Loading...
Allogeneic stem cell transplantation (allo SCT) is a curative option for patients with high-grade hematologic malignancy. However, the procedure may be complicated by acute or chronic graft-versus-host disease (GVHD), the treatment for which includes increasing immunosuppressive therapy.
Now, investigators have conducted an industry-funded, multicenter, randomized, open-label phase III trial of the oral Janus kinase (JAK) inhibitor ruxolitinib versus investigator's choice of treatment from among nine other options in 309 patients (age, ≥12 years) who had undergone allo SCT and had grade II–IV glucocorticoid-refractory acute GVHD.
The overall response rate (ORR) at day 28 (the primary end point) was higher with ruxolitinib than with investigator's choice of treatment (62% vs. 39%; P<0.001). ORR at day 56 was also improved with ruxolitinib (40% vs. 22%; P<0.001), as was maintenance of response at 6 months (90% vs. 61%). Ruxolitinib recipients had a higher rate of any grade thrombocytopenia through day 28 (33% vs. 18%) and a marginally higher rate of any grade cytomegalovirus infection (26% vs. 21%).
Zeiser R et al. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. N Engl J Med 2020 Apr 22; [e-pub]. (https://doi.org/10.1056/NEJMoa1917635)
Comment
The availability of alternative donor cell types, including cord blood and haploidentical SCT, has allowed greater numbers of patients to undergo allo SCT, albeit with success tempered by risk for GVHD and its impact on quality of life and mortality when glucocorticoid-refractory. The efficacy and generally favorable toxicity profile of ruxolitinib and the recent approval of the Bruton tyrosine kinase inhibitor ibrutinib for GVHD are welcome advances to improve outcomes following allo SCT.