T-Cell Engaging Antibodies in Diffuse Large B Cell Lymphoma-An Update.

Novel cellular immunotherapies such as T-cell engaging antibodies (TCEAbs) are changing the landscape of treatment for diffuse large B cell lymphoma (DLBCL), especially in the relapsed/refractory (R/R) setting. TCEAbs harness the power of the host immune system to induce killing of tumor cells by binding to both the tumor antigen and the T-cell receptor. Since the approval of blinatumomab for R/R acute lymphoblastic leukemia, there has been significant development in novel TCEAbs. Many of these novel TCEAbs have shown promising effectiveness in R/R DLBCL, with favorable response rates including complete remissions, even in heavily pretreated patients. There are unique therapy-related toxicities with TCEAbs, namely cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS), and it is important to both recognize and manage these side effects appropriately. This review examines the development and mechanism of action of these TCEAbs, and the available published data from clinical trials. Their role in the treatment of DLBCL, the management of therapy-related adverse events, and the mechanisms of resistance will also be discussed.

Non-anaemic iron deficiency.

Iron deficiency without anaemia is common. Patients may present with unexplained, non-specific symptoms. Iron studies will usually show a low ferritin and low transferrin saturation with a normal haemoglobin concentration. The cause of the iron deficiency should be identified and managed. There is limited evidence about the benefits of giving iron to people who do not have anaemia. If there is iron deficiency, most people can be given oral iron supplements. Iron studies are repeated after 60-90 days of oral iron supplements. Further investigations are needed if the iron deficiency has not been corrected. Some patients, including those who have not responsed to oral supplements may benefit from intravenous iron. There is no role for intramuscular injections of iron.

Humoral immune failure defined by immunoglobulin class and immunoglobulin G subclass deficiency is associated with shorter treatment-free and overall survival in Chronic Lymphocytic Leukaemia.

Immune dysfunction attributed to hypogammaglobulinaemia is common in chronic lymphocytic leukaemia (CLL) and infection is a major contributor to morbidity and mortality. A higher incidence of multiple immunoglobulin and immunoglobulin G (IgG) subclass deficiency was associated with more advanced disease (P < 0·001 and P < 0·001, respectively) in a cohort of 147 CLL patients. Multiple immunoglobulin and IgG subclass deficiency were significantly associated with shorter treatment-free survival (TFS) (P < 0·001 and P = 0·006, respectively). The association between disease stage and immune dysfunction demonstrated by these data suggest aspects of immune deficiency correlate with disease severity and may be associated with shorter TFS in CLL.