Randomized Trial of Micafungin Versus Fluconazole in Prophylaxis Against Invasive Fungal Infections in Hematopoietic Stem Cell Transplant Recipients

Silvia Park, MD1*, Kihyun Kim2, Jun Ho Jang, MD, PhD3*, Seok Jin Kim, MD.Ph.D.3*, Won Seog Kim, M.D. Ph.D.3*, Chul Won Jung, MD, PhD4, Ki Sun Jung3*, Jinhyun Cho3*, Kwai Han Yoo, MD3* and Haa-na Song3*

Author address: 

1Department of Medicine, Samsung Medical Center, Sungkyunkwan Univ. School of Medicine, Seoul, South Korea 2Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea 3Samsung Medical Center, Seoul, South Korea 4Divison of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

Abstract: 

Introduction: Invasive fungal infections cause significant morbidity and mortality in hematopoietic stem cell transplantation (HSCT) recipients. Although fluconazole has been widely used as an antifungal prophylactic agent in these patients, it is not reliably effective against mold infection including invasive aspergillosisMicafungin provides antifungal activity against Candida and Aspergillus species, and previous studies have demonstrated its efficacy when used as a prophylactic agent for fungal infection in neutropenic patients. Here, we evaluated and compared the incidence rate of proven or probable invasive fungal infections (IFIs) with antifungal prophylaxis using micafungin or fluconazole.

Methods: This is a prospective, single center, phase II study involving adult patients who received allogeneic or autologous HSCT. Patients were randomly assigned to micafungin or fluconazole arms in the ratio of 2:1, and the treatment was initiated within 24 hour of hematopoietic stem cell infusion and maintained for up to 21 days. Primary objective was the incidence of proven or probable invasive fungal infections (IFIs) during the 100 days after HSCT. Secondary objectives involved the incidence of possible, proven or probable IFIs, need for change of anti-fungal agents before engraftment, IFI-related mortality and survival within 100 days after transplantation.

Results: Between March 2010 and May 2015, a total of 257 patients were enrolled. Excluding 7 patients who did not receive at least one dose of study treatment, 250 patients (micafungin, n=165; fluconazole, n=85) were examined for clinical efficacy. The median age was 47 years (20-64) and allogeneic and autologous transplantation comprised 56.0% (n=140) and 44.0% (n=110) of the patients. Baseline characteristics were well balanced between the two groups. Overall, the incidence of proven and probable IFIs within 100 days of HSCT was 7.6% (n=19), and there was no significant difference in the proportion of patients who experienced proven or probable IFIs between the micafungin and the fluconazole groups (7.3% in micafungin group versus 8.2% in fluconazole groupp=0.786). Thirteen patients of micafungin arm (7.9%) and 8 patients of fluconazole arm (9.4%) had to have changed antifungals before engraftment (p=0.824). There was no significant difference in the mortality within 100 days after HSCT (9.1% in micafungin arm vs 12.9% in fluconazole arm, p=0.345).

ConclusionMicafungin is comparable to fluconazole in the prevention of IFIs in HSCT recipients.

 

Table. Clinical outcomes including invasive fungal infections within 100 days after transplantation

Characteristics (total n=250)

Total patients

(n=250)

Fluconazole

(n=85)

Micafungin

(n=165)

p-value

Proven IFIs

All

Candidiasis

Aspergillosis

Mucormycosis

5 (2.0%)

  2 (0.8%)

  1 (0.4%)

  2 (0.8%)

3 (3.5%)

  1 (1.2%)

  0 (0.0%)

  2 (2.4%)

2 (1.2%)

  1 (0.6%)

  1 (0.6%)

  0 (0.0%)

0.341

  1.000

  1.000

  0.115

Probable IFIs

16 (6.4%)

5 (5.9%)

11 (6.7%)

0.810

Possible IFIs

7 (2.8%)

1 (1.2%)

6 (3.6%)

0.428

Proven, probable IFIs

19 (7.6%)

7 (8.2%)

12 (7.3%)

0.786

Proven, probable, possible IFIs

26 (10.4%)

8 (9.4%)

18 (10.9%)

0.713

Invasive mold infections

 Proven, probable

 Proven, probable, possible

18 (7.2%)

25 (10.0%)

6 (7.1%)

7 (8.2%)

12 (7.3%)

18 (10.9%)

0.951

0.504

Need for anti-fungal agents change before engraftment

21 (8.4%)

8 (9.4%)

13 (7.9%)

0.824

Mortality within 100 days after HSCT

26 (10.4%)

11 (12.9%)

15 (9.1%)

0.345

IFI related mortality within 100 days

after HSCT

5 (2.0%)

3 (3.5%)

2 (1.2%)

0.341

28 invasive fungal infections were observed in 26 patients

Abbreviations: IFI=invasive fungal infection, HSCT=Hematopoietic stem cell transplantation 

2015

abstract No: 

1904

Full conference title: 

ASH 57th Annual Meeting & Exposition
    • ASH 57th (2015)