes is the difference in therapeutic approach used by paediatric and adult oncologists for the most commonly occurring aggressive lymphomas, as seen for older teenagers and young adults with ALL.

There is lack of information on treatment and outcomes specific for this age group. Evidence from Ontario (Canada) has demonstrated that place of treatment, and by inference treatment used, influences the outcome of NHL more than for any other malignancy at this age. All this adds urgency to resolve uncertainty around the interaction of age, biology, and therapy on treatment outcomes for young adults with NHL. A recent review urges for “real time” collection and analysis of treatment and outcome data as the most effective way to form hypotheses and evolve treatment strategies. Not only is this a rapid way to provide immediate patient benefit through optimising treatments, it is also better for early identification of toxicities and late effects than more traditional retrospective analysis. Others have highlighted the need for tissue samples to be made available for detailed biological analysis to improve treatment and outcomes.

The UK, with its young adult cancer treatment network, is in a unique position to collect national population-based data on NHL diagnosis, treatment and outcome to fill this void. Our study design will provide the basis to improve clinical care, as well as set the agenda for future research into this complex group of young adult tumours.

Study Aims

1. To establish the incidence of the different subtypes of non-Hodgkin lymphoma (NHL), defined by currently accepted diagnostic criteria, in older teenagers and young adults in the UK.

2. To document treatment regimens being used and related outcomes for each NHL type in a prospective three-year cohort, as a scoping study to inform future treatment recommendations and to inform rational clinical trial design.

3. To establish a diagnostic tissue resource, with linked clinical data, for future study.

Study population:

The study will capture diagnosis and treatment data for all patients with NHL diagnosed between their 15th and 30th birthdays in England, Wales, and Scotland over a 3-year period (2015-2017) with clinical outcomes collected for a minimum 2 years following diagnosis. The data held under this Agreement covers those diagnosed in England only.

While the primary target age is 16 to 24 years inclusive, we will extend the age range to include 15 to 29 years inclusive, to encompass fully the period of biological transition. This also matches the US SEER incidence and survival statistics, 1975-2000. Based on registry data, over 3 years we estimate that we shall recruit 400 patients aged 16 to 24 years, and 650 patients aged 15 to 29 years inclusive. NHL disease types: All diseases classified as non-Hodgkin Lymphoma will be included.

***This agreement permits Guy's and St Thomas' NHS Foundation Trust to retain data which was historically disseminated by Public Health England (PHE) for the following study - 'Non-Hodgkin lymphoma (NHL) is the least understood of the haematological malignancies that occur during the transitional ‘young adult’ decade between ages 15 and 25 years'. No further processing beyond that supporting the secure retention of the data is permitted under this Agreement. ***

Three sources of information were used to identify patients:

i) British Lymphoma Pathology Group (BLPG). For early identification of patients, optimal for prospective treatment data collection, we have sought support from the BLPG, whose members review >90% of all NHL cases in the UK to make or confirm the diagnosis. The group members are supportive in principle of individually notifying the study co-coordinator when they identify a new patient. The BLPG, as an organisation, will encourage but not coordinate participation.

ii) Principal Treatment Centre TYA MDTs. The clinical teams at all Principal and larger Designated TYA Centres will be asked to notify new patients to the study coordinator at diagnosis.

iii) Public Health England National Cancer Registration Service (for which this agreement covers)

Public Health England provided information on all reported cases of NHL within the study age range (England and Wales), to capture those patients not otherwise identified. This may be particularly important for patients diagnosed at age 25 and older.

Not stated in the register.

This research will improve understanding of NHL in this age group, help identify the most effective treatments for each NHL subtype, inform the design of future clinical trials, and lead to more young people with NHL being cured with toxicity-free long term survival.

Not stated in the register.