Marginal Zone Lymphoma: Treatment Update With a Focus on Systemic Approaches

ABSTRACT Marginal zone lymphoma (MZL) is the second most common indolent B‐cell lymphoma and comprised of three clinical subtypes based on site of involvement: extranodal marginal zone lymphoma (usually of mucosa‐associated lymphoid tissue), nodal marginal zone lymphoma, and splenic marginal zone lymphoma (often with circulating villous lymphocytes). MZL is the prototype for an antigen‐driven malignancy, and there are clear areas where elimination of the antigenic trigger leads to lymphoma regression. Although there is an excellent prognosis, the disease remains incurable, and the majority of patients will need repeated therapy for disease control over the course of their lifetime. Current treatment paradigms include rituximab monotherapy and chemoimmunotherapy in the frontline setting. In the relapsed or refractory setting, there are exciting advances including the recent approval of the covalent BTK inhibitor, zanubrutinib. Emerging therapies include CAR‐T cell and T‐cell engaging bispecific antibodies, with promising early results. This primer on MZL will discuss the three subtypes and focus on treatment approaches in the treatment‐naïve and relapsed/refractory setting.