Phase 1 multicenter trial of brentuximab vedotin for steroid-refractory acute graft-versus-host disease Journal Article


Authors: Chen, Y. B.; Perales, M. A.; Li, S.; Kempner, M.; Reynolds, C.; Brown, J.; Efebera, Y. A.; Devine, S. M.; El-Jawahri, A.; McAfee, S. L.; Spitzer, T. R.; Soiffer, R. J.; Ritz, J.; Cutler, C.
Article Title: Phase 1 multicenter trial of brentuximab vedotin for steroid-refractory acute graft-versus-host disease
Abstract: Therapy for steroid-refractory acute graft-versus-host disease (SR-aGVHD) remains suboptimal. Preclinical data demonstrate increased CD30 expression on activated CD8+ T cells during a GVHD. Brentuximab vedotin (BV) is an antibody-drug conjugate targeting CD30. We conducted a multicenter phase 1 trial in 34 patients to establish the maximum tolerated dose (MTD) of BV for SR-aGVHD treatment. A 3+3 cohort design was conducted initially with BV given weekly × 3 doses followed by maintenance dosing (initial dose 0.6 mg/kg IV weekly). Six patients were treated with the initial weekly dosing scheme; 2 of these patients died of neutropenic sepsis complications. The trial was subsequently revised to escalating cohorts of 5 patients treated every 2 weeks × 4 doses with a 4-week dose-limiting toxicity (DLT) period. Twenty-eight patients were treated with every-2-week dosing (n = 10 at 0.6 mg/kg; n = 18 at 0.8 mg/kg). MTD was defined at 0.8 mg/kg with 1 DLT observed (sepsis). At day 28, the overall response rate was 38.2% with 5 complete responses (CRs; 14.7%) and 8 very-good-partial responses (23.5%). An additional 7 patients achieved CR by day 56. With 12 months' follow-up on all patients, overall survival was 41% (95% confidence interval [CI], 25%-57%) at 6 months and 38% (95% CI, 22%-54%) at 12 months. CD30 expression on central memory CD8+, central memory CD4+, and regulatory T-lymphocyte subsets at enrollment was not associated with clinical response. BV is tolerable and has activity in SR-aGVHD and merits further investigation. © 2017 by The American Society of Hematology.
Journal Title: Blood
Volume: 129
Issue: 24
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2017-06-15
Start Page: 3256
End Page: 3261
Language: English
DOI: 10.1182/blood-2017-03-772210
PROVIDER: scopus
PUBMED: 28473406
DOI/URL:
Notes: Article -- Export Date: 2 August 2017 -- Source: Scopus
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MSK Authors
  1. Miguel-Angel Perales
    354 Perales