Interferon-alpha 2b (IFN alpha) for early-phase chronic lymphocytic leukaemia with high risk for disease progression: results of a randomized multicentre study.
The efficacy of interferon-alpha 2b (IFN alpha) to prolong progression-free (PFS) and/or overall survival (OS) in early B-CLL (Binet stage A) was examined in a risk-adapted phase III study. 99 previously untreated B-CLL patients were recruited. 44 patients with expected high risk for disease progression, defined by non-nodular bone marrow infiltration and lymphocyte doubling time < or = 12 months or serum thymidine kinase levels > or = 5 U/I, were randomized to either receive IFN alpha (group 1, n = 21) or not (group 2, n = 23). 55 low-risk patients were observed to evaluate this risk stratification (group 3). During a median observation time of 36 months, four patients in the IFN alpha group achieved a partial remission (PR), no patient had stable disease (SD), and 17 patients experienced progressive disease (PD). The four responders had less extensive disease at study entry and tended to exhibit a rise in serum IgG levels. In group 2, no PR, seven SD and 16 PD, whereas in group 3, no PR, 37 SD and 18 PD occurred. PFS in group 1 (6.7 months) was not different from group 2 (13.3 months, P = 0.22), but PFS of groups 1 and 2 differed from group 3 (37 months, P < or = 0.001). OS was 44.9 months (group 1), 43.1 months (group 2) and 57.9 months (group 3). OS was not significantly different for group 1 v 2, but was significant between groups 1 and 3 (P = 0.023). The higher percentage of PD in group 2 compared to group 3 (70% v 29%) shows that the selected risk factors allow the definition of CLL stage A patients at risk for disease progression within about a year. In conclusion, our data indicate that IFN alpha does not prolong PFS or OS in stage A CLL patients with high risk for disease progression.
Langenmayer
I
I
Abteilung für Hämatologie und Onkologie, Klinikum Innenstad, Ludwig-Maximilians-Universität München, Germany.
Nerl
C
C
Knauf
W
W
Dempster
S
S
Hallek
M
M
Adorf
D
D
Dietzfelbinger
H
H
Busch
R
R
Ziegler-Heitbrock
H W
HW
Thiel
E
E
Emmerich
B
B
D000368:Aged; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012307:Risk Factors
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins