Low Risk of Infectious Events in Patients (Pts) with Chronic Myeloid Leukemia (CML) in Chronic Phase (CP) Treated with Dasatinib.
Authors: Al -Ameri Ali M , Kantarjian Hagop , Burton Elizabeth , O'Brien Susan , Ravandi Farhad , Borthakur Gautam , Walker Brenda , Rios Mary Bath , Cortes Jorge 
Published: October 2019

Abstract
Abstract 3291
Poster Board III-1

Background:
In vitro, dasatinib inhibits proliferation of CD8+ T cells in a dose-dependent manner, associated with decreased secretion of interferon-gamma and granzyme B, as well as arrest of CD8+ T cells in the G0/G1 phase of cell cycle (Blake SJ Blood 2008 Feb.1;111(3):1366-77)). Inhibition of CD8+ T cells has also been shown in blood samples from patients receiving dasatinib compared with their T cell status prior to dasatinib (Cara K.Fraser, Ex.Hema.2009; 37:256-265). These immunosuppressive properties have raised concerns about potential high risk for opportunistic and other infections among patients treated with dasatinib.

Aim:
Investigate the frequency and characteristics of infectious events in pts with CML in CP treated with dasatinib.

Methods:
Records from 55 consecutive patients with CML CP treated with dasatinib after imatinib failure were analyzed. Median time from diagnosis to the start of dasatinib therapy was 66 months. The characteristics and management of infectious complications were analyzed for each pt.

Results:
After a median follow-up of 6 months from the start of therapy, 31 (56%) pts had 53 episodes of infections (Table 1). These included 20 of 34 (58.8%) pts treated with a total daily dose of 140 mg/day, 6 of 8 (75%) treated with 100 mg/day, 2 of 3 (66.7%) treated with 70 mg/day. The one pt treated with 180 mg/day and both patients treated with a dose of 30 mg/day or less (in phase I study) had infections. Most of the infections were localized and not considered related to dasatinib therapy. Blood cultures were done for 5 of the infections (9.4%): 3 were negative and 2 positive (one for coagulase negative staphylococcus and one for streptococcus). Wound cultures were done in 3 pts: one with positive staphylococcus of the foot, one with staphylococcus positive bursitis of the elbow, and one cellulitis with a positive result for MRSA. Other positive cultures included one with a sputum culture positive for MRSA and one with E .coli in a urine culture. 29 (54.7%) of the infectious events required antibiotic therapy; 3 required IV antibiotics, (one with cellulitis, one with an ear infection and one with pneumonia) and one pt needed antiviral treatment for H. zoster. Four patients needed hospital admission; 2 pts had pneumonia, one had cellulitis and positive blood culture, and one had fever and plural effusion. Infections resolved in all 31 pts without complications. ANC at the time of infection was <1 ×109/L in 3 patients (5.5%).

Conclusions:
This analysis shows that although many patients may develop infections during the course of therapy with dasatinib, these are overwhelmingly common infections, minor, and not related to dasatinib therapy. Opportunistic infections were rare. There is no evidence that dasatinib induces a significant risk of infections in patients with CML in CP.

Disclosures:
Kantarjian: BMS: Research Funding. Rios:BMS: Honoraria. Cortes:BMS: Research Funding.