The combination of azacitidine/ruxolitinib tablets can prolong the survival of patients with advanced MPNs

A multinational team reports new data in one of the most difficult areas of hematology: patients with myeloproliferative neoplasms (MPN) who progress to accelerated or blast phase but are ineligible for intensive chemotherapy or transplantation. The retrospective study, published in HemaSphere, followed 149 such patients treated between 2019 and 2023.

This group was elderly, with a median age of 75, and most had multiple health problems that precluded aggressive treatment. Sixty patients were treated with azacitidine alone, while 89 patients were treated with Ruxolitinib, venetoclax or other targeted drugs in combination. The median survival for the entire cohort was just over8 months. Only about one in eight patients are alive at three years. The prognosis of the blast phase is worse than that of the accelerated phase, and patients with complex cytogenetic features or TP53 mutations have particularly poor survival rates.

Amid this bleak picture, one signal stands out. Compared with patients treated with azacitidine alone or azacitidine plus venetoclax, patients taking azacitidine plus ruxolitinib lived longer, an average of approximately 18 months, while those treated with azacitidine and venetoclax lived less than a year. This difference was most pronounced among patients without high-risk genetic lesions.

This benefit did not meet the strict threshold of statistical significance, and the design of the study left room for bias. Treatment assignment was not random, and healthy patients may be more likely to receive the combination regimen. The authors acknowledge these limitations but feel that the consistency of the ruxolitinib signal warrants further investigation.

At the same time, venetoclaxprovided no survival benefit in patients with de novo or secondary acute myeloid leukemia. Why BCL-2 inhibition fails in this MPN-derived environment remains uncertain, but the data suggest that there may be enough differences in biology to attenuate its effects.

For clinicians, this information is practical if not changing practice. Azacitidine remains the mainstay for patients who cannot tolerate more intensive treatments, but it hardly buys time by itself. The addition of ruxolitinib may meaningfully extend survival in a subset of patients, although this approach should be carefully weighed, preferably in the context of a clinical trial.

For researchers, these findings heighten the challenge. Regardless of treatment regimen, patients with TP53 mutations or complex cytogenetics have a poor prognosis. None of the treatments in the current study could bend the curve in this group, underscoring the urgency of developing strategies that target the risk of undesirable molecules.

The authors did not call azacitidine plus ruxolitinib a new standard. But in a disease setting where survival is measured in months, the likelihood that selected patients will live as long as a year and a half is noteworthy. This study provides a baseline for ongoing and future experiments and a reminder that even incremental progress is important for advanced, versatile neural networks.

References:https://www.docwirenews.com/post/azacitidine-ruxolitinib-combo-extends-survival-in-advanced-mpns