Non-Hodgkin Lymphoma

Non-Hodgkin Lymphoma (NHL) usually starts with abnormal proliferation of B lymphocytes, T lymphocytes, or natural killer cells in lymphoid tissues. NHLs can arise from lymphocytes at various developmental stages and the disease characteristics depend on the cell of origin. Hence, NHLs represent a highly heterogeneous group of lymphoid malignancies, with variable frequency, epidemiology, biology, genetic abnormalities, clinical course, and outcomes.

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NHL can be divided into two prognostic groups. Indolent subtypes grow and spread slowly, with patients displaying few signs and symptoms. Indolent NHLs have a relatively good prognosis with a median survival up to 20 years, but they usually are incurable in advanced clinical stage. Aggressive subtypes grow and spread rapidly. Patients may have severe symptoms, but a substantial number can be cured with intensive combination chemotherapy regimens. NHL is the most frequent hematologic malignancy in Europe, causing significant morbidity and mortality in both adults and children.

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Key questions

By gathering data from multiple clinical trials, we can obtain a sufficient sample size to link molecular characteristics to clinical outcomes, thus providing insight in the molecular signatures of this heterogeneous group of malignancies and potentially revealing novel drug targets. In the future, this should lead to more efficient (personalized) treatments. Examples of key questions that HARMONY will address for NHL are:

Which molecular characteristics can predict disease course and drug response? For instance, T cell lymphoma usually is highly aggressive, but it displays significant clinical and molecular heterogeneity.

• HARMONY would like to characterize the molecular landscape of this NHL subtype and link this to disease course and drug response. This may help identify patients eligible for new therapeutic strategies as well as result in putative novel drugs targets.

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Which biomarkers can be used to assess drug response?

• New methods such as metabolic imaging (PET-CT) and minimal residual disease (MRD) monitoring need to be further standardized and validated. For instance, patients with mantle cell lymphoma who achieve MRD negativity seem to have a significantly better outcome than patients who remain MRD-positive, so this may be used to decide on the follow-up strategy.

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What are the most important unmet needs in patient care for specific subtypes of NHL?

• For instance, diffuse large B-cell lymphoma (DLBL, the most common subtype of NHL) is a particularly aggressive subtype that can only be cured in approximately 50% of patients. The major challenge in DLBCL is to improve survival of patients with refractory disease or patients who relapse early in the course of the lymphoma. Follicular lymphoma, on the other hand, is the most common type of indolent NHL. It grows very slowly and many patients receive multiple lines of therapy, causing adverse effects that impair their quality of life.

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NHL Features

• Type of malignant cells: B lymphocytes, T lymphocytes, or natural killer cells;
• Tissue of origin: lymphoid tissues;
• Clinical symptoms: symptoms vary with NHL subtype; the most common subtype (DLBCL) is characterized by lymph node swelling, fever, night sweats, weight loss, and fatigue;
• Five-year survival in Europe: > 60%, with large variation between NHL subtypes;
• Incidence in Europe: age-adjusted incidence of approximately 12 per 100,000;
• Age at diagnosis: occurs in both adults and children, with typical patient characteristics depending on NHL subtype;
• Relevant outcomes: progression-free survival, quality of life (in particular for indolent forms).

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HARMONY Leadership: NHL

• Gilles Salles, LYSA, The Lymphoma Scientific Association, France
• Martin Dreyling, Ludwig Maximilians Universitaet Munchen, Germany
• Silvia Montoto, Barts Health NHS Trust, United Kingdom

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