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Each year, more than 400,000 people worldwide develop tumours of the lymphatic system (lymphoma), and around half that number die from the disease. Better treatments are especially being sought for non-Hodgkin’s lymphoma — the incidence of which is climbing but for which successful treatments are elusive. This Outlook explores research on the origins, diagnosis and treatment of the complex group of cancers that constitutes lymphoma.
This Nature Outlook is editorially independent. It is produced with third party financial support. About this content.
A therapeutic approach in which a person’s immune cells are genetically recoded to enable them to target their cancerous cousins is helping people whose disease is beyond the reach of existing treatments.
F. Hoffmann-La Roche Ltd (Roche) has a rich history of antibody therapies to treat cancers (malignancies) that affect B cells (a type of white blood cell), including non-Hodgkin lymphoma and chronic lymphocytic leukaemia. While dependent on the type of cancer and the stage when the cancer is diagnosed, the outcomes for patients with B-cell malignancies are generally poor and require further improvement.
F. Hoffmann-La Roche Ltd ( Roche) was founded in Basel, Switzerland, in 1896. Since then, Roche has grown into one of the world's leading healthcare companies. With over 100 years of experience, we have driven progress and innovation in healthcare and pride ourselves as being pioneers in the development of new treatments for cancer.
Recent genomic and transcriptomic analyses of diffuse large B cell lymphoma (DLBCL) have provided important new insights into the heterogeneous biology of this disease. The findings provide opportunities to improve treatment strategies, although considerable work is needed to establish and optimize the clinical applicability and utility of molecular classifications of DLBCL.
Response criteria for disease assessment have important therapeutic and prognostic implications in clinical trials and in routine clinical practice. The Lugano classification has been used widely for evaluation of the response of patients with lymphoma to treatment, although the alternative Response Evaluation Criteria In Lymphoma 2017 (RECIL 2017) classification was recently proposed; these criteria are compared herein.
Cell-based immunotherapies are showing great promise in the treatment of even the most treatment-refractory of haematological malignancies. Herein, Jennifer Brudno and James Kochenderfer review the results obtained to date with CAR-T-cell therapies for lymphoma. They also discuss what has been learned regarding the limitations of CAR-T-cell therapies and areas for improvement relating to toxicity management, the design of CAR-T-cell products, conditioning regimens, and combination therapies.
The treatment landscape for lymphoma has become crowded, requiring efficient prioritization for expedited drug development. New challenges include the optimal duration of therapy, as well as the need to balance cost, benefit, and late-onset toxicity. Herein, the authors overview of the most-promising agents in clinical development for the treatment of lymphoma, and provide expert opinion on new strategies to streamline drug development as well as approaches for patient selection and for incorporating new end points into clinical trials.
This Review discusses the mutational landscape and evolution of follicular lymphoma. Deciphering the earliest initiating lesions and the molecular alterations leading to disease progression might help identify the most relevant targets for therapy of these tumours.
Pule and colleagues identify the TCR β-chain constant region as a new target for chimeric antigen receptor (CAR) T cells in treatment of T cell cancers while potentially preserving a healthy T cell repertoire. They demonstrate that anti-TCRB1 CAR T cells eliminate cancerous TCRB1+ T cells while sparing nearly one-third of normal TCRB2+ T cells.
Accurate detection and monitoring of treatment responses is an essential element of the management of patients with lymphoma. In this Perspectives, the authors describe the evolution of lymphoma staging criteria and highlight unaddressed questions, which, if answered, will substantially improve the management of patients with lymphoma.
Immune-checkpoint inhibitors are revolutionizing the treatment of many types of solid cancer. Expression of the inhibitory immune-checkpoint proteins programmed cell-death 1 (PD-1) and its ligands (PD-L1 and PD-L2) are frequently detected in haematological malignancies, and agents targeting these proteins have activity in such diseases, notably Hodgkin lymphoma. Herein, the current evidence supporting the roles of PD-1–PD-L1 blockade in the treatment of various B-cell malignancies is reviewed.
Several novel strategies have harnessed the ability of T cells to target cancer cells. Each treatment approach is based on unique platforms that should encourage development of further therapeutic agents in the future. The authors describe the background and development of distinct immunotherapy platforms, summarize the scientific advances in understanding the mechanism of action of each therapy, and discuss future strategies to improve these immunotherapies through enhanced engineering, biomarker selection, and mechanism-based combination regimens.