Real-World Study Shows Promising Efficacy, Safety of Ropeg in MPN

Ropeginterferon alpha-2b (Ropeg) is a promising treatment option for certain myeloproliferative neoplasms, according to a new study which demonstrated the efficacy and safety of the novel pegylated interferon-alpha in a real-world setting.

Ropeg was recently approved for the treatment of polycythemia vera (PV) in Europe, and in June, the FDA accepted a Biologics Licensing Application for the treatment to be used in patients with PV in the absence of symptomatic splenomegaly.

In the current study, the treatment showed promise in Philadelphia-negative MPNs, which include PV, essential thrombocythemia, and primary myelofibrosis. In 8 evaluable patients, Ropeg elicited a 62.5% peripheral blood count complete remission (PBCR) rate after a median of 16 weeks.

“Significantly, unlike the patient population enrolled in the prospective PROUND/CONTI-PV trial in which many of them were treatment-naïve, most of our cases had run out of options for their refractory disease, indicating the substantial potency of this novel agent,” explained the researchers. They continued, “the relatively long duration of the treated patients also provides a sneak peek in how Ropeg can be incorporated into our daily practice in the future.”

Most of the treatment-related adverse events (AEs) were minor, leading the researchers to determine that Robeg was well tolerated. No patient discontinued treatment due to side effects, and there was a total of 4 Grade 3 or 4 hematological AEs.

Ropeg was initiated due to poorly controlled erythrocytosis in 3 patients and thrombocytosis in 5 patients. Baseline hematocrit (Hct) levels in the 3 patients with erythrocytosis were not “exaggeratingly highly” as a result of preceding therapy with concurrent hydroxyurea and phlebotomies. In 2 of these patients, Hct was considered unsatisfactory, although each experienced reduced phlebotomy frequencies by 83% and 50%. One of these patients achieved PBCR after 56 weeks.

For the 5 patients with refractory thrombocytosis, the researchers observed a rapid and dramatic drop in platelet counts, typically within the first 8 weeks of treatment. Three of these patients achieved PBCR.

Two-thirds of patients experienced an increase in plasma hepcidin levels, suggesting the potential of Ropeg to restore normal regulation of erythropoiesis.

When it came to amelioration of symptoms and reduction in spleen size, there were 2 patients with progressive disease and higher initial symptoms scores who did not have an improvement in discomfort. However, 6 of the 7 continuously treated patients who were more symptomatic at baseline responded well. Two patients who had pre-treatment splenomegaly experienced a nearly complete normalization of post-treatment spleen indices.

“Although we failed to identify either any predictor of treatment response or specific patterns of plasma level alteration after Ropeg therapy from a portfolio of cytokines in our patients, we did notice significant decrement in several cytokines in one patient, which coincided with substantial decline in JAK2 mutant AB, symptom score, and spleen size,” researchers wrote.

“With the inflammatory cytokine being produced by the malignant clone and the marrow stromal cells, the alleviation of the cytokine storm in this patient indicates that Ropeg therapy could lead to gradual restoration of normal hematopoiesis as well as orderly restitution of the damaged marrow niche,” they concluded.

Reference: Huang C, Wu Y, Hsu C, et al. Real-world experience with Ropeginterferon-alpha 2b (Besremi) in Philadelphia-negative myeloproliferative neoplasms. J Formos Med Assoc. Published online August 29, 2020. doi: 10.1016/j.jfma.2020.08.021