Infectious Events In Patients with Chronic Myeloid Leukemia Treated with Nilotinib as a Front Line Therapy and After Imatinib Failure

Different tyrosine kinase inhibitors have different effect on various kinases. Dasatinib and bosutinib inhibt Src, an effect that has been suggested could have an immunosuppressive effect. Others, such as imatinib and nilotinib, have no discernible effect on Src. All agents however can cause myelosuppression. Because of these effects, and in view of long-term us of these agent, infectious complications may occur during therapy. The risk of infectious complications with nilotinib therapy has not been reported. Aim: To investigate the frequency and characteristics of infectious events in patients (pts) with chronic myeloid leukemia (CML) treated with Nilotinib as a front line therapy (FL) or after Imatinib failure (IF).

Retrospective review of medical records of patients who received Nilotinib between Jun 2004 and Jun 2010, either as FL therapy or as salvage therapy after IF.

The total number of pts treated were 169, including 90 FL pts and 79 IF pts. Overall, 132 pts (78%) were in chronic phase and 37 pts (22%) were in accelerated phase. The median age was 53 (20 - 87) years and 57% of the pts were male. Median follow up for all patients was 30 months. Among the FL therapy group, 9 (10%) pts developed any infection, whereas 29 of 79 (37%) pts treated with nilotinib after IF developed any infection. Table 1 shows the types of infections for both groups.

Of the 43 infections in the IF group, 26 (60%) were clinically documented infections (CDI), 8 FUO (19%), 3 bacterial (7%), 5 viral (12%) [Zoster (2), influenza (2), RSV (1)] and 1 (2%) fungal infections. Nine (21%) of these infectious episodes occurred with neutropenia and 24/43 episodes (56%) required hospitalization. In the FL group, 6 (60%) of the events were CDI, 2 (20%) were FUO, 1 (10%) was bacterial and 1 (10%) was viral [zoster]. None of the FL group events were associated with neutropenia and only 2/10 episodes required hospitalization. We also studied the relationship of infectious events according to the nilotinib doses at the moment of the infection. In IF group, 46% of the events occurred at 800mg/day, 30% at 400mg/day, 14% at 1200 mg/day and 10% at 200mg/day or less. In the FL group, 6 (60%) events occurred at 800mg/day and 40% at 400mg/day. There was no statistically significant association between infectious event rate and the nilotinib starting dose. Overall mortality at 30 months was 22% (29/169), 35 (44%) of the IF group died and 2 (2%) of the FL died. Three of the deaths in the IF group and none in the FT group were due to infection.

Although several patients developed infectious complications during nilotinib therapy, particularly when used after imatinib failure, these episodes were common infections that responded rapidly to adequate intervention. Atypical infections were not seen. Further research is needed to determine predisposing factor and measures to prevent infections.

Cortes:Novartis: Research Funding; BMS: Research Funding; Pfizer: Research Funding; Pfizer: Consultancy. Kantarjian:BMS, Pfizer and Novartis: Research Funding; Novartis: Consultancy. O'Brien:Novartis: Research Funding; BMS: Research Funding.