Preface – ASH 2020

Heinz Ludwig, MD, Director of the Wilhelminen Cancer Research Institute, Department of Medicine I, Center for Oncology, Hematology and Palliative Care, Wilhelminen Hospital, Vienna, Austria
Dear Colleagues,
The ASH Annual Meeting and Exposition is the premier event for presentation of novel data on malignant and non-malignant hematologic diseases, attracting up to 30,000 specialists from all over the world. The 62nd ASH Annual Meeting was planned to be held on December 5–8, 2020 in San Diego, California, but due to the COVID-19 pandemic had been transformed to an all-virtual event. Attendees had access to thousands of scientific abstracts highlighting cutting-edge research in hematology. This publication summarizes work presented in the field of B-cell malignancies with a focus on targeted therapies.
Inhibition of the Bruton’s tyrosine kinase (BTK) has been implemented as a mainstay of treatment in various types of hematologic malignancies, including Waldenström’s macroglobulinemia, chronic lymphocytic leukemia, marginal zone lymphoma, and mantle cell lymphoma. Later-generation BTK inhibitors designed to achieve optimized selectivity offer advantages with respect to tolerability and efficacy compared to first-generation BTK inhibition. Benefits have been observed with these agents irrespective of factors such as pretreatment or cytogenetic risk.
Progress is also ongoing regarding other drug classes such as PI3Kδ inhibitors and anti-CD20 antibodies that complement the armamentarium available for the treatment of various B-cell malignancies. Immune checkpoint inhibition might also play a role in the future, although a variety of inhibitory receptors apart from PD-1 and PD-L1 are still awaiting investigation in terms of their clinical usefulness as targets for drug therapy.
Naturally, combinations are a major area of research given the importance of achieving deep remission that allows for long-lasting disease-free survival. The wide range of drugs already established in the field of hematologic diseases enables the assessment of new regimens that might represent a major step forward in terms of patient life expectancy and quality of life.
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Mediastinal gray zone lymphoma (MGZL) is an extremely rare type of Non-Hodgkin lymphoma with a predominance in young men. This disease exhibits transitional features between nodular sclerosis classical Hodgkin lymphoma (cHL) and primary mediastinal B-cell lymphoma (PMBL). However, compared to PMBL, survival of patients with MGZL is inferior after conventional chemotherapy.
Finding the way among a multitude of targets and regimens
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Advancing treatment in patients with mantle cell lymphoma
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Approaching marginal zone lymphoma from various angles
Approximately 10 % of Non-Hodgkin lymphomas are classified as marginal zone lymphoma (MZL) [1]. This is a heterogeneous malignancy with three main subtypes (i.e., extranodal, nodal, splenic) arising from memory B cells in the marginal zone of secondary lymphoid follicles [2, 3]. Due to its rarity and heterogeneous nature, the optimal therapeutic strategies for patients with MZL have been difficult to define.
Insights from early clinical trials on targeted treatment in B-cell malignancies
Richter’s transformation (RT), which describes transformation of CLL/SLL to diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma, is a rare event occurring in approximately 5–7 % of CLL cases [1]. However, defined standards of care are lacking, and outcomes are generally poor once patients are refractory to rituximab plus chemotherapy.
Management of CLL patients: BTK inhibition and beyond
BTK inhibitors, the Bcl-2 inhibitor venetoclax and anti-CD20 antibodies such as obinutuzumab have dramatically changed the therapeutic landscape of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Ibrutinib, as the first-generation representative of the BTK inhibitor class, is a therapeutic mainstay, although it has notable shortcomings that led to the introduction of second-generation agents.