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BioOncology Watch Timely Information for Practicing
Physicians |
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september 2002 RITUXIMAB-REFRACTORY FOLLICULAR
NON-HODGKIN'S LYMPHOMA (NHL) Radioimmunotherapy with
ibritumomab tiuxetan (Zevalin; IDEC Pharmaceuticals). Thomas
Witzig and coworkers administered radiolabeled ibritumomab tiuxetan on an
outpatient basis to 54 patients with follicular NHL refractory to rituximab
(patients with no objective response to rituximab 375 mg/m2 weekly
for 4 weeks or patients that had relapsed within 6 months after rituximab
treatment). Patients received
rituximab 250 mg/m2 intravenously (IV) on Days 1 and 8 to delete
peripheral blood B cells followed by yttrium-90 ibritumomab tiuxetan 0.4
mCi/kg IV on Day 8. The response rate
was 74% (15% complete response rate).
The Kaplan-Meier-estimated time to progression was 6.8 months (range,
1.1 to ³ 25.9
months) for all patients and 8.7 months for responders. The most common adverse events were
hematologic and the incidence of grade 4 neutropenia correlated with
increasing bone marrow involvement with NHL (p = 0.004). The percentage of patients that had grade
4 neutropenia, thrombocytopenia, or anemia was 35%, 9%, and 4%, respectively.
This study shows that ibritumomab tiuxetan treatment can achieve high
response rates in patients with follicular NHL refractory to rituximab, but
the duration of response is generally short-lived. (Witzig TE, et al. Blood 2002;100:3262-3269) CHRONIC LYMPHOCYTIC LEUKEMIA
(CLL) First-line treatment with
Campath-1H. Jeanette Lundin
and associates conducted a multicenter phase II study in which 41 patients with
previously untreated B-CLL were given the humanized anti-CD52 monoclonal
antibody, Campath-1H subcutaneously 3 x weekly for up to 18 weeks. Twenty-five patients (61%) completed all
18 weeks of treatment. Thirty-eight
patients were evaluable and the overall response rate was 87% (95% CI, 76% to
98%; 19% complete remissions). CLL cells were cleared from blood in 95% of
patients (in a median of 21 days).
The median time to treatment failure has not been reached (range, 8 to
44+ months). The incidence of grade 4
neutropenia was 21% and 10% of patients developed CMV reactivation (all
patients rapidly responded to IV ganciclovir). Transient injection site skin
reactions occurred in 90% of patients, however, first-dose reactions commonly
experienced following intravenous Campath-1H were rare or absent. Thus,
subcutaneous Campath-1H resulted in few first-dose adverse
events and may reduce health care costs compared to intravenous
administration. (Lunden J, et al. Blood 2002;100:768-773) Clinical significance of tumor
necrosis factor-a (TNF-a) plasma
level. Alessandra
Ferrajoli and colleagues determined TNF-a levels in peripheral blood samples obtained from 150
consecutive CLL patients. The mean
TNF-a plasma
concentration was higher in CLL patients than in 20 healthy normal volunteers
(16.4 vs. 8.7 pg/mL; p <0.0001).
In addition, higher TNF-a levels in CLL patients were associated with more advanced
stage of disease, chromosomal abnormalities, higher serum beta-2
microglobulin levels, a higher percentage of cells expressing CD38, low
hemoglobin levels, and thrombocytopenia.
Patients having a TNF-a plasma
level >14 pg/mL had shorter survival times (p = 0.00001) and a Cox
multivariate analysis identified the plasma TNF-a level
to be an independent predictor of survival (p = 0.005). These data indicate that the TNF-a plasma
level is a prognostic factor for patients with CLL and that TNF-a may be
a useful therapeutic target.
(Ferrajoli A, et al. Blood 2002;100:1215-1219) MYELOID LEUKEMIA
Targeted a
particle radioimmunotherapy. Joseph Jurcic et al. conducted a phase I study of HuM195, a
humanized anti-CD33 monoclonal antibody, labeled with 213Bi in
patients with advanced myeloid leukemia. The a-emitters can selectively kill
cancer cells with a single atomic decay and may avoid the prolonged
myelosuppression associated with standard b particle-emitting isotope therapy. Eighteen patients were treated with 10.36
to 37.0 MBq/kg 213Bi-HuM195 and no significant extramedullary
toxicity was seen. Myelosuppression
occurred in all 17 evaluable patients with a median time to recovery of 22
days. The absorbed dose ratios
between leukemic sites and whole body were 1000-fold greater than those seen
with b-emitters. A reduction in the percentage of bone
marrow blasts was achieved in 14 (78%) of 18 patients. This study demonstrated that targeted a
particle immunotherapy in humans is feasible. (Jurcic JG, et al. Blood 2002;100:1233-1239) MULTIPLE MYELOMA (MM) Thalidomide and doxorubicin and deep venous thrombosis (DVT). Thalidomide has minimal prothrombogenic activity when used as single-agent therapy. However, the combination of thalidomide with chemotherapy has been reported to be associated with an increased risk of DVT. Maurizio Zangari and colleagues retrospectively analyzed the incidence of DVT in 232 MM patients treated in two protocols investigating the combination of thalidomide treatments with chemotherapy. The patients in these protocols were balanced for known risk factors for DVT. They found that patients receiving thalidomide plus DT-PACE (a doxorubicin-containing regimen consisting of dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide) had a greater incidence of DVT than those treated with thalidomide plus DCEP-T (a non-doxorubicin-containing regimen consisting of dexamethasone, cyclophosphamide, etoposide, cisplatin, and thalidomide) (31of 192 patients [16%] vs. 1 of 40 patients [2.5%]; p= 0.02). Of the 32 patients with DVT, 11 patients developed a thrombosis at the site of a central venous catheter and 21 patients developed DVT at distant sites. One of these patients also had a nonfatal pulmonary embolism. These data suggest that MM patients treated with thalidomide and doxorubicin have an increased risk for DVT. (Zangari M, et al. Blood 2002;100:1168-1171) |
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