Lymphomas are the fifth most common
malignancy in the United States and are increasing in incidence. Despite being among the most responsive
malignancies to radiation and
chemotherapy, the majority of patients relapse or have progressive disease.
Monoclonal antibodies (MAbs) directed at cell-specific
surface antigens have been useful in the diagnosis of
lymphomas and, more recently, the therapeutic mouse-human chimeric MAb
rituximab has demonstrated effectiveness in
B cell lymphomas. Conjugating MAbs to
radionuclides is a strategy for improving the efficacy of MAb
lymphoma therapy by delivering radiation in close proximity to the tumour (
radioimmunotherapy or RIT). In addition, the low dose rate of the delivered radiation may exert a greater antitumour activity than an equivalent dose of conventional external beam radiation. The antigenic targets for MAb
therapy have included CD20, CD22,
HLA-DR, and B cell idiotype.
Radionuclides that have been used include
iodine-131,
yttrium-90, and
copper-67; there are relative merits and disadvantages to each source of radiation. Clinical studies to date have focused on relapsed and refractory patients with both indolent and aggressive
lymphomas, although more recent studies have included previously untreated patients with indolent
lymphoma.
Radioimmunoconjugate has been delivered as either single or multiple doses. Response rates have varied widely, dependent on the patient population and the response criteria. Of note, complete responses can be achieved in this typically refractory patient group. Toxicities have generally consisted of mild infusion-related
nausea,
fever,
chills, and
asthenia.
Neutropenia and
thrombocytopenia are the dose-limiting toxicities and have prompted the incorporation of autologous stem cell support as a means of achieving dose escalation. To date, RIT has been delivered to highly selected patients in relatively few centres with requisite equipment and specialised personnel. In addition to these requirements, cost is likely to be a barrier to widespread use. The combination of RIT with
chemotherapy at conventional or high dose, or with
biological agents is a fertile area for investigation. The potential of RIT in the treatment for
lymphomas will be defined only by well designed comparative prospective clinical studies.