Efficacy and safety of high-dose caspofungin in the salvage therapy of pulmonary aspergillosis

Author:

YK Jiang, LP Huang, CW Yip, JH Cheng, CX Que, HZ Zhao, X Wang, LP Zhu,
LH Zhou

Author address:

Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China

Full conference title:

9th Advances Against Aspergillosis and Mucomycosis

Date: 26 February 2020

Abstract:

Purpose: To investigate the clinical efficacy and safety of high-dose caspofungin (70 mg/d) as salvage therapy for both invasive and chronic pulmonary aspergillosis.

Methods: Twenty-three patients with proven or probable pulmonary aspergillosis, who were refractory to or intolerant of prior antifungal therapies and received at least 7 days of caspofungin (70 mg/d) as salvage therapy were eligible for enrollment. Pulmonary aspergillosis was defined as either “acute”, “subacute” or “chronic” types as described by the guideline for diagnosis and management of Chronic pulmonary aspergillosis. The study was conducted from June 2014 to October 2018 in Huashan Hospital, Fudan University (a tertiary health care center in Shanghai), and characteristics, clinical efficacy, adverse reactions and outcomes were evaluated.

Results: Three proven and 20 probable pulmonary aspergillosis cases were enrolled, of whom 4 were acute invasive pulmonary aspergillosis, 7 were subacute and 12 were chronic pulmonary aspergillosis. The main predisposing conditions included pulmonary tuberculosis and chronic obstructive pulmonary disease (30% each), diabetes mellitus (26%), steroids or immunosuppressant use (22%), solid organ tumors (22%), solid organ transplantation (13%), autoimmune diseases (9%) and hematological malignancy (9%). Predisposing factors co-existed in 16 patients (70%). Most patients received high-dose caspofungin monotherapy (17/23, 74%) and 6 received caspofungin-based antifungal combination therapy. The mean duration of high-dose caspofungin treatment was 80 days (range 27-210 days). At week 12, the overall response rate was 73% (16/22) with 1 complete response and 16 partial responses, whereas 4 patients (18%) had a stable disease, 1 (5%) had progressive infection and 1 (5%) patient died. In 4 patients with acute invasive pulmonary aspergillosis, 2 had a partial response, and 6 and 8 cases in subacute and chronic types achieved favorable responses, respectively. Patients receiving caspofungin monotherapy and combination therapy had response rates of 69% (11/16) and 83% (5/6), respectively. Response rates did not significantly differ by age, gender, or weight. However, favorable response rates were significantly higher in patients with hypoproteinemia than with normal serum albumin levels (93% vs 50%; P = 0.04). After a median follow up of 13 months (range, 12 to 33 months), 19 patients (86%) were alive with 1 patient lost to follow-up. The all-cause mortality was 3 (14%) and no patients died of pulmonary aspergillosis. In all 22 patients included in the safety analysis, no patients discontinued caspofungin therapy due to drug interactions. Six (27%) patients experienced hepatotoxicity, of whom only 1 liver transplantation case had severe hepatotoxicity (grade 3 on CTCAE), and an immune rejection rather than drug toxicity was consequently confirmed by liver biopsy. Additionally, we evaluated the incidence of hepatotoxicity in the same population after adjustment of Child-Pugh scoring. The number of patients who had hepatotoxicity was noted in 27% (4/15) and 29% (2/7) in Child A and Child B class, respectively, and no statistical difference was found between 2 classes (P = 1.0).

Conclusion: High-dose caspofungin showed efficacy and safety for both invasive and chronic pulmonary aspergillosis.

Abstract Number: 17

Link to conference website:

Link Conference abstract: 

AAAM 2020

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