TY - JOUR
T1 - Fluticasone, Azithromycin, and Montelukast Treatment for New-Onset Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation
AU - Williams, Kirsten M.
AU - Cheng, Guang Shing
AU - Pusic, Iskra
AU - Jagasia, Madan
AU - Burns, Linda
AU - Ho, Vincent T.
AU - Pidala, Joseph
AU - Palmer, Jeanne
AU - Johnston, Laura
AU - Mayer, Sebastian
AU - Chien, Jason W.
AU - Jacobsohn, David A.
AU - Pavletic, Steven Z.
AU - Martin, Paul J.
AU - Storer, Barry E.
AU - Inamoto, Yoshihiro
AU - Chai, Xiaoyu
AU - Flowers, Mary E.D.
AU - Lee, Stephanie J.
N1 - Publisher Copyright:
© 2016 American Society for Blood and Marrow Transplantation.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT) is associated with high mortality. We hypothesized that inhaled fluticasone, azithromycin, and montelukast (FAM) with a brief steroid pulse could avert progression of new-onset BOS. We tested this in a phase II, single-arm, open-label, multicenter study (NCT01307462). Thirty-six patients were enrolled within 6 months of BOS diagnosis. The primary endpoint was treatment failure, defined as 10% or greater forced expiratory volume in 1 second decline at 3 months. At 3 months, 6% (2 of 36, 95% confidence interval, 1% to 19%) had treatment failure (versus 40% in historical controls, P <.001). FAM was well tolerated. Steroid dose was reduced by 50% or more at 3 months in 48% of patients who could be evaluated (n = 27). Patient-reported outcomes at 3 months were statistically significantly improved for Short-Form 36 social functioning score and mental component score, Functional Assessment of Cancer Therapies emotional well-being, and Lee symptom scores in lung, skin, mouth, and the overall summary score compared to enrollment (n = 24). At 6 months, 36% had treatment failure (95% confidence interval, 21% to 54%, n = 13 of 36, with 6 documented failures, 7 missing pulmonary function tests). Overall survival was 97% (95% confidence interval, 84% to 100%) at 6 months. These data suggest that FAM was well tolerated and that treatment with FAM and steroid pulse may halt pulmonary decline in new-onset BOS in the majority of patients and permit reductions in systemic steroid exposure, which collectively may improve quality of life. However, additional treatments are needed for progressive BOS despite FAM.
AB - Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT) is associated with high mortality. We hypothesized that inhaled fluticasone, azithromycin, and montelukast (FAM) with a brief steroid pulse could avert progression of new-onset BOS. We tested this in a phase II, single-arm, open-label, multicenter study (NCT01307462). Thirty-six patients were enrolled within 6 months of BOS diagnosis. The primary endpoint was treatment failure, defined as 10% or greater forced expiratory volume in 1 second decline at 3 months. At 3 months, 6% (2 of 36, 95% confidence interval, 1% to 19%) had treatment failure (versus 40% in historical controls, P <.001). FAM was well tolerated. Steroid dose was reduced by 50% or more at 3 months in 48% of patients who could be evaluated (n = 27). Patient-reported outcomes at 3 months were statistically significantly improved for Short-Form 36 social functioning score and mental component score, Functional Assessment of Cancer Therapies emotional well-being, and Lee symptom scores in lung, skin, mouth, and the overall summary score compared to enrollment (n = 24). At 6 months, 36% had treatment failure (95% confidence interval, 21% to 54%, n = 13 of 36, with 6 documented failures, 7 missing pulmonary function tests). Overall survival was 97% (95% confidence interval, 84% to 100%) at 6 months. These data suggest that FAM was well tolerated and that treatment with FAM and steroid pulse may halt pulmonary decline in new-onset BOS in the majority of patients and permit reductions in systemic steroid exposure, which collectively may improve quality of life. However, additional treatments are needed for progressive BOS despite FAM.
KW - Azithromycin
KW - Bronchiolitis obliterans syndrome
KW - Fluticasone
KW - Hematopoietic cell transplantation
KW - Leukotrienes
KW - Lung chronic graft-versus-host disease
KW - Montelukast
UR - http://www.scopus.com/inward/record.url?scp=84960473094&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2015.10.009
DO - 10.1016/j.bbmt.2015.10.009
M3 - Article
C2 - 26475726
AN - SCOPUS:84960473094
SN - 1083-8791
VL - 22
SP - 710
EP - 716
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 4
ER -