TY - JOUR
T1 - Prolonged subcutaneous administration of recombinant α2b interferon in patients with previously untreated Philadelphia chromosome-positive chronic-phase chronic myelogenous leukemia
T2 - Effect on remission duration and survival: Cancer and leukemia group B study 8583
AU - Ozer, Howard
AU - George, Stephen L.
AU - Schiffer, Charles A.
AU - Rao, Kathleen
AU - Rao, P. Nagesh
AU - Wurster-Hill, Doris H.
AU - Arthur, Diane D.
AU - Powell, Bayard
AU - Gottlieb, Arlan
AU - Peterson, Bruce A.
AU - Rai, Kanti
AU - Testa, Joseph R.
AU - Lebeau, Michelle
AU - Tantravahi, Ramana
AU - Bloomfield, Clara D.
PY - 1993/11/15
Y1 - 1993/11/15
N2 - We investigated whether recombinant α2b Interferon (rα2bIFN) 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 rα2bIFN at 5 × 106IU/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 rα2bIFN (≥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 ≤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 rα2bIFN 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 rα2bIFN 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 rα2bIFIM therapy in Ph-positive chronic-phase CML must await the outcome of randomized trials comparing IFN with conventional agents.
AB - We investigated whether recombinant α2b Interferon (rα2bIFN) 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 rα2bIFN at 5 × 106IU/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 rα2bIFN (≥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 ≤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 rα2bIFN 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 rα2bIFN 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 rα2bIFIM therapy in Ph-positive chronic-phase CML must await the outcome of randomized trials comparing IFN with conventional agents.
KW - Adolescent
KW - Adult
KW - Aged
KW - Female
KW - Humans
KW - Interferon alpha-2
KW - Interferon-alpha/administration & dosage
KW - Karyotyping
KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
KW - Leukemia, Myeloid, Chronic-Phase/genetics
KW - Male
KW - Middle Aged
KW - Prognosis
KW - Recombinant Proteins/therapeutic use
KW - Remission Induction
KW - Survival Rate
KW - Time Factors
UR - http://www.scopus.com/inward/record.url?scp=0027361154&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:A1993MH01000007&DestLinkType=FullRecord&DestApp=WOS
M3 - Article
C2 - 8219189
SN - 0006-4971
VL - 82
SP - 2975
EP - 2984
JO - Blood
JF - Blood
IS - 10
ER -