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Infectious complications in cancer patients treated with dasatinib (BMS-354825)

Abstract number: P1760

Ahmed S., Rodriguez G., Ejaz S., Al Akhrass F., Safdar A.

Background: Tyrosine kinase inhibitors (TKI) interrupt T-cell receptor mediated T-cell proliferation, activation and selective inhibition of memory CTL responses without affecting primary T or B cell responses. Few cases of cytomegalovirus (CMV), varicella-zoster virus (VZV) and Parvovirus B19 infections have been reported during dasatinib therapy. However, the true spectrum of infections in patients receiving this TKI remains unknown. To this effect, we evaluated all infections during dasatinib therapy in patients at our tertiary care cancer centre.

Methods: This retrospective analysis of infections in 57 patients during dasatinib therapy alone or in combination with other antineoplastic regimens during May 2006 through December 2007 was performed after obtaining IRB approval. The values are presented as median±s.d. Categorical data was analyzed using Chi-square.

Results: Forty-two episodes of infection were identified in 28 patients (49%) including 19 episodes (42%) during neutropenia; please refer to the table below. Duration of chemotherapy was 135±191 days in patients who developed infection vs. 228±347 days in who no infection occurred. There were no significant differences in age, race or prior haematopoietic stem cell transplantation in patients who developed infection vs. patients with no infection (n = 29; 51%). In patients who developed infections vs. who did not, had more co-morbidities including diabetes (32% vs. 14%; P =0.04); had Ph+ acute lymphocytic leukaemia (ALL; 39% vs. 10%; P = 0.01); had received high-dose steroids (50% vs. 21%; P = 0.02), and frequently received dasatinib with another antineoplastic agent(s) (54% vs. 28%; P = 0.04). Dasatinib was discontinued due to adverse events in 24% of patients with infection vs. 16% with no infection. Overall mortality was higher in patients with infection (61%) compared with 24% in patients with no infection (P = 0.08). In only one patient infection was considered as the cause of death.

Conclusions: Infections were common in patients receiving dasatinib therapy and significantly more frequently seen in patients with ALL being treated with steroids and multiple antineoplastic agents.

Table. Type of infection episodes in 26 patients during dasatinib therapy

Infection episodesn (%)
Total infection episodes42 (100)
Clinical documented infections23 (55)
Clinical pneumonia (bacterial)11 (26)
Possible fungal pneumonia4 (10)
Soft tissue infection*3 (7)
Gastroenteritis/mucositis**3 (7)
Febrile neutropenia (cause not identified)1 (2)
Urinary tract infection1 (2)
Microbiological documented infections19 (45)
Gram-positive bacterial infections12 (29)
  Clostridium difficile colitis(14)
  CoNS CrBSI1 (2)
  Enterococcus CrBSI2 (5)
  MRSA CrBSI2 (5)
  MRSA otitis extema1 (2)
Gram-negative bacterial infections4 (10)
  Klebsiella spp. neutropenic enterocolitis2 (5)
  Pseudomonas spp. CrBSI1 (2)
  Pseudomonas spp.–Klebsiella spp. urinary tract infection1 (2)
Viral infections 
  RSV pneumonia1 (2)
  HSV oral labial1 (2)
Fungal infection 
  Candida krusei CrBSI1 (2)
*2 cellulites/1 perirectal abscess; **1 neutropenic enterocolitis.
CrBSI: catheter-related bloodstream infection; CoNS: coagulase-negative staphylococci; MRSA: methicillin resistant Staphylococcus aureus.

Session Details

Date: 16/05/2009
Time: 00:00-00:00
Session name: 19th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Helsinki, Finland, 16 - 19 May 2009
Presentation type:
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