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Targeted Therapies Formerly BioOncology Watch www.tgt-therapies.com |
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DECEMBER
2004 NON-HODGKIN'S LYMPHOMA (NHL) Phase II study of denileukin
diftitox. Denileukin diftitox, a fusion
protein combining diphtheria toxin and IL-2 that targets lymphoma and
leukemia cells expressing the IL-2 receptor, has been shown to have activity
in CD25+ cutaneous T-cell lymphoma. Nam Dang et al evaluated the use of denileukin diftitox as therapy
in 45 patients with relapsed or refractory B-cell NHL. All patients had previously been treated
with rituximab and 32 (71%) patients were
refractory to the last chemotherapy treatment. Three CRs and 8 PRs were achieved (overall response rate of 24.5%). Objective response rates were similar in
patients with CD25+ and CD25- histologies (22% and
29%, respectively). For survivors with a median follow-up of 18 months (range, 9-28
months), the projected progression-free survival rate at 20 months was
24% (95% CI: 0%-60%). Adverse events
were low-grade and transient. This
study demonstrated that denileukin diftitox is active against both CD25+ and CD25- relapsed
or refractory B-cell NHL. Further
evaluation of this agent in combination with other therapies is
warranted. (Dang NH, et al. J Clin Oncol 2004;22:4095-4102) Rituximab plus
fludarabine, cyclophosphamide,
and mitoxantrone (FCM). Roswitha Forstpointner and colleagues report their results from a multicenter, randomized study of the combination of an rituximab plus FCM chemotherapy (R-FCM) versus FCM alone
for patients with relapsed or refractory follicular, mantle-cell, or lymphomaplasmocytoid lymphoma (N = 147). Among 128 evaluable
patients, a response rate of 79% (33% CRs and 45% PRs) was observed in R-FCM-treated patients compared to
58% (13% CRs and 45% PRs)
in FCM-treated patients (p = 0.01).
Subgroup analyses revealed that R-FCM induced higher response rates
than FCM alone in both the follicular and mantle-cell lymphoma
populations. Progression-free and
overall survival times were also greater in the R-FCM treatment group (p
=0.0381 and 0.0030, respectively).
Safety profiles were similar in both groups. This study demonstrated that the addition
of rituximab to combination FCM chemotherapy
improved outcomes in this population of relapsed or refractory NHL
patients. Caution should be used in
the interpretation of these data because FCM is a new combination instead of
a standard therapy, the study population is a heterogeneous mixture of
different NHL histologies, and there is a lack of
information regarding therapies utilized subsequent to protocol
treatment. (Forstpointner
R, et al. Blood 2004;104:3064-3071)
ACUTE MYELOID LEUKEMIA (AML) Phase III study of all-trans retinoic
acid (ATRA). RF Schlenk and others
from the AML Study Group ULM conducted a phase III study to evaluate the
effect of combining ATRA with standard chemotherapy in elderly patients with
AML. AML patients aged ≥ 61
years (median, 66.6 years) were randomized to receive induction and
consolidation chemotherapy with or without ATRA (N = 242). Induction chemotherapy consisted of ICE (idarubicin, cytarabine, etoposide) ± ATRA and consolidation chemotherapy
comprised HAM (cytarabine and mitoxantrone)
± ATRA. Patients in CR were then
randomized to a second intensive consolidation
chemotherapy or to a 1-year oral maintenance chemotherapy. Induction therapy with the ATRA-containing
chemotherapy regimen was observed to have a greater CR rate compared to
standard chemotherapy alone (52% vs. 39%; p = 0.05). Event-free and overall survival times were
also improved in ATRA-treated patients (p = 0.03 and 0.01,
respectively). Overall survival after
the second randomization was greater in the intensive consolidation group
compared to the maintenance group (p < 0.001). These findings indicate that the addition
of ATRA to standard induction and consolidation chemotherapy may improve
treatment outcomes in elderly patients with AML. (Schlenk RF, et
al. Leukemia 2004;18:1798-1803) MULTIPLE MYELOMA Donor lymphocyte infusion (DLI) plus
thalidomide. Adoptive immunotherapy with DLI has become an
accepted treatment option for multiple myeloma
patients who relapse after allogeneic stem cell
transplantation. Response rates after
DLI range from 30% to 50% and few CRs are
achieved. In the present phase 1/2
study, Nicolaus Kroger et al. added oral low-dose
thalidomide (100 mg daily) to DLI therapy to determine if this combination
would improve the antimyeloma effect of DLI in 18 myeloma patients who relapsed after allogeneic
transplantation. CR was achieved in
22% of patients and the overall response rate was 67%. Thalidomide-related grade I/II weakness was
seen in 68% of patients and grade I/II neuropathy occurred in 28% of
patients. No grade II-IV acute GvHD was observed and only 2 patients developed grade I
acute GvHD.
Limited chronic GvHD was seen in 2 patients
(11%). These findings indicate that a
strong anti-myeloma effect with a low incidence of GvHD can be induced by the combination of low-dose
thalidomide and DLI. (Kroger N, et al.
Blood 2004;104:3361-3363) WALDENSTRÖM’S MACROGLOBULINEMIA (WM) Paradoxical observations following rituximab treatments.
Rituximab is an important treatment for patients with
WM. Usual therapy consists of 4 weekly
infusions of rituximab 375 mg/m2 and
serum IgM levels are evaluated 12 weeks after treatment
begins. Steve Treon
and colleagues describe an abrupt rise in serum IgM
levels measured within 12 weeks of the start of rituximab
therapy in 10 of 11 patients treated.
The mean serum IgM levels increased from
4,370 mg/dL at baseline to a peak of 5,865 mg/dL that occurred at a mean of 4 weeks after the
initiation of treatment. Mean serum
viscosity levels also increased in 8 patients tested. A subdural
hemorrhage occurred in one patient whose rise in serum IgM
level was associated with an increase in serum viscosity from 3.9 to 10.1 centipoise. Two other patients experienced worsening
headaches and epistaxis. These data suggest that spikes in serum IgM levels commonly occur in WM patients shortly after
initiation of rituximab treatment. Careful monitoring is recommended and the
mechanism of this effect is under investigation. (Treon SP, et al.
Ann Oncol
2004;15:1481-1483) |
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