Non-Myeloablative Radio-Immunotherapy With a Iodine-131-Tagged Anti-CD30 Antibody (131I-Ki-4) in Patients With Refractory Hodgkin's Lymphoma

Reviewer: Walter Sall, MD
OncoLink
Last Modified: December 10, 2002

Presenter: Roland Schnell
Presenter's Affiliation: University of Cologne
Type of Session: Scientific

Background

Relapsed Hodgkin's Disease (HD) has a poor prognosis. More treatment alternatives are neeeded.
HD is a good target for immunotherapy given high expression of surface antigens including CD25 and CD30. HD also tends to be well vascularized and sensitive to therapeutic radiation.
For these reasons, a radiolabelled monoclonal antibody (Mab) was developed as a potential new therapy for HD.
Prior HD Mab therapy has shown only moderate efficacy. It was hoped that the addition of a radiolabel would boost the efficacy.
In this study, a murine anti-CD30 Ki-4 Mab tagged with I-131 was used. CD30 is a 120kD transmembrane cytokine receptor highly expressed on Reed-Sternberg cells that can be shed into the serum.

Materials and Methods

This was a preliminary trial to determine dosimetry and pharmacokinetics.
heavily pretreated HD patients were enrolled.
Patients were first given a 5mg dose of unlabelled Ki-4 to saturate soluble CD30. A dosimetric dose of 5mCi was then given after which sequential whole body counts were taken over six days.
On day 8, the therapeutic dose was given, calculated to deliver a total body radiation dose of 0.125, 0.25 or 0.35Gy.
Patients were then monitored with nuclear scans, total body dosimetry and conventional measures of disease progression (CT scan).

Results

21 refractory patients were enrolled, 19 post-transplant. Median age was 30.
Imaging of I-131 Ki-4 demonstrated enhancement of involved areas in 5 of 21 patients. Only lesions larger than 5cm showed enhancement.
One patient obtained a CR, 5 a PR and 3 sustained a mixed response. Median response duration was 2-3 months.
Grade IV hematologic toxicity occurred in 7 of 21 and was primarily thrombocytopenia. In 5 patients, thrombocytopenia persisted until time of death.
Several patients had mild nausea and fatigue.

Author's Conclusions

The 30% response rate and 25% positive imaging rate demonstrate that this new treatment modality is feasible and warrants further investigation.
It must be determined which patients are most likely to benefit from this therapy. Increased specificity in order to decrease the rates of thrombocytopenia is also needed.

Clinical/Scientific Implications

In Non-Hodgkin's Lymphoma, Mab therapy (Rituximab, Zevalin) is palying an increasing role in de novo and relapsed disease. The authors of this study are applying the same strategy to HD treatment. This very preliminary paper serves as proof of priciple. It appears that they have succesfully created a radiolabelled Mab with specific activity against HD. Further study is needed in order to increase the efficacy of this technique and reduce the hematologic toxicity. This preliminary data provides hope that novel therapies for those that fail conventional HD therapy are on the horizon.

Oncolink's ASH Coverage made possible by an unrestricted Educational Grant from Ortho Biotech.