DP032 | CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND PREVIOUS PNEUMONIA HAVE AN IMPACT ON INFECTIOUS COMPLICATIONS IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA TREATED WITH ACALABRUTINIB AND ZANUBRUTINIB: A MULTICENTRE SEIFEM STUDY.

Infections are a major source of morbidity and mortality in patients (pts) with Chronic Lymphocytic Leukemia (CLL). The aim of our study is to describe in a real-world setting the infectious complications in pts with CLL treated with second generation Bruton’s Tyrosine Kinase inhibitors (BTKis) Acalabrutinib (Acala) and Zanubrutinib (Zanu), and to identify additional factors of infectious risk. This retrospective multicenter analysis was conducted on 460 CLL pts: 324 treated with Acala and 136 with Zanu. Pts of the second group were older, more frequently had TP53mut, pulmonary and renal impairment, more advanced Rai stage and more often already treated. We recorded 164 infections in Acala, occurred in 110 pts (34%) with an occurrence rate of 0.51. G3-G4 infections were 47 in 41 pts (12.7%) with an occurrence rate of 0.14. We recorded 71 infections in Zanu, occurred in 49 pts (36%) with an occurrence rate of 0.52. G3-G4 infections were 15 in 13 pts (9.6%) with an occurrence rate of 0.11. We registered a trend toward an earlier median time to infection with Zanu (4.5 months vs 8.2 months, p=0.068) and a significant median time to infections G3-G4 with Zanu (3.1 months vs 7.8 months, p=0.025) If considering only G3-G4 infections, risk factors for infection in Acala were COPD and pneumonia in the previous 12 months (p<0.001), in Zanu only pneumonia in the previous 12 months (p<0.001). Stratifying pts according to COPD and previous pneumonia in the last 12 months we obtained 3 groups, significantly different in terms of risk for infection (p <0.001; figure 1). The cumulative incidence of infection was 89.4% in the first year if pts showed both characteristics. We recorded a 5-year overall survival (OS) of 71,2% per Acala with 35 deaths, of whom 16 due to infections. For Zanu a 5-y OS of 80.0% with 9 deaths, of whom 4 due to infections. Acala was withdrawn for infections in 38 pts (34.5%), in 7 was definitive (6 pneumonia and 1 sepsis). Zanu was withdrawn for infections in 12 pts (24.5%), in 1 was definitive due to pneumonia. This large study showed a mild rate of infections, mostly G1-G2. We found risk factors for G3-G4 infections COPD and previous pneumonia, confirming the role of these risk factors already described with venetoclax associated to anti-CD20 antibody in previous analysis from SEIFEM (Autore et al., AJH 2024). We could consider selecting patients on BTKis with COPD and previous pneumonia to be better and more closely monitored.