Researchers from the Fred Hutchinson Cancer have reported that high-dose radioimmunotherapy may be superior to conventional high-dose therapy with autologous stem cell support for relapsed follicular non-Hodgkin's lymphoma (NHL). The results of these analyses were reported in the October 2003 issue of Blood.

High-dose chemotherapy or chemo-radiotherapy is often used to treat patients with follicular NHL who have failed conventional therapies. Anti-CD 20 antibodies have been used alone or linked to isotopes for the treatment of patients with CD 20 positive NHL. Currently, there are four antibody products approved by the U.S. Food and Drug Administration (FDA) for malignancies of B cell lymphocytes. Rituxan®, an anti-CD20 antibody, has been approved for the treatment of patients with NHL who have failed initial therapy. Campath®, an anti-CD52 antibody, has been approved for the treatment of patients with chronic lymphocytic leukemia (CLL) who have failed initial treatment. Zevalin™, which is essentially Rituxan® linked to 90Yttrium, is approved for treatment of patients with NHL who have failed initial chemotherapy. Recently the FDA also approved tositumomab (Bexxar®), which is an anti-B cell antibody linked to iodine 131. The FDA approval of Bexxar® is for non-marrow ablative doses.

In the current clinical trial, Bexxar® was administered in individualized marrow ablative doses to 125 patients with failed follicular NHL. The average dose of irradiation achieved in critical organs was reported to be approximately 27 Gy. Patients were excluded who did not obtain a favorable distribution of the antibody on pre-treatment testing. The investigators compared the outcomes of patients receiving Bexxar® to a concurrent group of 98 patients receiving conventional transplants with high-dose chemo-radiotherapy (70%) or high-dose chemotherapy without total body irradiation (30%). Overall 5-year survival of the Bexxar® group was reported to be 67% compared to 53% for the conventional group. They also reported that the 5 year progression-free survival was 48% for the Bexxar® group compared to 29% for the conventional group. Treatment-related mortality of Bexxar® patients was reported to be less than half that observed with conventional autologous transplants.

Comments: These are very promising results and the authors stated that the Bexxar® group had a worse prognosis than the conventionally treated group as measured by the international prognostic index and LDH. However, the Bexxar® patients were selected for localization of the antibody and absence of splenomegaly. This comparison could be meaningful but it cannot be proven without a randomized trial. There must be clear advantages to Bexxar® before this approach is adopted as routine due to the increased costs of Bexxar® compared to conventional drugs and general labor intensity of this form of treatment.

Gopal AK, Gooley TA, Maloney DG, et al. High-dose radioimmunotherapy versus conventional high-dsoe therapy and autologous hematopoietic stem cll transplantation for relapsed follicular non-Hodgkin lymphoma: a multivariable cohort analysis. Blood 2003;102:2351-2357.