Jakafi Results in Improved Control of Steroid Refractor/Dependent cGVHD

Among patients with chronic graft-versus-host disease (cGVHD) that was either steroid-refractory or dependent, the condition was better controlled with Jakafi (ruxolitinib) when compared with best available treatment after three years, as demonstrated by longer failure-free survival (when patients don't experience relapse, death or need another treatment) and higher duration of response with the treatment, according to findings from the three-year final analysis of efficacy and safety of the phase 3 REACH3 study.

Findings from this study were presented at the 2023 ASH Meeting and published in the journal Blood.

“(Jakafi) provided longer PFS (progression-free survival, the time a patient lives without their disease worsening) and longer DOR (duration of response) versus (best available treatment), demonstrating sustained efficacy for patients with (steroid-refractory or dependent) cGVHD, with a consistent and manageable safety profile,” Dr. Robert Zeiser, professor in the department of medicine I at the Medical Center at University of Freiburg in Germany, said during a presentation of the data.

Median failure-free survival was longer in the Jakafi group compared with the best available treatment group (38.4 months versus 5.7 months). The probability of failure-free survival at 12 months was 64% in patients assigned Jakafi and 28.8% in those assigned the best available treatment.

Median overall survival (the time a patient lives following treatment, regardless of disease status) was not reached, and no difference was observed in the risk of death in both groups.

The median duration of response was 6.4 months in patients assigned the best available treatment and not reached in those assigned Jakafi. The likeliness of maintaining the duration of response at three years was higher in the Jakafi group versus the best available treatment group.

The rates of non-relapse mortality were similar in the Jakafi (29 of 165) and the best available treatment groups (34 of 164). The rates of malignancy relapse events were similar in both arms for up to three years, occurring in 13 out of 156 patients assigned Jakafi and 11 of 160 patients assigned the best available treatment.

At week 24, the overall response rate (patients whose disease responded partially or completely to treatment) in patients who crossed over from the best available treatment to Jakafi was 50%. This included a complete response in 5.7% of patients and a partial response in 44.3% of patients. Best overall response during the crossover period was 81.4%, with complete response in 7.1% and partial response in 74.3%. Of note, one patient experienced disease progression.

Side Effects

During the main treatment period, almost all patients experienced one or more side effects, affecting 100% of patients assigned Jakafi and 93.7% of patients assigned the best available treatment. Rates of side effects were higher in the Jakafi group vs the best available treatment group. This was likely due to longer follow-up and longer median exposure to Jakafi compared with the best available treatment (52.9 weeks versus 24.1 weeks).

The most common side effect was anemia, with 33.9% in the Jakafi group and 15.8% in the best-available treatment group. Of note, the rate of grade 3 or higher anemia affected the Jakafi group more than the best available treatment group (17.6% versus 9.5%). Rates of grade 3 or worse thrombocytopenia, neutropenia, gamma-glutamyltransferase increase and alanine aminotransferase increase were 5% higher in patients assigned Jakafi compared with the best available treatment.

The most common treatment-related side effects in the Jakafi group were anemia, which occurred in 24.2% of patients. Grade 3 or higher anemia also occurred in 10.3% of patients in this group. For patients assigned the best available treatment, the most common treatment-related side effect was thrombocytopenia (3.8%).

Infections, not including tuberculosis, were the most common side effects of special interest in the Jakafi and best-available treatment groups (77.6% versus 68.4%, respectively). Grade 3 or higher infections occurred in 31.5% of patients assigned Jakafi and 26.6% of those assigned to the best available treatment.

Most deaths that occurred while on treatment were due to cGVHD, occurring in 10 of 18 patients assigned Jakafi and in six of 12 patients assigned to the best available treatment.

Study Design

Patients aged 12 years and older with moderate or severe steroid-refractory cGVHD were randomized evenly to receive either 10 mg of Jakafi twice daily (165 patients) or the best available treatment (164 patients), as selected by the investigator. All patients were followed for three years, until discontinuation or death.

The primary analysis of the study, which was conducted at week 24 (cycle 7, day 1) in all patients randomized to treatment, then patients entered an extension period from cycles 7 to 39, during which treatment continued, patients switched from the best available treatment to Jakafi (crossover cohort) or discontinued treatment. Patients who discontinued treatment entered long-term survival follow-up.

At three years, researchers analyzed several outcomes including failure-free survival, duration of response, non-relapse mortality, overall survival, safety and malignancy relapse. The final data cutoff was Dec. 15, 2022.

In addition, other outcomes were assessed during the crossover treatment period — patients who switched from the best available treatment to Jakafi on or after cycle 7, day 1 — including overall response rate and best overall response.

Of the 329 patients who were randomized to treatment, 53 patients completed the treatment period and 276 patients discontinued. In addition, 115 patients entered survival follow-up, with 73 out of 165 patients from the Jakafi group and 42 out of 164 in the best available treatment group. Seventy patients crossed over from the best available treatment to Jakafi, of whom 16 completed the crossover treatment period and 24 patients entered survival follow-up.

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