Ibrutinib plus prednisone did not improve outcomes among patients with previously untreated chronic graft vs host disease (cGVHD), according to the results of the phase 3 INTEGRATE study published in the Journal of Clinical Oncology.
Ibrutinib is currently approved by the US Food and Drug Administration for the treatment of cGVHD that has been previously treated with 1 or more systemic therapies. The aim of this study was to determine if ibrutinib could improve outcomes in the frontline setting of cGVHD.
The double-blind, phase 3 INTEGRATE trial randomly assigned 193 patients aged 12 or older with moderate to severe and previously untreated cGVHD to receive ibrutinib plus prednisone or placebo plus prednisone. The primary endpoint was response rate at 48 weeks and secondary endpoints included event-free survival (EFS), improvement in overall Lee cGVHD Symptom Scale, and overall survival (OS). The median follow-up was 33 months.
At baseline, the median age was 54 (range, 13-76), 65% of patients were male, and 54% were White. There were 53% of patients who received a myoablative transplant, and the majority of patients received stem cells from a peripheral stem cell source. The median time for transplant to cGVHD was 8 months and 43% of patients had severe disease.
Ibrutinib plus prednisone failed to meet the primary endpoint. The response rates in the ibrutinib and placebo groups were similar at 48 weeks, at 41% and 37%, respectively (P =.54). The duration of response with 19 months with ibrutinib and 10 months with placebo (P =.10).
EFS was also similar between the groups, with a median of 15 months with ibrutinib compared with 8 months with placebo (hazard ratio [HR], 0.76; 95% CI, 0.54-1.1; P =.11). The median OS was not yet reached, but the 24-month OS was 80% in the ibrutinib and placebo groups (HR, 1.06; 95% CI, 0.59-1.90).
There was no significant difference in the improvement in the overall Lee cGVHD Symptom Scale at 43% and 31% in the ibrutinib and placebo groups, respectively (P =.07).
There were 49% of patients in the ibrutinib arm and 47% in the placebo arm who developed grade 3 or higher serious adverse events. Of these, 28% and 27% in the ibrutinib and placebo arms, respectively, were considered related to corticosteroids.
The authors concluded that “there was no statistical difference observed in the primary or secondary endpoints with ibrutinib-prednisone treatment.”
Disclosures: This study was supported by Pharmacyclics, LLC, an AbbVie Company. Please see the original reference for a full list of disclosures.
Miklos DB, Zaid MA, Cooney JP, et al. Ibrutinib for first-line treatment of chronic graft-versus-host disease: results from the randomized phase III iNTEGRATE study. J Clin Oncol. Published online January 6, 2023. doi: 10.1200/JCO.22.00509