By Lynda Williams, medwireNews Reporter
medwireNews: Combining ibrutinib and prednisone for the treatment of new-onset chronic graft-versus-host disease (cGVHD) after allogeneic haematopoietic cell transplantation does not improve patient response compared with prednisone alone, show phase 3 trial findings published in the Journal of Clinical Oncology.
“There was no statistical difference observed in the primary and secondary endpoints with ibrutinib–prednisone treatment”, say the iNTEGRATE study investigators, led by David Miklos from Stanford University in California, USA.
The trial was designed to overcome the morbidity associated with corticosteroid therapy and follows the US approval of ibrutinib for the treatment of cGVHD after one or more failed lines of systemic therapy, they explain.
Patients aged 12 years and older (median age 51–56 years) with a new diagnosis of moderate or severe cGVHD a median of 8 months after transplantation were randomly assigned to receive ibrutinib 420 mg/day plus prednisone beginning at a 1 mg/kg daily dose or placebo plus prednisone.
Treatment lasted for a median of 5 months and 6 months in the two treatment arms, respectively, with both groups receiving a median total prednisone dose of 4 g.
The 48-week primary endpoint of a complete response or a partial response – defined as an improvement in at least one organ or site without progression in other organs or sites – was achieved by a comparable 41% of the 95 patients given ibrutinib–prednisone and 37% of the 98 controls.
An improvement in the overall Lee cGVHD Symptom Scale score of at least 7 points occurred on at least two consecutive visits in 43% of patients given ibrutinib–prednisone and 31% of controls.
After a median follow-up of 33 months, the median duration of response in the ibrutinib–prednisone and placebo–prednisone arms was 19 and 10 months, respectively, and the corresponding rates of median event-free survival were 15 months and 8 months. The estimated 24-month overall survival rate was 80% for both trial arms, Miklos et al report.
Grade 3 and more severe treatment-emergent adverse events (AEs) occurred in 68% of patients given ibrutinib–prednisone and 67% of those given placebo–prednisone, most commonly insomnia (28 vs 19%), peripheral oedema (27 vs 15%) and cough (21 vs 30%). Serious AEs occurred in 52% and 49% of the study arms, respectively, with 28% and 27% attributed to prednisone.
Of note, there was a higher rate of fatal AEs with ibrutinib than placebo (13 vs 6%) but the researchers emphasize that the rates of AEs of special interest, such as infection, hypertension, atrial fibrillation and cardiac arrest, were comparable.
Recognising that there were “positive trends” in the ibrutinib–prednisone arm for some endpoints, Miklos and team suggest that a “[a] head-to-head trial comparing ibrutinib with prednisone could elucidate beneficial effects of ibrutinib as a single agent in the treatment of cGVHD, potentially reducing the toxic effects of corticosteroids.”
They conclude that “future studies may elucidate the clinical and laboratory markers that predict response to therapy, and the impacts of timing and/or therapeutic combinations on efficacy and safety outcomes.”
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J Clin Oncol 2023; doi.10.1200/JCO.22.00509