Leo I. Gordon, MD

Management strategies for patients with mantle cell lymphoma continue to demonstrate pendulum-like swings between those appropriate for low-grade lymphoma, and those appropriate for very aggressive lymphoma.

It is clear that as our understanding of both aggressive and indolent lymphomas improves, the goals of treatment change and the bar for success is set higher.

Incorporation of PD-1 blockade into the treatment algorithms for hematologic malignancies is currently being pursued in multiple active clinical trials. Here we review the data on anti–PD-1 monoclonal antibodies to date and discuss ongoing and future clinical trials.

This management guide covers the risk factors, screening, diagnosis, staging, and treatment of non-Hodgkin lymphoma.

The incidence rates of non-Hodgkin lymphoma (NHL) in the United States have almost doubled between 1970 and 1990, representing one of the largest increases of any cancer. Although the overall incidence rates of NHL began to stabilize in the late 1990s, the temporal trends varied by histologic subtype. Some of this increase may be artifactual, resulting from improved diagnostic techniques and access to medical care, or directly related to the development of NHL in 25- to 54-year-old men with human immunodeficiency virus (HIV) infection. However, additional factors must be responsible for this unexpected increase in frequency of NHL that has been observed throughout the United States.

Between 1950 and 1999, the incidence of non-Hodgkin's lymphoma (NHL)rose by 90% in the United States, representing one of the largest increases ofany cancer. Some of this increase may be artifactual, resulting from improveddiagnostic techniques and access to medical care, or directly related to thedevelopment of NHL in 25- to 54-year-old men with human immunodeficiencyvirus (HIV) infection. However, additional factors must be responsiblefor this unexpected increase in frequency of NHL that has been observedthroughout the United States.

Yttrium-90 (Y-90) ibritumomabtiuxetan (Zevalin) radioimmunotherapywas approvedby the US Food and DrugAdministration (FDA) in February2002 and tositumomab/iodine-131(I-131) tositumomab (Bexxar) was approvedby the FDA in June 2003 forthe treatment of patients with relapsedor refractory low-grade, follicular, orCD20-positive transformed B-cellnon-Hodgkin’s lymphoma (NHL),and rituximab (Rituxan)-refractoryfollicular NHL. In this excellentreview, Drs. Ghobrial and Witzigdescribe the rationale for radioimmunotherapyand the relevant clinicaltrials that formed the basis forFDA approval.

Ibritumomab tiuxetan (Zevalin) consists of an anti-CD20 murine IgG1 kappa monoclonal antibody covalently bound to tiuxetan (MX-DTPA), which stably chelates yttrium-90 for therapy. Ibritumomab tiuxetan therapy involves pretreatment with

Ibritumomab tiuxetan (Zevalin) is a murine anti-CD20 monoclonal antibody covalently bound to the chelator tiuxetan, which can securely chelate yttrium-90. We performed a randomized controlled trial