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

Yi-Bin Chen, Miguel-Angel Perales, Shuli Li, Maria Kempner, Carol Reynolds, Jami Brown, Yvonne A. Efebera, Steven M. Devine, Areej El-Jawahri, Steven L. McAfee, Thomas R. Spitzer, Robert J. Soiffer, Jerome Ritz and Corey Cutler

Key Points

  • BV has activity for SR-aGVHD.

  • The MTD of BV was 0.8 mg/kg every 2 weeks for 4 doses.


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 aGVHD. 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. This trial was registered at as #NCT01940796.

  • Submitted March 7, 2017.
  • Accepted April 29, 2017.
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