|
|
BioOncology Watch Timely Information for Practicing
Physicians |
|
|
november 2003 CHRONIC MYELOID
LEUKEMIA (CML) Major molecular
responses. Tim
Hughes and colleagues of the International Randomized Study of Interferon
versus STI571 (IRIS) Study Group utilized real-time quantitative PCR to
measure the level of BCR-ABL transcripts in the blood of patients when they
first attained a complete cytogenetic remission and at subsequent times to assess
patterns of response and determine the prognostic value of a molecular
response. In the IRIS trial, 1106
patients with CML in chronic phase were randomized to receive imatinib or
interferon alfa plus cytarabine. The
study design and treatment plan have been reported previously (N Engl J Med 2003;348:994-1004). After 12 months of treatment, 68% of
patients in the imatinib group and 7% of patients in the interferon plus
cytarabine group had achieved complete cytogenetic remission. Among these patients with complete
cytogenetic remissions, levels of BCR-ABL transcripts had decreased by ³
3 logs in 57% of imatinib-treated patients compared to 24% of interferon plus
cytarabine-treated patients (p <0.003).
The probability of remaining progression-free at 24 months was 100%,
95%, and 85% (p<0.001) for patients who at 12 months had the following
responses to therapy: 1) complete cytogenetic remission and a reduction of
BCR-ABL transcript levels of ³ 3 logs; 2)
complete cytogenetic remission and a reduction of BCR-ABL transcript levels
of <3 logs; and 3) less than a complete cytogenetic remission,
respectively. An estimated 39% of
patients treated with imatinib compared to only 2% of patients treated with
interferon plus cytarabine had a reduction in BCR-ABL transcript levels of ³
3 logs (p <0.001). The results of
this study show that patients who had a reduction in the level of blood BCR-ABL
transcripts of ³ 3 logs had a negligible risk of
disease progression over the following 12 months. The authors propose that a reduction of ³
3 logs in BCR-ABL transcript blood levels be used to define a major molecular
response in CML. (Hughes TP, et al. N Engl J Med 2003;349:1423-1432) NON-HODGKIN'S
LYMPHOMA
Rituximab treatment
of MALT lymphomas. Mucosa-associated
lymphoid tissue (MALT) lymphomas are associated with an indolent clinical
course, but have short progression-free survival times. Although eradication of Helicobacter
pylori with antibiotics has been shown to effectively treat localized
gastric MALT lymphoma, the therapeutic options for MALT-lymphoma patients who
have no evidence of Helicobacter pylori infection or who have
non-gastric or disseminated disease continue to include chemotherapy,
radiotherapy, and surgery. CD20
antigen is expressed on the surface of malignant cells in virtually all MALT
lymphomas; thus, Annarita Conconi and the International Extranodal Lymphoma
Study Group conducted a phase II study to evaluate the activity of rituximab
(375 mg/m2 weekly for 4 weeks) in 35 patients with previously
untreated (n = 11) and treated (n = 24) MALT lymphomas. Rituximab treatment resulted in a 73%
response rate (15 complete and 10 partial responses) and rituximab was well
tolerated. Previously untreated
patients had an 87% response rate compared to a 45% response rate for
previously treated patients (p = 0.03).
The median duration of response was 10.5 months. The median time to treatment failure was
longer in previously untreated patients (22 vs. 12 months). These results demonstrate that rituximab
has activity against CD20+ MALT lymphomas.
(Conconi A, et al. Blood
2003;102:2741-2745) High-dose
radioimmunotherapy (HD-RIT) vs. conventional high-dose therapy (C-HDT). Ajay Gopal et al.
analyzed data obtained from 125 consecutive patients with relapsed follicular
lymphoma who had been treated at the Fred Hutchinson Cancer Research Center
with either myeloablative anti-CD20 HD-RIT (131I- tositumomab)
(n = 27 patients treated in a phase I or a phase II study) or C-HDT supported
by autologous stem cell transplantation (n = 98 patients treated between 1990
and 1998). Patients treated with
HD-RIT had improved progression-free and overall survival times compared to
patients treated with C-HDT. The
estimated 5-year overall and progression-free survival rates for
HD-RIT-treated patients were 67% and 48%, respectively, and 53% and 29% for
C-HDT-treated patients, respectively.
The 100-day treatment-related mortality rates were 3.7% and 11% for
the HD-RIT and C-HDT groups, respectively and the estimated probabilities for
the development of secondary MDS/AML were similar between the 2 treatment
groups. These data indicate that
HD-RIT is an attractive alternative to C-HDT for the treatment of patients
with relapsed follicular lymphoma.
(Gopal AK, et al. Blood 2003;102:2351-2357) VACCINE THERAPY Strategies to
increase T-cell reactivity. Three
recent studies report vaccine strategies to improve anti-tumor T-cell function. Isabelle Bedrosian et al randomized 27
patients with stage IV melanoma to receive peptide-pulsed dendritic cell
vaccinations by either intravenous, intranodal, or intradermal routes of
administration. They found the
intranodal route to result in superior T-cell sensitization. Tanja Maier et al administered autologous
tumor-lysate-pulsed dendritic cell vaccinations by intranodal injections
(median of 9.5 weekly vaccinations) to 10 patients with cutaneous T-cell
lymphoma. Five patients achieved
responses (1 complete response). The
median duration of partial response was 10.5 months and the complete response
was ongoing at 19 months. Selected
patients had massive infiltration of CD8+ and TIA+ cytotoxic T cells at the
site of regressing lesions. Igor
Astsaturov and others injected 7 melanoma patients with high-dose
interferon-alpha (20 MU/m2 x 20 doses) after the completion of a
recombinant viral vaccination (expressing gp100) protocol. They found that the interferon treatment
recalled gp100-reactive T cells in patients who had previously responded to
vaccination and tumor regression was observed in 2 patients. These studies show that cancers can be
susceptible to vaccine strategies that enhance the activity of tumor-reactive
T cells. (Bedrosian I, et al. J Clin
Oncol 2003;21:3826-3835; Maier T, et al. Blood 2003;102:2338-2344; and Astsaturov I, et al. Clin Cancer Res 2003;9:4347-4355)
|
||
|
Produced by Market Development Group through an
educational grant from Genentech, Inc. and IDEC
Pharmaceuticals. Comments and inquiries can be e-mailed to webmaster@biooncologywatch.org |
||