Interferon‐alpha 2b (IFNα) for Early‐Phase Chronic Lymphocytic Leukaemia with High Risk for Disease Progression: Results of a Randomized Multicentre Study

Abstract

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.

Aberrant interferon-signaling is associated with aggressive chronic lymphocytic leukemia

“…6 Our results also suggest that inhibiting the activation of STAT3 with small molecule TYK2 inhibitors (Figure 7) or possibly antioxidants ( Figure 5) might be a strategy to improve the therapeutic efficacy of IFN-␣2b in patients with more aggressive disease.…”

“…4,5 Exogenous IFN also has therapeutic activity in CLL, particularly in patients with low risk disease. 6 However, IFN is generally inactive in more aggressive disease, and may even accelerate tumor growth, 7 suggesting that IFN-signaling may be altered in tumor cells from such patients.…”

B‐chronic lymphocytic leukemia: practical aspects

“…266x275 However, in a small randomized trial interferon-a did not affect progression-free survival in Binet stage A patients with a high likelihood of disease progression. 275 A beneficial effect on 'smouldering' CLL as well as a role in the improvement of immunoglobulin levels cannot be excluded. 275 …”

“…275 A beneficial effect on 'smouldering' CLL as well as a role in the improvement of immunoglobulin levels cannot be excluded. 275 …”

Resveratrol has anti-leukemic activity associated with decreased O-GlcNAcylated proteins

“…Type I interferons (IFNs) have been used in the treatment of cancer for many years [1], but their activity in acute myeloid and chronic lymphocytic leukemia (CLL) is limited [2,3]. Previously, we found that IFN-signaling is corrupted in clinically aggressive CLL cells, resulting in prolonged phosphorylation and activation of the oncogenic signal transducer and activator of transcription 3 (STAT3) [4].…”