The Community Focus Channel is supported with funding from Johnson & Johnson (Gold).
VJHemOnc is an independent medical education platform. Supporters, including channel supporters, have no influence over the production of content. The levels of sponsorship listed are reflective of the amount of funding given to support the channel.
EBMT 2026 | The real-world efficacy and toxicity profile of ruxolitinib in pediatric acute and chronic GvHD
Andrea Buonsante, MD, University of Milano-Bicocca, Monza, Italy, presents the results of a multicenter retrospective study investigating the real-world efficacy and toxicity profile of ruxolitinib in pediatric patients with acute and chronic graft-versus-host disease (GvHD). Dr Buonsante highlights the encouraging efficacy in this patient population, but notes that the lower complete response (CR) rates observed in children below 12 years of age warrant further investigation. Consistent with recent prospective trials, the findings of this analysis support earlier initiation of ruxolitinib during the GvHD treatment course, as patients with more severe and heavily pretreated disease demonstrated poorer outcomes. This interview took place at the 52nd Annual Meeting of the EBMT in Madrid, Spain.
These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.
Transcript
Graft-versus-host disease is a major cause of morbidity and mortality in pediatric patients and although systemic corticosteroids represent the first line therapy in these patients, up to half of them actually become steroid refractory or steroid resistant, therefore necessitating a new immunosuppressive agent line. Several different drugs have been tested on the pediatric population, mainly starting from studies in the adults, but often leading to non-durable responses...
Graft-versus-host disease is a major cause of morbidity and mortality in pediatric patients and although systemic corticosteroids represent the first line therapy in these patients, up to half of them actually become steroid refractory or steroid resistant, therefore necessitating a new immunosuppressive agent line. Several different drugs have been tested on the pediatric population, mainly starting from studies in the adults, but often leading to non-durable responses. Ruxolitinib is a JAK1/2 inhibitor that has been tested in the pediatric population with promising results. Based on prospective trials, it is currently the only drug approved for the treatment of GVHD with inadequate response to steroids in patients older than 12 years old. Recently, REACH4 and REACH5 trials have also extended these findings in patients younger than 12 years old.
Recently, REACH 4 and REACH 5 trials have also extended these findings in patients younger than 12 years old with promising results. And that’s why we decided to retrospectively collect data from 55 GVHD treatment episodes in three different transplantation Italian centers. In particular, there were 32 acute GVHD and 23 overlap chronic GVHD cases and the overall response rates were respectively 75 and 78 percent consistently with the recent literature and then we moved to investigate potential predictors of response. In acute GVHD, patients with gastrointestinal involvement had lower response rates, as only 57% of them responded to the therapy, while 100% of patients with only skin involvement responded to therapy. And the response was also associated with a higher total nucleated cell dose-infused transplant as it was correlated with a lower overall response rates, probably due to some biological explanation because actually the TNC dose was not associated with the GVHD severity. And so that could be associated with, for example, a higher immune burden from the donor and potentially a direct cytotoxic effect of T-cells. Importantly, patients within 6 and 12 years old had lower complete response rates than the rest of the age groups, only 20%. While in chronic GVHD, there was no association with age or GVHD severity, but patients who received more than two prior lines of immunosuppressive therapy had lower response rates. Actually, only half of them responded to therapy, while over 90% of patients receiving two or less prior lines responded to ruxolitinib.
Treatment failure was defined as the initiation of a new immunosuppressive agent during ruxolitinib therapy and patients with grade 3, 4 acute GVHD actually had a cumulative incidence of failure over 50% at six months while it was only 20% in lower grades and chronic GVHD and importantly, patients with less than 12 years old had a cumulative incidence of failure of 35% at six months, while over 12 years old, it was only 11%. Finally, toxicity was consistent with recent literature studies. 36% of patients suspended therapy due to toxicity, but it was often multifactorial.
So we could say that we have three key take-home messages from our study. The first one, we confirmed the high efficacy and safety profile of ruxolitinib in the pediatric population, even though patients younger than 12 years old need further investigation in larger studies, in particular investigating, for example, the response, the durability of response, and the rate of treatment failure. Then, the worst outcomes in our studies were associated with GVHD severity, organ involvement, and the prior lines of immunosuppressive agents, meaning that patients with more severe disease and more heavily pretreated had lower outcomes, and this support the rationale for an earlier initiation of ruxolitinib during the GVHD treatment course, consistently with the recent prospective trials in the pediatric populations. And finally, our findings on the potential predictor of response may be further studied in the future larger studies as they could help optimize the treatment strategies of these patients.
This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.
Read more...
