Pneumonia in Patients with Chronic Lymphocytic Leukemia Treated with Venetoclax-Based Regimens: A Real-World Analysis of the Polish Adult Leukemia Group (PALG).

Background/objectives: Patients with chronic lymphocytic leukemia (CLL) are susceptible to infections that can affect their clinical outcomes.

Aims: The aims of this study were to assess the following: (1) the incidence of pneumonia in CLL patients treated with venetoclax-based regimens in a real-world setting, (2) the risk factors for event-free survival (EFS), and (3) overall survival (OS).

Methods: This multicenter study included 322 patients from eight centers. Univariable and multivariable analyses (MVA) were performed, with the development of pneumonia during venetoclax-based treatment and OS as outcomes.

Results: The most common complication was neutropenia (59%). During treatment with venetoclax-based regimens, 66 (20%) patients developed pneumonia-50 (23%) patients in the rituximab-plus-venetoclax (R-VEN) group and 13 (16%) patients in the obinutuzumab-plus-venetoclax (O-VEN) group ( = 0.15). Chronic obstructive pulmonary disease (COPD)/asthma, splenomegaly, elevated creatinine, and anemia < 8 g/dL were the risk factors for EFS in MVA (HR = 2.08, 95%CI 1.16-3.74, = 0.014; HR 1.73, 95%CI 1.08-2.78, = 0.02; HR 2.13, 95%CI 1.10-4.11, = 0.03, HR 3.58, 95%CI 2.18-5.89, < 0.001, respectively). Relapsed/refractory (R/R) CLL patients treated with R-VEN with pneumonia had worse OS than those without ( < 0.001). In patients treated with O-VEN, median OS did not differ between patients with and without pneumonia ( = 0.45).

Conclusions: Our real-world study showed that pneumonia during venetoclax treatment occurs more frequently than reported in registration trials and has a negative impact on OS, especially in patients with R/R CLL who are treated with R-VEN. Neutropenia is not a risk factor for pneumonia.