As reported in the Journal of Clinical Oncology by Miklos et al, the phase III iNTEGRATE trial showed no benefit of the addition of ibrutinib to prednisone in the first-line treatment of moderate or severe chronic graft-vs-host disease (GVHD) after allogeneic hematopoietic cell transplantation.
Study Details
In the international double-blind trial, 193 patients aged ≥ 12 years requiring systemic corticosteroid therapy were randomly assigned to receive ibrutinib at 420 mg (n = 98) or placebo (n = 95) once daily, with both groups starting prednisone at 1 mg/kg once daily; ibrutinib and placebo were given until chronic GVHD progression, relapse of underlying malignancy, initiation of another systemic chronic GVHD treatment, or unacceptable toxicity. The primary endpoint was response rate at 48 weeks according to 2014 National Institutes of Health Consensus Development Project Criteria.
Key Findings
At final analysis, median follow-up was 33 months (range = 0.03–47.20 months). At 48 weeks, response rates were 41% with ibrutinib/prednisone vs 37% with placebo/prednisone (P = .54). Follow-up at 96 weeks showed response rates of 27% vs 22% (P = .43).
The median duration of response was 19 months (95% confidence interval [CI] = 7 months to not evaluable) vs 10 months (95% CI = 6.5–17 months, P = .10), with 24-month duration of response estimates of 45% vs 32%. Median event-free survival was 15 months (95% CI = 6–27 months) vs 8 months (95% CI = 6–13 months), with a hazard ratio of 0.76 (95% CI = 0.54–1.07, P = .11).
Proportions of patients with improvement via the overall Lee chronic GVHD Symptom Scale were 43% vs 31% (P = .07). Estimated 24-month overall survival rates were 80% vs 80% (HR = 1.06, 95% CI = 0.59–1.90). Grade ≥ 3 adverse events occurred in 68% vs 67% of patients; grade ≥ 3 serious adverse events occurred in 49% vs 47%.
The investigators concluded, “There was no statistical difference observed in the primary and secondary endpoints with ibrutinib/prednisone treatment. No new safety signals were observed with ibrutinib treatment in previously untreated patients with chronic GVHD. The primary end point of iNTEGRATE was not met.”
David Bernard Miklos, MD, PhD, of Stanford University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Pharmacyclics LLC, an AbbVie Company. For full disclosures of the study authors, visit ascopubs.org.
