PS1154 INFECTIONS IN CLL PATIENTS RECEIVING IBRUTINIB: INCIDENCE AND PREDISPOSING FACTORS
Authors: Dmitrieva E. , Nikitin E. , Markova E. , Dmitrieva N. , Ptushkin V. 
Published: June 2019

Background:

Infections are a typical complication of chronic lymphocytic leukemia (CLL). Guidelines for prevention of infections in patients with CLL receiving ibrutinib is lacking, possibly due to a paucity of data in the literature.

Aims:

To analyze factors associated with severe bacterial, viral and fungal infections in CLL patients receiving ibrutinib.

Methods:

Data on bacterial, viral and fungal infections in CLL patients, who received ibrutinib during 3,6‐year period from May 2015 to December 2018 in a single centre are presented. Infections were graded according to CTCAE criteria, version IV. Cumulative incidences of infections were estimated according to Kaplan‐Meier and comparison between groups was performed using Hazard Ratios and CIs obtained from Cox regression models.

Results:

The study included 240 CLL patients. The median age was 65 years (range 32–91 years), 154 (64%) were male, 117 (48%) had stage C, 65 (27%) had ECOG status ≥ 2. Two hundred four patients (85%) received ibrutinib as monotherapy, 36 (15%) along with monoclonal antibodies to CD20. The median follow‐up was 14.8 months (range 1 ‐ 44 months). Most patients (224, 93%) received ibrutinib for relapse with a median number of previous treatment lines of 3 (range 1–12). Neutropenia (defined as <1000 cells/mkl) prior to ibrutinib was found in 20 patients (8%). Steroid hormones were given to 20 patients. A total of 525 infectious episodes were recorded in 183 patients. Of these, 381 (72.5%) episodes were bacterial/mixed infections, 115 (22%) viral and 29 (5.5%) fungal infections. Among bacterial infections 121 (32%) were scored as grade III, 43 (11%) as grade IV and 7 (1,8%) infections were fatal. The overall cumulative incidence of grade III‐V bacterial infections during 12 months was 37% (95% CI 31–43%), viral infections ‐ 28% (95% CI 22–34), and fungal infections 8% (95% CI 4–12). There was a significantly (p < .05) higher cumulative incidence of grade III‐V bacterial infections in patients with ≥3 lines of prior therapy (HR: 2.0; 95% CI 1.36–2.97), Binet stage C (HR: 1.4; 95% CI 0.95–2.08), ECOG ≥ 2 (HR: 2.4; 95% CI 1.6–3.6), baseline neutropenia (HR: 1.25; 95% CI 0.73–2.13), as well as in males (HR: 1.8; 95% CI 1.16–2.8, p = 0.004). In a multivariate analysis male gender (RR 1.89, 95% CI 0.5–3, p = 0.006), ECOG ≥ 2 (RR = 1.97, 95% CI 0.5–3) and initial neutropenia (RR = 1.76, 95% CI 0.99–3.1) were significant and independent risk factors. Cumulative incidence of any fungal infections was associated with simultaneous use of corticosteroids (HR: 6; 95% CI 5.85–14,7) and baseline neutropenia (HR: 2.36; 95% CI 0.95–5.85). The only parameter significantly associated with viral infections was ≥3 lines of prior therapy (HR: 1.74; 95% CI 1.06–2.86). As 160 (87%) patients experienced >1 episode of infections, we compared rates of infections expressed as number per 100 patient‐months. Grade III‐V bacterial infections were significantly associated with ≥3 lines of previous therapy (3,6 vs 2,3), ECOG ≥ 2 (5,72 vs 2,27), male gender (3,2 vs 2,03) and stage C (3,8 vs 2,24). Fungal infections were more frequently observed in patients with a history of >3 lines of treatment (0,87 vs 0,31), initial neutropenia (1,75 vs 0,47), simultaneous use of steroids (1,96 vs 0,39).

Summary/Conclusion:

Patients with ECOG status >2 and initial neutropenia are at highest risk of severe bacterial infections and may benefit from antibacterial prophylaxis. Antifungal prophylaxis can be considered in patients who receive corticosteroid hormones simultaneously with ibrutinib