Novel Mechanisms of Resistance in CLL: Variant BTK Mutations in Second-Generation and Noncovalent BTK Inhibitors.

BTK inhibitors (BTKi) are an established standard of care in CLL. The covalent BTKi ibrutinib, acalabrutinib and zanubrutinib bind to BTK C481 and are all susceptible to the C481S mutation. Non-covalent BTKi including pirtobrutinib overcome C481S resistance but are associated with multiple variant (non-C481) BTK mutations, including those associated with resistance to acalabrutinib and zanubrutinib (T474 codon and L528W mutations).

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.

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.

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).