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BioOncology Watch Timely Information for Practicing
Physicians |
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FEBRUARY 2000 Non-Hodgkin’s Lymphoma
(NHL) Radioimmunotherapy (RIT) with IDEC-Y2B8. IDEC-Y2B8 (IDEC Pharmaceuticals
Corp.) consists of a murine anti-CD20
monoclonal antibody, ibritumomab, covalently bound to tiuxetan to which the
radioisotope yttrium-90 is chelated.
Thomas Witzig and colleagues conducted a multicenter phase I/II study
(n=51) of unlabeled rituximab followed by IDEC-Y2B8 treatment in
relapsed/refractory NHL patients.
Rituximab was given prior to RIT to clear peripheral blood
B-lymphocytes to optimize biodistribution of the radiolabeled antibody. pre-RIT dosing with rituximab at 250 mg/m2
was well-tolerated and the maximum-tolerated single dose of IDEC-Y2B8 that
can be administered in the outpatient setting without stem-cell support is
0.4 mCi/kg. The principal side effect
was reversible hematologic toxicity and only one patient developed an anti-antibody
response (human antichimeric antibody/human antimouse antibody). This trial shows that RIT can be
administered safely and effectively in the outpatient setting. (Witzig TE, et al. J Clin Oncol 1999; 17: 3793-3803) Acute Graft-Versus-Host Disease
(GVHD) Treatment with daclizumab. Daclizumab (Hoffman-LaRoche, Inc.) is a
humanized monoclonal antibody directed against the a chain of
the interleukin-2 receptor (IL-2R).
The interaction of IL-2 and IL-2R enhances lymphocyte proliferation
and differentiation; previous studies have shown the blockade of IL-2R to
abrogate acute GVHD. D. Przepiorka
and coworkers treated patients with advanced or steroid-refractory GVHD with
daclizumab 1mg/kg on either days 1,8,15,22,29 (n=24) or days 1,4,8,15,22 (n=19). The CR rate (achievement of stage 0 GVHD)
on day 43 was 29% and 47% for the first and second groups, respectively. Day 120 survival was 29% and 53%,
respectively. There were no
infusion-related reactions and no serious side effects reported. Daclizumab is an active agent for the
treatment of acute GVHD and the second regimen has been recommended for
further studies. (Przepiorka D, et
al. Blood 2000; 95: 83-89) Chronic Myelogenous
Leukemia (CML) Molecular heterogeneity in cytogenetic responders. Andreas Hochhaus et al. utilized a reverse
transcriptase polymerase chain reaction (RT-PCR) assay to quantify levels of
BCR-ABL transcripts in peripheral blood from 54 CML patients with a complete
cytogenetic response to interferon-a therapy. All 54
patients had molecular evidence of residual BCR-ABL transcripts and the
results were expressed as a BCR-ABL/ABL ratio. The median BCR-ABL/ABL ratio at maximal response of 14 patients
who were observed to relapse was greater than in those who remained in complete
cytogenetic remission (0.49% vs. 0.021%, P<0.0001). These findings show that molecular
evidence of disease is rarely if ever eliminated and that the level of
molecular minimal residual disease correlates with the risk for relapse. The authors suggested that interferon-a be
continued at least until low levels of residual disease are achieved in CML
patients who have a complete cytogenetic response. (Hochhaus A, et al. Blood
2000; 95: 62-66) Donor lymphoctye infusion (DLI) administration and
GVHD. F Dazzi and
colleagues compared the results and GVHD incidence for CML patients relapsing
after allogeneic stem cell transplantation who were treated with DLI
administered as a single bulk dose regimen (BDR) (n=28) versus a multiple
escalating dose regimen (EDR) (n=20).
The median interval between EDR doses was 20 weeks (range, 12-33
weeks). The complete cytogenetic
remission rate was similar for the BDR group compared to the EDR group (67%
vs. 91%, P=0.70). However, the
incidence of GVHD was higher in the BDR patients than in the EDR patients
(44% vs. 10%, P<0.011). In
addition, an analysis of BDR and EDR patients who received comparable total
lymphocyte doses confirmed the reduced GVH risk in the EDR group. These results indicate that DLI
administered as an EDR decreases the risk for GVHD and maintains
effectiveness in the treatment of CML patients in relapse. (Dazzi F, et al. Blood 2000; 95: 67-71) Effects of interferon-a (IFN) therapy on allogeneic bone marrow
transplantation (BMT) outcomes. IFN is increasingly used as initial therapy for CML. Two recent studies have assessed the
effect of prior IFN treatment on the outcome of allogeneic BMT in CML
patients. Rudiger Hehlmann and
colleagues in the German CML Study Group reviewed data from 197 CML patients
who underwent BMT. Outcomes after BMT
were similar for patients who received pretreatment IFN compared to those who
received pretreatment chemotherapy.
Survival was not affected by duration of IFN therapy, however, 5-year
survival was found to be 46% for 50 patients who received IFN within that
last 90 days before BMT and 71% for 36 patients who did not (P=0.0057). No differences in causes of death were
found between these two patient groups.
In a second study, Sergio Geralt et al. reviewed data from the
International Bone Marrow Transplant Registry and observed no differences in
survival or leukemia-free survival for CML patients who received a short
course (median of 2 months) of IFN before BMT (n=209) compared to those who
received hydroxyurea before BMT (n=664).
No data on IFN use within 90 days of BMT was reviewed in this
study. These studies indicate that
clinical outcomes after BMT are not compromised by prior IFN therapy.
However, the finding by Hehlmann et al. that patients receiving IFN within 90
days of BMT may have a poorer 5-year survival suggests the need for further
investigation to determine optimal timing of IFN therapy. (Hehlmann R, et al. Blood 1999; 94: 3668-3677 and
Giralt S, et al. Blood 2000; 95: 410-415) |
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