Treatment of non-Hodgkin's lymphoma (NHL) with radiolabeled antibodies (mAbs)

Abstract

Most patients with non-Hodgkin's lymphoma (NHL) achieve remission but, despite newer drugs, the natural history of this disease has not improved during the last 20 years. Less than one half of patients with aggressive NHL are cured, and few of those with low-grade NHL are curable. Furthermore, NHL becomes progressively more chemoresistant while remaining responsive to external beam radiation therapy. Radioimmunotherapy (RIT) is a logical strategy for the treatment of NHL because this disease is multifocal and radiosensitive. Because of their remarkable effectiveness for RIT, 2 anti-CD20 monoclonal antibodies (mAbs), one labeled with (111)In for imaging or (90)Y for therapy and a second labeled with (131)I for imaging and therapy, have been approved for use in patients with NHL. These drugs have proven remarkably effective and safe. Evidence for the importance of the radionuclide is manifested by the data in the randomized pivotal phase III trial of (90)Y-ibritumomab that revealed response rates were several times greater in the (90)Y-ibritumomab arm than in the rituximab arm. A second drug for RIT, (131)I-tositumomab, was compared in a pivotal trial with the efficacy of the last chemotherapy received by each patient. Once again, response rates were much higher for RIT. Both (90)Y-ibritumomab and (131)I-tositumomab require preinfusion of several hundred milligrams of unlabeled anti-CD20 mAb to obtain "favorable" biodistribution, that is, targeting of NHL. Response rates for other mAbs and radionuclides in NHL also have been high but these drugs have not reached the approval stage. These drugs can be used safely by physicians who have suitable training and judgment. Unlike chemotherapy, RIT is not associated with mucositis, hair loss, or persistent nausea or vomiting. Although hematologic toxicity is dose limiting, hospitalization for febrile neutropenia is uncommon. Randomized trials of RIT in different formulations have not been conducted, but there is evidence to suggest that the mAb, antigen, radionuclide, chelator, linker, and dosing strategy may make a difference in the outcome.