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BioOncology Watch Timely Information for Practicing
Physicians |
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APRIL
2002 Chronic Myelogenous Leukemia (CML) Response to imatinib mesylate. Hagop Kantarjian et al
administered oral imatinib 400 mg daily to 452 patients with a confirmed
diagnosis of late-chronic-phase CML that was resistant to or had relapsed
after interferon alfa therapy.
Complete hematologic and major cytogenetic responses were induced in
95% and 60% of patients, respectively.
However, the majority of patients (59%) did not achieve a complete
cytogenetic response and, after a median follow-up of 18 months, 11% of patients
had progressed to an accelerated or blast phase. The 18-month survival rate was 95%. The following baseline characteristics were identified as
independent predictors for major cytogenetic responses to imatinib: absence
of blasts in peripheral blood; <5% blasts in bone marrow; hemoglobin level
>12 g/dL; <1 year from the time of diagnosis of CML; and prior
cytogenetic response to interferon therapy.
In a second study, Moshe Talpaz et al reported sustained hematologic
responses and major cytogenetic responses in 69% and 24%, respectively, of
181 patients with a confirmed diagnosis of accelerated-phase CML. The
complete cytogenetic response rate was 17% and the estimated 12-month
progression-free and overall survival rates were 59% and 74%,
respectively. Patients received
either 400 mg (n = 62) or 600 mg (n =119) of imatinib daily. Patients in the 600 mg group were observed
to have a greater major cytogenetic response rate (28% vs. 16%) as well as
higher 12-month rates of continuing hematological response (79% vs. 57%),
freedom from disease progression (67% vs. 44%), and survival (78% vs.
65%). Thus, imatinib is an effective
treatment for both chronic-phase CML patients who were previous interferon
therapy failures, and patients with accelerated-phase CML. The data also indicate that the most
effective therapeutic dose of imatinib in the treatment of CML is not
known. Future trials to define the
optimal imatinib dose and to investigate efficacious combination therapies to
increase the complete cytogenetic response rate are needed. (Kantarjian H, et al. N Engl J Med
2002;346:645-652 and Talpaz M, et al. Blood 2002;99:1928-1937) Follicular Lymphoma Idiotype (Id)-pulsed dendritic cell (DC) vaccination. John Timmerman and associates vaccinated
35 patients with follicular B-cell lymphoma using DCs pulsed with
tumor-derived Id protein. The first
10 patients had residual or relapsed disease after previous therapy and the
remaining 25 patients were vaccinated in first remission after chemotherapy
(5 of these patients were in complete remission). Eight of the initial 10 patients with measurable disease
mounted a T-cell proliferative anti-Id response and 4 patients had clinical
responses (4 complete responses [CRs], 1 partial response [PR], and 1 molecular
response). Of the 25 patients
vaccinated in first remission, 23 completed the vaccination schedule and 15
(65%) developed T-cell or humoral anti-Id responses. With a median follow-up of 43 months, 16
of 23 patients (70%) remained free of tumor progression. Booster vaccinations were given to 6
patients who developed progressive disease and tumor regression was observed
in 3 of these patients (2 CRs and 1 PR).
These findings show that Id-pulsed DC vaccination can induce immune
responses leading to antitumor activity in patients with B-cell follicular
lymphoma, including patients with resistant or relapsed disease. Vaccine trials utilizing agents without
DCs are ongoing and may further delineate the role of Id-pulsed DC
vaccination. (Timmerman JM, et al. Blood
2002;99:1517-1526) Chronic
Lymphocytic Leukemia (CLL) Combination Campath-1H and fludarabine therapy. Ben Kennedy and colleagues combined
Campath-1H and fludarabine in 6 patients with CLL refractory to both
fludarabine and Campath-1H. Patients
who were already receiving Campath-1H at the time fludarabine was added to
the treatment regimen continued Campath-1H at a dose of 30 mg intravenously 3
times weekly. Patients for whom
Campath-1H was restarted were given an escalating-dose schedule of Campath-1H
beginning at 3 mg. Fludarabine was
administered at a dose of 25 mg/m2 intravenously for 3 days every
28 days. Responses were achieved in 5
of the 6 patients (1 CR) and complete morphologic responses were seen in 3
patients. These preliminary findings
indicate that Campath-1H plus fludarabine is a potentially promising therapy
for refractory CLL. In addition,
encouraging results from early studies of Campath-1H plus rituximab
combination therapy in patients with refractory CLL have also been recently
reported. (Kennedy B, et al. Blood 2002;99:2245-2247, Nabhan C, et al. Blood
2001;98:365a [abstract 1536], and Faderl S, et al. Blood 2001;98:365a
[abstract 1537]) Mantle-Cell Lymphoma (MCL) Induction therapy with rituximab plus CHOP. Orion Howard and coworkers conducted a
phase II study in which 40 previously untreated patients with advanced MCL
were given 6 cycles (21 days per cycle) of rituximab (375 mg/m2 on
Day 1) plus standard-dose CHOP chemotherapy. Nineteen patients (48%) achieved
either a CR (13 patients) or an unconfirmed CR (6 patients) and 19 patients
(48%) had PRs. However, 28 of 40
patients had disease progression (median progression-free survival of 16.6
months). Of 25 patients with
PCR-detectable BCL-1/IgH translocations or clonal IgH rearrangements at
baseline, 9 attained a complete molecular remission. Nonetheless, progression-free survival for
these 9 patients in molecular CR was similar to that of patients who had not
achieved molecular remission (16.5 vs. 18.8 months; p = 0.51). These results show that the responses and
molecular remissions achieved in MCL patients with rituximab plus CHOP
treatments are transient in nature.
Further studies investigating the use of rituximab plus CHOP for in
vivo purging to provide tumor-free autologous stem cells are
warranted. The addition of rituximab
to hyper-CVAD therapy for MCL is also being studied. Preliminary data shows that after a median
follow-up of 14 months a 90% 2-year survival rate has been realized. (Howard
O, et al. J Clin Oncol 2002;20:1288-1294 and Romaguera J, et al. Blood
2001;98:726a [abstract 3030]) |
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