TCT 2019—Ibrutinib shows potential for second-line therapy for pediatric cGVHD


  • Tara Haelle
  • Univadis
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Takeaway

  • Partial response to ibrutinib for chronic graft vs host disease (cGVHD) in pediatric hematopoietic cell transplantation (HCT) recipients suggests its use as salvage therapy.

Why this matters

  • cGVHD is a leading cause of late nonrelapse mortality after HCT.
  • No second-line treatment for children exists after steroids, which have high toxicity with long-term use.

Study design

  • Retrospective review of ibrutinib use for cGVHD at Cincinnati Children’s Hospital Medical Center: 12 patients (median, 11 years; range, 3-19 years) with cGVHD (8 severe, 1 moderate, 3 mild) received 250 mg/m2 orally once daily from August 2017 to October 2018.
    • Patients had steroid-dependent (n=2) or -refractory (n=10) cGVHD.
    • Dose halved for concomitant CYP3A4 inhibitor.
    • Median dose 140 mg (70-420 mg).
    • Median duration 170.5 days (28-341 days).
  • Diagnoses: malignancy (46%), primary immune deficiency (15%), and hemoglobinopathies (30%).
  • Stem cell sources: bone marrow (59%), cord blood (16%), and peripheral blood (25%). 

Key results

  • 8 of 8 evaluable patients at 6 months achieved partial response; 4 discontinued (death/adverse events).
  • Of 6 patients with lung involvement, 1 recovered lung function, 1 improved, and 2 were stable. 
  • 1 patient discontinued steroids, 2 weaned to physiologic steroids, and 5 weaned to 50% of pre-ibrutinib dose. 
  • Following ibrutinib initiation, levels of plasma IL-6 (n=7) and CXCL9 (n=5) declined. 
  • Adverse events: 3 thrombocytopenia, 2 neutropenia, 1 pneumococcal sepsis, 1 Epstein-Barr virus activation.

 

Highlights from TCT Meetings 2019