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Targeted Therapies Formerly BioOncology Watch www.tgt-therapies.com |
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MARCH 2005 RADIOIMMUNOTHERAPY (RIT) 131I-tositumomab for previously untreated and relapsed
non-Hodgkin’s lymphoma (NHL). Anti-CD20 RIT with tositumomab followed by 131I-labeled tositumomab
(the Bexxar therapeutic regimen) has been shown to
be effective treatment for follicular lymphoma refractory to chemotherapy.
The mechanism of action of this RIT regimen probably involves both antibody-mediated effects and ionizing radiation. Mark Kaminski and coworkers
report the results of a study of a single, 1- week course of 131I-tositumomab
as initial therapy for 76 patients with stage III or IV follicular lymphoma.
High overall and complete response (CR) rates (95% and 75%, respectively)
were achieved, and the median progression-free survival (PFS) time was 6.1
years. In addition, PCR assays for BCL2 demonstrated an 80% molecular
response rate in evaluable patients who had a
clinical CR. The 131I-tositumomab treatment showed moderate hematologic toxicity. ♦ Sandra Horning and colleagues
evaluated 131I-tositumomab in patients with indolent, follicular large-cell
or transformed B-cell lymphoma who had progressive disease after rituximab (n=40). The overall response rate was 65% (38%
CR rate), and the responses to 131Itositumomab were not found to be
significantly associated with prior response to rituximab.
The median PFS time for responders was 24.5 months (it has not yet been
reached for complete responders). ♦ Julie Vose
and others conducted a phase I trial of 131I-tositumomab combined with
high-dose BEAM chemotherapy (HDC) followed by autologous
stem cell transplantation (ASCT) for patients with chemotherapy-resistant
relapsed or refractory B-cell NHL (n=23). A CR rate of 57% was achieved, and
toxicities were similar to those reported with BEAM alone. The event-free and
overall survival rates were 39% and 55%, respectively, after a median
follow-up of 38 months (range, 27–60 months). These studies show that
131Itositumomab can induce durable remissions in patients with untreated as
well as relapsed/refractory B-cell NHL. Moreover, the addition of
131I-tositumomab to HDC/ASCT is feasible. (Kaminski MS, et al. N Engl J Med 2005;352:441–449; Horning SJ, et al. J Clin Oncol 2005;23:712–719; Vose JM, et al. J Clin Oncol 2005;23:461–467) RITUXIMAB Treatment for B-cell malignancies.
Single-agent rituximab administered as 4 weekly
infusions of 375mg/m2 is effective for relapsed/refractory and previously
untreated indolent NHL and has been shown to be synergistic with cytotoxic agents. Robert Marcus et al studied previously
untreated poor risk patients with advanced follicular lymphoma who were
randomized to RCVP (rituximab plus cyclophosphamide, vincristine,
prednisone) or CVP. R-CVP patients had higher overall (81% vs 41%) and complete (57% vs
10%) response rates than those treated with CVP alone. In addition, the
median time to progression was longer in the R-CVP group (32 vs 15 months), although there was no difference in
overall survival at 30 months’ median followup. Rituximab did not increase the toxicity of CVP. ♦
Myron Czuczman and colleagues evaluated the
combination of rituximab plus fludarabine
in treatment-naïve and relapsed patients with
low-grade or follicular NHL. This combination regimen was well tolerated and
was associated with an 80% CR rate. Molecular remissions were achieved in 88%
of evaluable cases. ♦ Michele Ghielmini and associates studied single-agent rituximab therapy in patients with mantle cell lymphoma
(MCL). Patients (n=104) were randomized to the standard regimen of 4 weekly
infusions or the standard regimen plus rituximab
administration (375 mg/m2) every 8 weeks for 4 times. A clinical response
rate of 27% was achieved, and no difference in response between the treatment
arms was observed. ♦ Additionally, Steven Treon
and coworkers performed a sequence analysis of the FcγRIIIA
coding region in 58 patients with Waldenström’s macroglobulinemia who were treated with rituximab. Their findings showed FcγRIIIA-158
polymorphisms to be predictive for response to rituximab.
These studies demonstrate that rituximab in combination
with cytotoxic chemotherapy is effective therapy
for indolent B-cell malignancies, but more innovative approaches to mantle
cell lymphomas are needed. (Marcus R, et al. Blood 2005;105:1417–1423; Czuczman MS, et al. J Clin Oncol 2005;23:694–704; Ghielmini
M, et al. J Clin Oncol
2005;23:705–711; Treon SP, et al. J Clin Oncol 2005;23:474–481) BORTEZOMIB Studies in NHL. Bortezomib
is a proteasome inhibitor that has been shown to be
effective in patients with relapsed or refractory multiple myeloma. Andre Goy and associates report the results of bortezomib treatment (1.5 mg/m2 intravenous push on days
1, 4, 8, and 11 every 21 days for up to 6 cycles) of patients with relapsed
or refractory B-cell NHL (n=60). Twelve (41%) of 29 evaluable patients with
MCL achieved a response (6 partial response and 6 CR). The median time to progression
has not been reached after a median follow-up of 9.3 months. Four other
patients have responded (1 small lymphocytic
lymphoma, 1 follicular lymphoma, 1 diffuse large B-cell lymphoma, and 1 Waldenström’s macroglobulinemia).
Grade 3 thrombocytopenia, gastrointestinal adverse events, neutropenia, and peripheral neuropathy were reported in
47%, 20%, 10%, and 5% of patients, respectively. ♦ Owen O’Connor and
colleagues also studied bortezomib therapy in
patients with previously treated indolent lymphoma or MCL. Among 24 evaluable patients, the overall response rate was 58%; responses
have lasted from 3 to 24+ months. Observed grade 3 toxicities were lymphopenia (n=14) and thrombocytopenia (n=7). Thus, bortezomib is active against B-cell lymphomas and with
acceptable marrow, gastrointestinal, and neurologic
toxicity. (Goy A, et al. J Clin Oncol
2005;23:667–675; O’Connor OA, et al. J Clin Oncol 2005;23:676–684) |
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Produced by MDG Development Group through an
educational grant from Genentech, Inc. |