INTERFERON-ALPHA-2B (IFN-ALPHA) FOR EARLY-PHASE CHRONIC LYMPHOCYTIC-LEUKEMIA WITH HIGH-RISK FOR DISEASE PROGRESSION - RESULTS OF A RANDOMIZED MULTICENTER 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 untrea ted B-CLL patients were recruited. 44 patients with expected high risk for disease progression, defined by non-nodular bone marrow infiltrat ion and lymphocyte doubling time less than or equal to 12 months or se rum thymidine kinase levels greater than or equal to 5 U/l, were rando mized to either receive IFN alpha (group 1, n=21) or not (group 2, n=2 3). 55 low-risk patients were observed to evaluate this risk stratific ation (group 3). During a median observation time of 36 months, four p atients in the IFN alpha group achieved a partial remission (PR), no p atient had stable disease (SD), and 17 patients experienced progressiv e disease (PD). The four responders had less extensive disease at stud y 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 less than or equal to 0.001). OS was 44.9 months (group 1), 43.1 months (group 2) and 57.9 months (group 3). OS was not signif icantly 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 t o group 3 (70% v 29%) shows that the selected risk factors allow the d efinition of CLL stage A patients at risk for disease progression with in 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 disea se progression.