Patients with myelofibrosis (MF) who achieved a spleen response while taking ruxolitinib and lost it had survival outcomes similar to patients who did not respond, according to results from a real-world study.
Patients with myelofibrosis (MF) have a significant rate of infections when prescribed ruxolitinib (Jakafi), but those who achieved spleen responses had better overall outcomes, according to a new study based on real-world usage.
The authors of the report, which was published in Cancer Medicine, say the findings provide important insights into the therapy’s safety and efficacy outside of a trial setting.
Corresponding author Alessandro M. Vannucchi, MD, of Italy’s University of Florence, and colleagues, said ruxolitinib performed well in clinical trials, achieving clinically meaningful and durable responses, including a reduction in splenomegaly and disease-related symptoms, and increased quality of life. Yet, they said, there is a need for more real-world evidence to show how ruxolitinib has performed in patients with MF since the therapy became commercially available.
The authors decided to retrospectively analyze the outcomes of patients who were treated at 7 Italian tertiary centers who either began using ruxolitinib commercially between January 2015 and March 2018 or who were enrolled in the JUMP trial and continued using the therapy following the trial’s end in September 2014. The participating centers are part of the Myeloid Neoplasms Research Venture (MYNERVA) Project.
A total of 154 patients were included in the study, and they had a median drug exposure of 29 months. About 1 in 4 patients discontinued therapy (27%) after a median time of 13 months. The most common reason people discontinued therapy was hematopoietic stem cell transplantation (24%). The other reasons patients discontinued were infection, loss of response, progressive disease, and death (12% for each reason).
“While hematological toxicities were in line with previous findings, infections occurred frequently, representing a not negligible cause of discontinuation and death,” Vannucchi and colleagues wrote.
Ninety-one percent of patients achieved improvement in their symptoms at any time during treatment, and 68% of patients reported spleen responses. Twenty-three percent of patients had anemia responses. In most cases, the authors said, responses were achieved by week 24. Patients with larger splenomegaly and delayed treatment initiation were less likely to have spleen responses at week 24.
The investigators noted that their rate of palpable spleen response was higher than in the COMFORT trials of ruxolitinib. They added, however, that later trials and existing real-world evidence had rates more consistent with the current report.
After a median follow-up time of 33 weeks, 18 patients had died and 7 patients had experienced leukemic transformation. Those who achieved spleen responses had superior overall survival hazard ratio [HR] 3.6; 95% CR, 1.2–10.8, P = .0163). That survival advantage held true even when adjusted for dynamic international scoring system (DIPSS) risk scores.
“We then assessed the impact of [spleen response] loss, and found that OS of patients who lost their [spleen response] was significantly worse compared to patients who maintained the response (HR 9.7, 95% CI 1.2–82.6, p = 0.0004), and not significantly different in comparison to non-responders (p = 0.2),” the authors wrote.
The authors noted limitations to their research, including the retrospective design and small patient cohort. However, they said their findings offer important insights into the risk of infections and the impressive symptomatic reductions seen in patients with MF who take ruxolitinib, as well as the importance of spleen response—or lack thereof—in overall patient outcomes.
Coltro G, Sant'Antonio E, Palumbo GA, et al. Assessment of the efficacy and tolerability of ruxolitinib for the treatment of myelofibrosis patients in a real-life setting: an Italian MYNERVA Project. Cancer Med. Published online January 27, 2023. doi:10.1002/cam4.5618