FDA Approves Ruxolitinib for Chronic GVHD


The FDA has approved ruxolitinib for the treatment of chronic graft-versus-host disease following failure of 1 or 2 lines of systemic therapy in adult and pediatric patients aged 12 years and older.



The FDA has approved ruxolitinib (Jakafi) for the treatment of chronic graft-versus-host disease (GVHD) following failure of 1 or 2 lines of systemic therapy in adult and pediatric patients aged 12 years and older.1

The regulatory decision was supported by findings from the phase 3 REACH3 trial (NCT03112603), which demonstrated that ruxolitinib elicited an overall response rate (ORR) of 49.7% at week 24 vs 25.6% with best available therapy (BAT; odds ratio, 2.99; P < .0001).2 The ORR through cycle 7 day 1 was 70% in the investigative arm vs 57% in the control arm.3 Notably, a higher overall response was observed with ruxolitinib vs BAT irrespective of the organs involved.

“GVHD is the leading cause of morbidity and mortality in patients following an allogeneic stem cell transplant, yet there historically have been limited treatment options available beyond first-line systemic therapies,” Steven Stein, MD, chief medical officer of Incyte, stated in a press release. “Incyte is proud to have contributed to the overall scientific understanding of GVHD through our REACH program, which has led to important treatment advances on behalf of patients and the medical community, including today’s approval of [ruxolitinib] for certain people who develop chronic GVHD."

The open-label, multicenter, phase 3 trial enrolled patients who were at least 12 years of age who had undergone allogeneic stem cell transplantation and had moderate or severe glucocorticoid-refractory or -dependent chronic GVHD.

A total of 329 participants were randomized 1:1 to receive either ruxolitinib at a twice-daily dose of 10 mg (n = 165) or investigator's choice of therapy (n = 164), which could include any of the following options: extracorporeal photopheresis, low-dose methotrexate, mycophenolate mofetil, everolimus (Afinitor) or sirolimus (Rapamune), infliximab (Remicade), rituximab (Rituxan), pentostatin, imatinib (Gleevec), or ibrutinib (Imbruvica). Treatment was given for at least 6 cycles, unless intolerable toxicity or progression was experienced.

Patients continued to receive glucocorticoids with or without calcineurin inhibitors. Notably, infection prophylaxis was allowed and given in accordance with local institutional guidelines.

The primary end point of the trial was ORR at week 24, and important secondary end points comprised failure-free survival (FFS) and response on the modified Lee Symptom Scale at week 24. Other end points included subgroup analyses of overall response, individual organ responses, best overall response at any time up to week 24, duration of response, change in glucocorticoid dose over time, overall survival (OS), and changes in quality-of-life measures.

Patient characteristics were reported to be balanced between the 2 treatment arms. The median age of patients was 49 years (range, 12-76), with 12 patients between the ages of 12 and 17 years. More than half of patients, or 61.1%, were male. Moreover, 42.9% of patients had moderate chronic GVHD, 56.5% had severe chronic GVHD, 71.4% had glucocorticoid-refractory chronic GVHD, and 28.6% had glucocorticoid-dependent disease per investigator assessment.

Within the control arm, 34.8% of patients received extracorporeal photopheresis, 22.2% received mycophenolate mofetil, and 17.1% received ibrutinib. About half of the patients received calcineurin inhibitors throughout the trial duration.

At a median follow-up of 57.3 weeks, and a data cutoff of May 8, 2020, 38.0% of patients continued to receive the treatment they were assigned to. Moreover, 49.7% of patients discontinued ruxolitinib and 74.4% discontinued their control therapy. The reasons for treatment discontinuation with ruxolitinib or control therapy, respectively, included lack of efficacy (14.5% vs 42.7%), toxicities (17.0% vs 4.9%), and relapse of underlying disease (5.5% vs 4.3%).

A total 37.2% of patients on the control arm crossed over to receive treatment on the investigative arm.

Additional data from the trial, which were published in the New England Journal of Medicine, showed that those who received ruxolitinib also experienced a longer FFS, with a median FFS of longer than 18.6 months vs 5.7 months, respectively (HR, 0.37; 95% CI, 0.27-0.51; P < .001). Although the median FFS was not reached in the investigative arm, the lower boundary of the 95% CI was estimated as 18.6 months, with the efficacy boundary crossed at the time of the interim analysis.

Moreover, the probability of FFS at 6 months was also estimated to be higher with ruxolitinib vs the control therapy, at 74.9% (95% CI, 67.5%-80.9%) vs 44.5% (95% CI, 36.5%-52.1%), respectively.

Although the dose of glucocorticoids was noted to decrease in both arms, the decrease was slightly greater with ruxolitinib.

In the ruxolitinib arm, a best overall response rate up to week 24 was noted in 76.4% of patients; this rate was 60.4% in the control arm (odds ratio, 2.17; 95% CI, 1.34-3.52; risk ratio, 1.24; 95% CI, 1.07-1.43; P = .001). In those who experienced a response to treatment at any time, the estimated probability of maintaining a response at 1 year was higher with ruxolitinib vs control therapy, at 68.5% (95% CI, 58.9%-76.3%) and 40.3% (95% CI, 30.3%-50.2%), respectively.

The OS data were still immature at the time of the data cutoff. The median OS had not yet been reached in either arm (HR, 1.09; 95% CI, 0.65-1.82). The estimated 12-month OS rates in the investigative and control arms were 81.4% (95% CI, 74.1%-86.8%) and 83.8% (95% CI, 76.5%-89.0%).

A total of 323 patients were included in the safety analyses of the trial; 165 were on the investigative arm and 158 were in the control arm. To be included, patients must have received at least 1 dose of trial therapy up to week 24.

Any-grade adverse effects (AEs) up to week 24 were experienced by 97.6% of those on ruxolitinib vs 91.8% of those on control therapy. Grade 3 or higher AEs were reported in 57.0% and 57.6% of patients, respectively.

The most common grade 3 or higher toxicities on the investigative and control arms, respectively, included thrombocytopenia (15.2% vs 10.1%), anemia (12.7% vs 7.6%), neutropenia (8.5% vs 3.8%), and pneumonia (8.5% vs 9.5%). Infections were reported in 63.6% of those given ruxolitinib vs 56.3% of those given control therapy.

Serious AEs up to week 24 were reported in 33.3% of those who received ruxolitinib vs 36.7% of those who were given the control therapy.

Moreover, 16.4% and 7.0% of patients on the investigative and control arms, respectively, experienced toxicities that resulted in treatment discontinuation. Dose interruptions occurred in 37.6% vs 16.5% of patients, respectively. Thirty-one patients on the investigative arm died vs 27 patients on the control arm. Deaths were primarily because of complications caused by chronic GVHD or treatment.

“Nearly half of the people who develop chronic GVHD do not respond adequately to steroids – the current standard of care – making this life-threatening condition particularly challenging to treat,” Robert Zeiser, MD, University Medical Center Freiburg, Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg, Germany, and the principal investigator of REACH3, stated in a press release. “In this clinical trial, treatment with Jakafi demonstrated significantly improved outcomes across a range of efficacy measures compared to best available therapy. This approval represents a significant advancement in the treatment of appropriate patients with chronic GVHD – for both the patients who face a poor prognosis and the healthcare providers who struggle to effectively treat them.”


  1. Incyte announces FDA approval of Jakafi (ruxolitinib) for treatment of chronic graft-versus-host disease (GVHD). News release. Incyte. September 22, 2021. Accessed September 22, 2021. https://bwnews.pr/3m5XRTJ
  2. Zeiser R, Polverelli N, Ram R, et al. Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease. N Engl J Med. 2021;385(3):228-238. doi:10.1056/NEJMoa2033122
  3. Jakafi (ruxolitinib) tables: Prescribing information. FDA. September 2021. Accessed September 22, 2021. https://bit.ly/39tTZpw
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