Copyright 2010 Nephron
Results of a small trial suggest the radiolabeled anti-CD25 antibody 90Y-daclizumab can treat certain patients with relapsed/refractory Hodgkin lymphoma (HL).
90Y-daclizumab produced responses in 50% of patients studied, and most of these were complete responses.
Several patients developed myelodysplastic syndrome (MDS) after receiving 90Y-daclizumab, but researchers found they could prevent this side effect with pretreatment screening.
John Janik, MD, of the National Cancer Institute in Bethesda, Maryland, and his colleagues described this research in PNAS.
The researchers conducted this study to determine if CD25 is a favorable target for systemic radioimmunotherapy in HL. The team noted that although most normal cells don’t express CD25, it is expressed by a minority of Reed–Sternberg cells and by most polyclonal T cells rosetting around Reed–Sternberg cells.
So the researchers tested the anti-CD25 antibody 90Y-daclizumab in 46 patients with relapsed and refractory HL. Patients received 90Y-daclizumab at 10 mCi to 15 mCi every 6 to 10 weeks for up to 7 doses.
The overall response rate was 50%. There were 14 complete responses and 9 partial responses. Fourteen patients had stable disease, and 9 progressed.
The researchers noted that responses occurred in patients whose Reed–Sternberg cells expressed CD25 and in those whose neoplastic cells were CD25-negative, as long as associated rosetting T cells expressed CD25.
Grade 3 or higher toxicities observed in this study included lymphopenia (n=10), neutropenia (n=7), MDS (n=6), thrombocytopenia (n=5), anemia (n=5), and pneumonia (n=2).
At a median follow-up of 9 years, MDS had occurred in 6 patients. They had received a mean of 3.2 doses of 90Y-daclizumab. Prior to 90Y-daclizumab, they had received a mean of 6.2 courses of chemotherapy.
The median time from the initiation of 90Y-daclizumab to MDS diagnosis was 37 months. A retrospective review of 1 patient with MDS revealed that the patient had cytogenetic aberrations on chromosomes 5 and 7 after receiving chemotherapy but before starting 90Y-daclizumab.
So the researchers changed the trial’s entry criteria to require a bone marrow karyotype analysis, and patients who had aberrations were excluded. None of the 16 patients who entered the trial after this change developed MDS.
The researchers said this study is too small to draw meaningful conclusions about the relative roles of chemotherapy and 90Y-daclizumab in the pathogenesis of MDS.
However, this complication is a serious concern, and any subsequent trial should require cytogenetic studies of bone marrow specimens before patients receive systemic radioimmunotherapy.
