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Prolonged subcutaneous administration of recombinant alpha 2b interferon in
patients with previously untreated Philadelphia chromosome-positive
chronic-phase chronic myelogenous leukemia: effect on remission duration
and survival: Cancer and Leukemia Group B study 8583 [see comments]
H Ozer, SL George, CA Schiffer, K Rao, PN Rao, DH Wurster-Hill, DD Arthur, B Powell, A Gottlieb and BA Peterson
Division of Medical Oncology, University of North Carolina at Chapel Hill
27599.
We investigated whether recombinant alpha 2b interferon (r alpha 2bIFN)
would reduce the proportion of bone marrow Philadelphia chromosome (Ph)
cells in chronic-phase chronic myelogenous leukemia (CML) by treating 107
previously untreated patients daily with r alpha 2bIFN at 5 x 10(6)IU/m2
subcutaneously. Patients with complete remission, partial remission, or
partial hematologic remission received treatment until progression; those
with progressive disease were taken off study and observed for survival.
Sixty-three (59%) of the patients achieved at least a partial hematologic
remission (24 complete remissions and 39 partial remissions). The median
time to response for the 63 responders was 3.4 months, with a median
duration of remission of 52 months and with 81% of responders continuing in
remission beyond 12 months. The median survival for the 107 patients was 66
months. Of 78 patients with cytogenetic follow-up data, 31 (40%) achieved a
partial cytogenetic response (n = 17) or a complete cytogenetic response (n
= 14). The percentage of cytogenetic responders among all patients was 29%
(31 of 107 patients). The median time to first cytogenetic response was 9
months. A major dose reduction of r alpha 2bIFN (> or = 50%) was
required at some time during treatment in 38% of patients, 26% required 10%
to 49% dose reductions, and 36% had minor dose reductions of < or = 10%.
No association was observed between dose received and the attainment of a
cytogenetic response. None of the usual prognostic factors (sex, race,
performance status, weight loss, time from diagnosis to treatment,
hepatosplenomegaly, age, symptoms, hemoglobin, or platelet, blast,
basophil, or white blood cell count) were significantly related to
survival. These data provide confirmation that major cytogenetic responses
to prolonged administration of subcutaneous r alpha 2bIFN occur in 20% to
38% (95% confidence interval) of chronic- phase Ph-positive patients.
Although it is hypothesized that patients achieving major cytogenetic
responses to r alpha 2bIFN should have prolonged remission duration and
survival compared with nonresponders, analyses of the effect of cytogenetic
responders by both "landmark" and time-dependent covariate techniques fail
to provide statistically significant evidence for an effect of cytogenetic
response on remission duration or survival. This may be due in part to an
effect size insufficiently large to be detected with the number of patients
treated in this study. Thus, confirmation of remission duration or survival
benefit, if any, of r alpha 2bIFN therapy in Ph-positive chronic-phase CML
must await the outcome of randomized trials comparing IFN with conventional
agents.
Volume 82,
Issue 10,
pp. 2975-2984,
11/15/1993
Copyright © 1993 by The American Society of Hematology
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