According to research published in Blood, ruxolitinib monotherapy may be an effective treatment option with good tolerance in children with hemophagocytic lymphohistiocytosis (HLH), providing clinical evidence for ruxolitinib as a frontline agent in pediatric HLH.

“[HLH] is a lethal disorder characterized by hyperinflammation. Recently, [ruxolitinib], targeting key cytokines in HLH, has shown promise for HLH treatment. However, there is a lack of robust clinical trials evaluating its efficacy, especially its utility as a frontline therapy,” the researchers wrote in their report.  

The researchers evaluated the safety and efficacy of ruxolitinib as a first-line agent for pediatric HLH. Patients were stratified based on early response to frontline ruxolitinib (up to 28 days); those with favorable response remained on ruxolitinib monotherapy for 4 weeks and those with unfavorable response received response-adapted intensive treatment with a combination of ruxolitinib plus chemotherapy for 8 weeks (Chinese Clinical Trials Registry Platform: ChiCTR2000031702).

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The primary endpoint was the overall response rate (ORR) at the end of frontline ruxolitinib monotherapy, and secondary endpoints included safety, the proportion of patients achieving complete response (CR) after treatment overall and 12-month overall survival (OS).

A total of 52 newly diagnosed patients, with a median age of 3.7 years (range, 0.1-14.4) participated in the study. Most patients (65.4%) had received no prior corticosteroid treatment, while 34.6% of patients were receiving corticosteroids at the time of screening. A favorable and unfavorable response was observed in 42% and 58% of patients respectively. The median follow-up duration was 11.2 months (range, 0.72-17.54), and at data cutoff, 82.7% of patients were alive. The median time to additional treatment from the first ruxolitinib administration was 6 days (range, 3-25).

Patients treated with ruxolitinib monotherapy had an ORR of 69.2%, with 42.3% achieving CR. All patients who responded to the treatment achieved their first response to ruxolitinib within 3 days. The researchers also demonstrated that response to ruxolitinib was significantly associated with disease etiology at enrollment (P =.009) and patients with Epstein-Barr virus (EBV)-HLH were most sensitive to ruxolitinib, with an ORR of 87.5% (CR, 58.3%).

After frontline ruxolitinib therapy, the 58% of patients with unfavorable response received the combination of ruxolitinib plus additional chemotherapy for 8 weeks. Of those, 53.3% achieved CR. The researchers found that 47% patients had chronic active EBV infection-associated HLH and developed refractory HLH by week 8.

Overall, 73% of patients achieved CR after treatment, and the 12-month OS was 86% (95% CI, 77%-96%).

“In summary, our study demonstrates that [ruxolitinib] is an effective treatment option with good tolerance for pediatric HLH patients,” concluded the authors. “The study provides support for the use of [ruxolitinib] as a frontline agent and stratification of patients based on early [ruxolitinib] response for subsequent therapy.”

Limitations of the study included the dosage-related efficacy of ruxolitinib, limited therapeutic window in HLH (higher doses may be required in patients with unfavorable response to ruxolitinib monotherapy), an imbalance in the number of different underlying etiologies among the patients, and exclusion of patients who were critically ill and those with severe CNS involvement.


Zhang Q, Zhao YZ, Ma HH, et al. A study of ruxolitinib response-based stratified treatment for pediatric hemophagocytic lymphohistiocytosis. Blood. 2022;139(24):3493-3504. doi:10.1182/blood.2021014860