NEW ORLEANSThe radioactive monoclonal antibody ibritumomab
tiuxetan (Zevalin, IDEC-Y2B8) may be a useful therapy in patients
with rituximab-refractory follicular non-Hodgkins lymphoma
(NHL). In addition, Y2B8 can be used safely in patients with mild
thrombocytopenia, researchers reported at the ASH meeting.
Y2B8 is an anti-CD20 murine monclonal antibody conjugated to
tiuxetan, which forms a strong chelate with the pure beta emitting
isotope yttrium 90. Y2B8 destroys cancer cells presumably by direct
induction of apoptosis and by the effects of the radiation from
Open Label Study
Leo I. Gordon, MD, of Northwestern University in Chicago reported
interim results of an open-label, nonrandomized, controlled,
multicenter trial of Y2B8 at a dose of 0.4 mCi/kg in patients with
follicular NHL refractory to rituximab (Rituxan). These patients
either did not respond to rituximab or responded but suffered disease
progression in 6 months or less.
Median number of prior therapies was 4 (range 1 to 9). Patients had
absolute neutrophil count (ANC) greater than 1,500 cells/mm³ at
entry and platelet counts greater than 150,000 cells/mm³.
Exclusion criteria included prior bone marrow or stem cell
transplant, prior radioimmunotherapy, central nervous system
lymphoma, chronic lymphoblastic leukemia or AIDS lymphoma, pleural or
peritoneal invasion, elevated total bilirubin or creatinine, prior
external beam irradiation to more than 25% of active bone marrow, or
presence of human antimurine or antichimeric antibodies.
At study entry, 38% of patients had bone marrow involvement, 10% had
splenomegaly, 80% had bulky disease larger than 5 cm (including 56%
with disease larger than 7 cm), and 76% were resistant to chemotherapy.
Safe and Effective
Adverse events [at this interim analysis of the first 29
patients treated] were primarily hematologic, transient, and
reversible, Dr. Gordon reported. The ANC median nadir was
800 cells/mm³. Patients with Grade 3 and 4 nadirs recovered in a
median of 9 days. The median platelet nadir was 34,000 cells/mm³.
Patients with Grade 3 and 4 nadirs recovered in a median of 14 days.
Median hemoglobin nadir was 10.5 g/dL. Grade 4 thrombocytopenia
occurred in 14% of patients, and Grade 4 neutropenia occurred in 28%
Two patients with infection were hospitalized, and both recovered. No
patients developed human antimouse antibodies (HAMA) or antichimeric
Overall response rate was 46% in the 28 patients evaluable for
response. All were partial responses, with median tumor measurement
reduction (sum of the products of the perpendicular diameters) of 80%
This interim analysis suggests that Zevalin radioimmunotherapy
is safe and effective in patients with rituximab-refractory
follicular NHL, Dr. Gordon concluded.
Reduced doses of Y2B8 (5.0 mCi of indium 111 Zevalin, 0.3 mCi/kg of
yttrium 90 Zevalin) can be used safely and effectively in patients
with mild thrombocytopenia, according to Thomas Witzig, MD, of the
Mayo Clinic in Rochester. A common problem in patients with relapsed
or refractory B-cell NHL, pre-existing thrombocytopenia often limits
future therapeutic options.
Zevalin dosing based on weight and baseline platelet count can
be used for NHL patients with no history of autologous bone marrow
transplant (ABMT) and less than 25% bone marrow involvement,
obviating the need for dosimetry, Dr. Witzig noted. He reported
on an open-label, single-arm, phase II study of 26 patients with
relapsed or refractory low-grade, follicular, or transformed NHL. All
patients had mild thrombocytopenia (100,000-149,000 cells/mm³)
and ANC greater than 1,500/mm³. None had been previously treated
Patients were treated initially with rituximab and indium 111 Y2B8
for imaging studies, then with rituximab and yttrium 90 Y2B8
infusions. Interim analysis in 24 patients showed an overall response
rate of 67%, which included a 21% complete response (CR) rate and a
46% partial response (PR) rate.
Toxicity was primarily hematologic, transient, and
reversible, Dr. Witzig said. Median nadirs for patients
receiving 0.3 mCi/kg were ANC of 600/mm³, platelets of
34,000/mm³ and hemoglobin of 10.0 g/dL. Grade 4 hematologic
patients included neutropenia (31%), thrombocytopenia (12%), and
Dr. Witzig pointed out that dosimetry did not predict hematologic
toxicity. Relapsed or refractory, low-grade, follicular or
transformed CD20+ B-cell NHL patients with mild thrombocytopenia can
be safely treated with reduced-dose (0.3 mCi/kg) Zevalin with
excellent clinical response, Dr. Witzig concluded.