Background: Idelalisib, the first in class PI3K inhibitor, plus rituximab (IDL-R) is an effective targeted therapeutic option for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) but limited by treatment-re- lated adverse events (AEs). In particular, an increased rate of infections has been described in patients treated with IDL-R. Recently, a prognostic score to define the infectious risk has been developed in patients treated with ibrutinib therapy, based on the previous history of pneumonia, ≥ 2 lines of therapy and the presence of chronic obstructive pulmonary dis- ease (COPD). Aims: This study was aimed at defining the incidence, prognostic im- pact of infections and the infection risk score in CLL patients treated with IDL-R. Methods: We included 109 CLL patients who received IDL-R diag- nosed and managed in 16 Italian CLL campus centers between 2013 and 2020. All patients were treated with IDL-R. Infectious events considered were bacterial pneumonia (PN), grade ≥ 3, non-opportunistic infections (NOIs) and opportunistic infections (OIs). Results: The median age of patients was 71 years, Rai stage III-IV was present in 53.2% of patients, unmutated IGHV in 63.3%, and TP53 dis- ruption (del17p, and or TP53 mutation) in 55%. Sixty-one % of patients received ≥ 2 prior treatments; 31.2% of patients had a severe infection in the year before starting IDL-R and 29.4% a COPD. Pneumonia or a severe infectious event was recorded in 44% of patients. Patients who experienced PN or a severe infection showed a significantly inferior overall survival (OS) than those infection-free (p=0.0371). According to the scoring system, 59%, 16% and 26% of patients were included in the low (LRG), intermediate (IRG) and high-risk group (HRG), respectively The score system identified patients with an increasing rate of infections: 30% in the LRG (3% PN, 16% NOI, 11% OI), 41% in the IRG (24% PN, 12% NOI, 6% OI) and 79% in the HGR (54% PN, 14% NOI, 11% OI). The infection rate of patients in the HRG was significantly higher than that of the LRG (p<0.001) and IRG (p=0.023). The 3-year OS from start IDL-R was 66.6%, 58.7% and 42.5% for LRG, IRG and HRG, re- spectively (p=0.0371). Summary/conclusion: IDL-R was associated with the development of a relevant number of infectious events, which negatively impacted on the outcome of patients. The infection risk score developed in patients treated with ibrutinib could identify patients who might better benefit from IDL-R therapy.
VALIDATION OF AN INFECTION RISK SYSTEM IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA TREATED WITH THE IDELALISIB-RITUXIMAB REGIMEN
F. M. Quaglia;
2022-01-01
Abstract
Background: Idelalisib, the first in class PI3K inhibitor, plus rituximab (IDL-R) is an effective targeted therapeutic option for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) but limited by treatment-re- lated adverse events (AEs). In particular, an increased rate of infections has been described in patients treated with IDL-R. Recently, a prognostic score to define the infectious risk has been developed in patients treated with ibrutinib therapy, based on the previous history of pneumonia, ≥ 2 lines of therapy and the presence of chronic obstructive pulmonary dis- ease (COPD). Aims: This study was aimed at defining the incidence, prognostic im- pact of infections and the infection risk score in CLL patients treated with IDL-R. Methods: We included 109 CLL patients who received IDL-R diag- nosed and managed in 16 Italian CLL campus centers between 2013 and 2020. All patients were treated with IDL-R. Infectious events considered were bacterial pneumonia (PN), grade ≥ 3, non-opportunistic infections (NOIs) and opportunistic infections (OIs). Results: The median age of patients was 71 years, Rai stage III-IV was present in 53.2% of patients, unmutated IGHV in 63.3%, and TP53 dis- ruption (del17p, and or TP53 mutation) in 55%. Sixty-one % of patients received ≥ 2 prior treatments; 31.2% of patients had a severe infection in the year before starting IDL-R and 29.4% a COPD. Pneumonia or a severe infectious event was recorded in 44% of patients. Patients who experienced PN or a severe infection showed a significantly inferior overall survival (OS) than those infection-free (p=0.0371). According to the scoring system, 59%, 16% and 26% of patients were included in the low (LRG), intermediate (IRG) and high-risk group (HRG), respectively The score system identified patients with an increasing rate of infections: 30% in the LRG (3% PN, 16% NOI, 11% OI), 41% in the IRG (24% PN, 12% NOI, 6% OI) and 79% in the HGR (54% PN, 14% NOI, 11% OI). The infection rate of patients in the HRG was significantly higher than that of the LRG (p<0.001) and IRG (p=0.023). The 3-year OS from start IDL-R was 66.6%, 58.7% and 42.5% for LRG, IRG and HRG, re- spectively (p=0.0371). Summary/conclusion: IDL-R was associated with the development of a relevant number of infectious events, which negatively impacted on the outcome of patients. The infection risk score developed in patients treated with ibrutinib could identify patients who might better benefit from IDL-R therapy.
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