Apart from factors such as genetic events that contribute to the malignant transformation in Waldenström’s macroglobulinemia (WM), the bone marrow microenvironment has been identified as a crucial player in WM disease progression. Similarly, it appears to be essential for the emergence and progression of multiple myeloma (MM) and constitutes a significant reason why MM patients are not amenable to cure but inevitably develop relapses.
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.
I would like to address two factors here. The first one relates to favorable disease biology. Patients who have mutated immunoglobulin genes or lack TP53 mutations or 17p loss are more likely to experience treatment-free remission. The other main factor is treatment capable of inducing deep remission, which is usually combination therapy. Historically, the fludarabine/cyclophosphamide/rituximab regimen was the gold standard with which patients could achieve deep remissions.
High relapse rates after standard-of-care regimens in the frontline setting are typical of mantle cell lymphoma (MCL), which is an aggressive, rare, B-cell Non-Hodgkin lymphoma. The second-generation, highly selective BTK inhibitor acalabrutinib has been approved in the US for the treatment of patients with MCL after ≥ 1 prior therapy based on the single-arm, open-label, multicenter, phase II ACE-LY-004 study.
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.
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.
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.
Constitutive activation of the Bruton’s tyrosine kinase (BTK) pathway has been shown to induce malignant cell survival in patients with Waldenström’s macroglobulinemia (WM). The disease is based on the accumulation of IgM-secreting clonal lymphoplasmacytic cells in the bone marrow and extramedullary sites. MYD88L265P mutations (> 90 % of cases) and CXCR4WHIM-like mutations (approximately 27 % of cases) have been established as the pathologic hallmarks of WM.
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.
