Commentary on Abstracts #1296, #1722, and #1721

The results published to date with Bexxar and IDEC-Y2B8 have been very promising. Bexxar is an iodine-131 anti-CD20 conjugate which, in a single-institution study including previously treated patients, achieved a response rate of 79%, including a 50% complete remission rate (Kaminski et al: J Clin Oncol 14:1974-1981, 1996), with complete remissions lasting a median of more than 16.5 months. Among previously treated patients, 71% achieved a complete remission and 39% attained a partial remission, for an overall response rate of 100%. The complete remissions lasted 3 to 17+ months (Kaminski et al : Proc Am Soc Clin Oncol 17:2a [abstract 6], 1998).

Press, Liu, and coworkers have used higher doses of iodine-131-labled anti-CD20, requiring stem support (Lui et al: J Clin Oncol 16:3270-8, 1998), and have reported a 79% rate of complete remissions and an overall response rate of 86%. With a median follow-up of 42 months, the estimated progression-free survival rate was 68% with an overall survival rate of 42%.

Press and coworkers are also exploring the use of high-dose Bexxar to replace total-body irradiation in the setting of bone marrow transplantation. While these studies are encouraging, this approach currently can be performed only at a limited number of centers with sufficient expertise and appropriate facilities.

At the ASH meeting, Kaminski et al (abstract #1296) presented the results of a multicenter trial of this antibody that accrued 60 patients with low-grade or transformed NHL. When compared with the outcome from the patient’s previous chemotherapy regimen, antibody therapy was associated with a higher response rate and more durable responses than the prior treatment. Thus, antibody therapy offers a suitable alternative to additional chemotherapy.

Radioimmunoconjugates are more difficult to administer than unconjugated antibodies. Bexxar, for example, would not be considered feasible for general office practice because of the relatively long half-life of the iodine-131 and regulations concerning its administration. Several states require that this isotope be administered in an inpatient setting, although reversal of this policy is imminent.

IDEC-Y2B8, a true beta-emitter, has a short half-life, and there are currently no obstacles to outpatient administration of this agent. Witzig et al (abstract #1722) presented response data from a phase I/II trial of Y2B8 in 58 relapsed or refractory patients with small lymphocytic, follicular, diffuse mixed or large cell, or mantle cell NHL . The overall response rate was 67%, including a 25% rate of complete remissions.

The authors also evaluated whether this radioimmunoconjugate could be safely and effectively administered to patients with significant splenomegaly, in whom the spleen may act as an antibody “sink,” resulting in limited drug efficacy. Four of their eight patients with baseline splenomegaly responded. This response rate was lower than the 74% rate seen in patients without splenomegaly, but the difference was not significant. Six of the eight patients had complete resolution of splenomegaly.

Therefore, like rituximab, the use of Y2B8 may not be limited to patients without bulky disease.

Unlike the unconjugated monoclonal antibodies, the new radioimmunoconjugates have the potential for myelotoxicity as a consequence of the isotope localizing in bone marrow involved by lymphoma. Wiseman et al (abstract #1721) evaluated the Y90 IDEC-Y2B8 anti-CD20 monoclonal antibody to determine factors that might predict myelosuppression. Surprisingly, the baseline platelet count and degree of bone marrow involvement were better predictors of safety than was dosimetry. Based on this experience, the process of antibody administration can be simplified and the cost reduced by eliminating the need for bone marrow dosimetry prior to administration of this agent.

Nevertheless, this study included patients with < 25% bone marrow involved by tumor, and other measures may be needed to protect patients with more extensive bone marrow involvement. A phase I trial of Bexxar is being planned to identify a dose of the agent that can be safely administered to patients with more extensive bone marrow involvement.