Diffuse large B‐cell lymphoma

Abstract

Large B‐cell lymphoma, the prototype of aggressive non‐Hodgkin lymphomas, is both the most common lymphoma and accounts for the highest global burden of lymphoma‐related deaths. For nearly 4 decades, the goal of treatment has been “cure”, first based on CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), and subsequently with rituximab plus CHOP. However, there is significant clinical, pathologic, and biologic heterogeneity, and not all patients are cured. Understanding and incorporating this biologic heterogeneity into treatment decisions unfortunately is not yet standard of care. Despite this gap, we now have significant advances in frontline, relapsed, and refractory settings. The POLARIX trial shows, for the first time, improved progression‐free survival in a prospective randomized phase 3 setting. In the relapsed and refractory settings, there are now many approved agents/regimens, and several bispecific antibodies poised to join the arsenal of options. While chimeric antigen receptor T‐cell therapy is discussed in detail elsewhere, it has quickly become an excellent option in the second‐line setting and beyond. Unfortunately, special populations such as older adults continue to have poor outcomes and be underrepresented in trials, although a new generation of trials aim to address this disparity. This brief review will highlight the key issues and advances that offer improved outcomes to an increasing portion of patients.

PI3Kδ activation, IL6 over-expression, and CD37 loss cause resistance to the targeting of CD37-positive lymphomas with the antibody-drug conjugate naratuximab emtansine

“…More than half of DLBCL patients can achieve remission, but around 40% of them experience refractory disease or relapse following an initial positive response (3). Regrettably, the prognosis for many of these cases remains unsatisfactory despite introducing the most recent antibody-based or cellular therapies (3,4), underscoring the importance of innovating new therapeutic strategies and gaining insights into the mechanisms of therapy resistance. CD37 is a transmembrane glycoprotein belonging to the tetraspanin family, primarily expressed on the surface of immune cells, principally in mature B cells but also, at lower levels, in T cells, macrophages/monocytes, granulocytes and dendritic cells (5) (6)(7)(8).…”

Systemic Capillary Leak Syndrome as a Paraneoplastic Syndrome

“…Otherwise, it can result in death within a few weeks. Although most patients present in an advanced stage of the disease, more than 60% can be cured with R-CHOP immunochemotherapy, which shows the importance of the diagnosis [9].…”

Bispecific antibodies in indolent B-cell lymphomas

“…monoclonal antibody molecules coupled with a drug/toxin payload, have made their mark in lymphomas, e.g. Brentuximab vedotin in Hodgkin Lymphoma, Polatuzumab vedotin and Loncastuximab teserine in diffuse large B-cell Lymphomas ( 4 , 5 ). Chimeric antigen receptor- T (CAR-T) cell therapy uses T-cells, re-engineered to express a designer T-cell receptor (TCR) against a lymphoma directed antigen like CD19 to clinical benefit from tumour cell lysis independent of major histocompatibility (MHC) restricted T-cell receptor activation of T-cells ( 6 ).…”