Background The standard treatment for patients with diffuse large-B-cell lymphoma is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Rituximab, a chimeric monoclonal antibody against the CD20 B-cell antigen, has therapeutic activity in diffuse large-B-cell lymphoma. We conducted a randomized trial to compare CHOP chemotherapy plus rituximab with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. Methods Previously untreated patients with diffuse large-B-cell lymphoma, 60 to 80 years old, were randomly assigned to receive either eight cycles of CHOP every three weeks (197 patients) or eight cycles of CHOP plus rituximab given on day 1 of each cycle (202 patients). Results The rate of complete response was significantly higher in the group that received CHOP plus rituximab than in the group that received CHOP alone (76 percent vs. 63 percent, P=0.005). With a median follow-up of two years, event-free and overall survival times were significantly higher in the CHOP-plus-rit...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa011795

CHOP Chemotherapy plus Rituximab Compared with CHOP Alone in Elderly Patients with Diffuse Large-B-Cell Lymphoma

Purpose Standardized response criteria are needed to interpret and compare clinical trials and for approval of new therapeutic agents by regulatory agencies. Methods The International Working Group response criteria (Cheson et al, J Clin Oncol 17:1244, 1999) were widely adopted, but required reassessment because of identified limitations and the increased use of [ 18 F]fluorodeoxyglucose-positron emission tomography (PET), immunohistochemistry (IHC), and flow cytometry. The International Harmonization Project was convened to provide updated recommendations. Results New guidelines are presented incorporating PET, IHC, and flow cytometry for definitions of response in non-Hodgkin’s and Hodgkin’s lymphoma. Standardized definitions of end points are provided. Conclusion We hope that these guidelines will be adopted widely by study groups, pharmaceutical and biotechnology companies, and regulatory agencies to facilitate the development of new and more effective therapies to improve the outcome of patients with lymphoma. J Clin Oncol 25:579-586. © 2007 by American Society of Clinical Oncology

/pdf/revised-response-criteria-for-malignant-lymphoma-41zde6csg7.pdf

Revised response criteria for malignant lymphoma

PURPOSE: The European Association of Hematopathologists and the Society for Hematopathology have developed a new World Health Organization (WHO) classification of hematologic malignancies, including lymphoid, myeloid, histiocytic, and mast cell neoplasms. DESIGN: Ten committees of pathologists developed lists and definitions of disease entities. A clinical advisory committee (CAC) of international hematologists and oncologists was formed to ensure that the classification would be useful to clinicians. The CAC met in November 1997 to discuss clinical issues related to the classification. RESULTS: The WHO uses the Revised European-American Lymphoma (REAL) classification, published in 1994 by the International Lymphoma Study Group, to categorize lymphoid neoplasms. The REAL classification is based on the principle that a classification is a list of “real” disease entities, which are defined by a combination of morphology, immunophenotype, genetic features, and clinical features. The relative importance of ea...

World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997.

The purpose of this work was to modernize recommendations for evaluation, staging, and response assessment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). A workshop was held at the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland, in June 2011, that included leading hematologists, oncologists, radiation oncologists, pathologists, radiologists, and nuclear medicine physicians, representing major international lymphoma clinical trials groups and cancer centers. Clinical and imaging subcommittees presented their conclusions at a subsequent workshop at the 12th International Conference on Malignant Lymphoma, leading to revised criteria for staging and of the International Working Group Guidelines of 2007 for response. As a result, fluorodeoxyglucose (FDG) positron emission tomography (PET)–computed tomography (CT) was formally incorporated into standard staging for FDG-avid lymphomas. A modification of the Ann Arbor descriptive terminology will be used for ana...

/pdf/recommendations-for-initial-evaluation-staging-and-response-5zfzjttmb3.pdf

Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification

Macrophages are crucial drivers of tumour-promoting inflammation. Tumour-associated macrophages (TAMs) contribute to tumour progression at different levels: by promoting genetic instability, nurturing cancer stem cells, supporting metastasis, and taming protective adaptive immunity. TAMs can exert a dual, yin-yang influence on the effectiveness of cytoreductive therapies (chemotherapy and radiotherapy), either antagonizing the antitumour activity of these treatments by orchestrating a tumour-promoting, tissue-repair response or, instead, enhancing the overall antineoplastic effect. TAMs express molecular triggers of checkpoint proteins that regulate T-cell activation, and are targets of certain checkpoint-blockade immunotherapies. Other macrophage-centred approaches to anticancer therapy are under investigation, and include: inhibition of macrophage recruitment to, and/or survival in, tumours; functional re-education of TAMs to an antitumour, 'M1-like' mode; and tumour-targeting monoclonal antibodies that elicit macrophage-mediated extracellular killing, or phagocytosis and intracellular destruction of cancer cells. The evidence supporting these strategies is reviewed herein. We surmise that TAMs can provide tools to tailor the use of cytoreductive therapies and immunotherapy in a personalized medicine approach, and that TAM-focused therapeutic strategies have the potential to complement and synergize with both chemotherapy and immunotherapy.

/pdf/tumour-associated-macrophages-as-treatment-targets-in-3gdbul5s9u.pdf

Tumour-associated macrophages as treatment targets in oncology

Erratum: Five-year results of brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma (Blood ( 2017) 130, 5 (2709-2717) DOI: 10.1182/blood-2017-05-780049)

Prognostic Value of Baseline Quantitative PET Metrics for Patients with Unfavourable Early Stage Hodgkin Lymphoma Enrolled in the Standard Arm of the EORTC/Lysa/FIL H10 Trial

Andrea Barp, Laurent Gilardin, Vadim Afanasiev, C ecile Delorme, Karine Viala, Sophie Bernard, Pauline Brice, Dimitri Psimaras and Timoth ee Lenglet D epartement de Neurophysiologie, Hôpital de la Piti e-Salpêtri ere, APHP, Paris, France; Service d’Onco-H ematologie, Hôpital SaintLouis, APHP, Paris, France; Institut National de la Sant e et de la Recherche M edicale (INSERM), Unit e Mixte de Recherche en Sant e (UMR S) 1138, Centre de Recherche des Cordeliers, Equipe Immunopathology and Therapeutic Immunointervention, Paris, France; Centre d’Evaluation et Traitement des Neuropathies, Hôpital de la Piti e-Salpêtri ere, APHP, Paris, France; OncoNeuroTox group: Center for investigations of patients with neurological complications after cancer treatment, Hôpitaux universitaires Piti e-Salpêtri ereCharles Foix et Val-de-Grâce, Paris, France

Subacute inflammatory demyelinating polyradiculoneuropathy complicating relapsing Hodgkin lymphoma: another immune-related adverse event of the anti-PD1 therapy?

BACKGROUND. High-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) remain controversial for indolent lymphoma patients. METHODS. The study was designed to evaluate the benefit of this strategy by retrospectively comparing for each patient the event-free survival (EFS) after ASCT with the duration of the disease phase just before the phase including ASCT (ie, the last qualifying phase, LQP). RESULTS. A total of 109 indolent lymphoma (mostly follicular lymphoma) patients were treated with HDT and ASCT. Before ASCT, patients experienced a median of 2 disease phases (range, 1-4). After a median 5-year follow-up from ASCT, overall survival was 67% and EFS was 43%. When each of the 92 patients experiencing recurrence was taken as her/his own control, EFS was longer after ASCT than the duration of LQP (62%, P <.01). During LQP, 86 patients (93%) experienced recurrence in less than 5 years, compared with only 58 (63%) who experienced recurrence in the 5 years after ASCT (P <.01). CONCLUSION. HDT and ASCT can significantly increase EFS in comparison with the duration of the LQP for indolent lymphoma patients and can change disease course. This methodology has been found useful for evaluating new strategies, especially with monoclonal antibodies.

High-dose therapy and autologous stem-cell transplantation can improve event-free survival for indolent lymphoma : A study using patients as their own controls

Pauline Brice

Papers

Erratum: Five-year results of brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma (Blood ( 2017) 130, 5 (2709-2717) DOI: 10.1182/blood-2017-05-780049)

Prognostic Value of Baseline Quantitative PET Metrics for Patients with Unfavourable Early Stage Hodgkin Lymphoma Enrolled in the Standard Arm of the EORTC/Lysa/FIL H10 Trial

Subacute inflammatory demyelinating polyradiculoneuropathy complicating relapsing Hodgkin lymphoma: another immune-related adverse event of the anti-PD1 therapy?

High-dose therapy and autologous stem-cell transplantation can improve event-free survival for indolent lymphoma : A study using patients as their own controls

Fertility preservation before an ABVD protocol: no new evidence to support changing the recommendations