Disease Overview
Hodgkin lymphoma (HL) is an uncommon B‐cell lymphoid malignancy affecting 8500 new patients annually and representing approximately 10.2% of all lymphomas in the United States.
...Diagnosis
HL is composed of two distinct disease entities: classical HL and nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte‐rich HL are subgroups of classical HL.
Risk Stratification
An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography scan, are used to optimize therapy.
Risk‐Adapted Therapy
Initial therapy for HL patients is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved‐field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. Newer agents including brentuximab vedotin are now being incorporated into frontline therapy and these new combinations are becoming a standard of care.
Management of Relapsed/Refractory Disease
High‐dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD‐1 blockade, nonmyeloablative allogeneic transplant or participation in a clinical trial should be considered.
The clinical development of effective cancer immunotherapies, along with advances in genomic analysis, has led to the identification of tumor environmental features that predict for sensitivity to ...immune checkpoint blockade therapy (CBT). Early-phase clinical trial results have demonstrated the remarkable effectiveness of CBT in specific lymphoma subtypes, including classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma. Conversely, CBT has been relatively disappointing in follicular lymphoma and diffuse large B-cell lymphoma. These clinical observations, coupled with important scientific discoveries, have uncovered salient features of the lymphoma microenvironment that correlate with immunotherapy response in patients. For example, classical Hodgkin lymphoma is characterized by an inflammatory environment, genetic alterations that facilitate escape from immune attack, and sensitivity to PD-1 blockade therapy. On the other hand, for lymphomas in which measures of immune surveillance are lacking, including follicular lymphoma and most diffuse large B-cell lymphomas, anti-PD-1 therapy has been less effective. An improved understanding of the immune landscapes of these lymphomas is needed to define subsets that might benefit from CBT. In this article, we describe the immune environments associated with major B-cell lymphomas with an emphasis on the immune escape pathways orchestrated by these diseases. We also discuss how oncogenic alterations in lymphoma cells may affect the cellular composition of the immune environment and ultimately, vulnerability to CBT. Finally, we highlight key areas for future investigation, including the need for the development of biomarkers that predict for sensitivity to CBT in lymphoma patients.
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Disease overview
Hodgkin lymphoma (HL) is an uncommon B‐cell lymphoid malignancy affecting 8480 new patients annually and representing approximately 10% of all lymphomas in the United States.
...Diagnosis
Hodgkin lymphoma is composed of two distinct disease entities: classical HL and nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte‐rich HL are subgroups of classical HL.
Risk stratification
An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography (PET) scan, are used to optimize therapy.
Risk‐adapted therapy
Initial therapy for HL patients is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy, followed by involved‐field radiation therapy. Patients with advanced stage disease receive a longer course of chemotherapy, often without radiation therapy. However, newer agents including brentuximab vedotin and anti‐PD‐1 antibodies are now being incorporated into frontline therapy.
Management of relapsed/refractory disease
High‐dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD‐1 blockade, non‐myeloablative allogeneic transplant or participation in a clinical trial should be considered.
Despite an extensive immune infiltrate that is recruited to the tumor by malignant Reed-Sternberg cells in Hodgkin lymphoma, the antitumor immune response is ineffective and unable to eradicate the ...malignant cells. The ineffective immune response is in part due to PD-1 signaling that renders intratumoral immune cells anergic. Reed-Sternberg cells have been shown to upregulate expression of the PD-1 ligands, PD-L1 and PD-L2, due to either genetic alterations at chromosome 9p24.1 or Epstein-Barr virus infection, and these ligands suppress the function of PD-1
intratumoral T cells. Blockade of PD-1 signaling has proven to be a highly successful therapeutic approach, and the use of the anti-PD-1 mAb nivolumab recently received accelerated approval by the FDA for patients with classical Hodgkin lymphoma that has relapsed or progressed after autologous stem cell transplant and posttransplantation brentuximab vedotin. Initial clinical trials using nivolumab in this patient population resulted in high response rates that were durable. Adverse events associated with nivolumab included immune-mediated adverse reactions and infusion reactions, but these were well tolerated, allowing for continued nivolumab administration. Clinical trials are now in progress to test the use of nivolumab in combination with standard chemotherapy or with novel agents with a goal of improving the outcome of patients with Hodgkin lymphoma.
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Hodgkin lymphoma is a rare B-cell malignant neoplasm affecting approximately 9000 new patients annually. This disease represents approximately 11% of all lymphomas seen in the United States and ...comprises 2 discrete disease entities--classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma. Within the subcategorization of classical Hodgkin lymphoma are defined subgroups: nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich Hodgkin lymphoma. Staging of this disease is essential for the choice of optimal therapy. Prognostic models to identify patients at high or low risk for recurrence have been developed, and these models, along with positron emission tomography, are used to provide optimal therapy. The initial treatment for patients with Hodgkin lymphoma is based on the histologic characteristics of the disease, the stage at presentation, and the presence or absence of prognostic factors associated with poor outcome. Patients with early-stage Hodgkin lymphoma commonly receive combined-modality therapies that include abbreviated courses of chemotherapy followed by involved-field radiation treatment. In contrast, patients with advanced-stage Hodgkin lymphoma commonly receive a more prolonged course of combination chemotherapy, with radiation therapy used only in selected cases. For patients with relapse or refractory disease, salvage chemotherapy followed by high-dose treatment and an autologous stem cell transplant is the standard of care. For patients who are ineligible for this therapy or those in whom high-dose therapy and autologous stem cell transplant have failed, treatment with brentuximab vedotin is a standard approach. Additional options include palliative chemotherapy, immune checkpoint inhibitors, nonmyeloablative allogeneic stem cell transplant, or participation in a clinical trial testing novel agents.
Disease Overview
Hodgkin lymphoma (HL) is an uncommon B‐cell lymphoid malignancy affecting 8540 new patients annually and representing approximately 10% of all lymphomas in the United States.
...Diagnosis
HL is composed of two distinct disease entities: classical HL and nodular lymphocyte‐predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte‐rich HL are subgroups of classical HL.
Risk Stratification
An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography scan, are used to optimize therapy.
Risk‐Adapted Therapy
Initial therapy for HL patients is based on the histology of the disease, the anatomical stage, and the presence of poor prognostic features. Patients with early‐stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved‐field radiation therapy, while those with advanced‐stage disease receive a longer course of chemotherapy, often without radiation therapy. However, newer agents, including brentuximab vedotin and anti‐programmed death‐1 (PD‐1) antibodies, are now being incorporated into frontline therapy.
Management of Relapsed/Refractory Disease
High‐dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD‐1 blockade, non‐myeloablative allogeneic transplant, or participation in a clinical trial should be considered.
Non-Hodgkin lymphomas are lymphoid malignant neoplasms with diverse biological and clinical behavior. Patients typically present with persistent painless lymphadenopathy, but some patients may ...present with constitutional symptoms or with involvement of organs other than the lymphoid and hematopoietic system. An accurate diagnosis, careful staging of the disease, and identification of adverse prognostic factors form the basis of treatment selection. Patients commonly receive chemoimmunotherapy as initial treatment, and radiation therapy may be added if patients have early-stage disease. Most patients respond well to treatment, but relapses are frequent and additional therapies including stem cell transplant are often needed. Because many subtypes of lymphoma remain incurable with current management strategies, clinical trials are in progress to identify novel therapies with promising activity in this disease.
Brentuximab vedotin Ansell, Stephen M.
Blood,
11/2014, Letnik:
124, Številka:
22
Journal Article
Recenzirano
Odprti dostop
Brentuximab vedotin is an anti-CD30 antibody-drug conjugate with proven efficacy in patients with CD30+ malignancies, including classical Hodgkin lymphoma and anaplastic large cell lymphoma. ...Promising activity has also been seen in other lymphomas that express CD30. Because of its acceptable toxicity profile and significant clinical efficacy, single-agent brentuximab vedotin is an approved treatment for relapsed patients with these diseases. Brentuximab vedotin has safely been combined with chemotherapy and is now being compared with standard treatments in randomized trials.
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