Long-Term Ruxolitinib Safe, Effective for Polycythemia Vera

Long-term follow-up results from the phase 3 RESPONSE trial show that ruxolitinib is a safe and effective therapy option for patients with polycythemia vera (PV) resistant to or intolerant of hydroxyurea (Lancet Hematol. 2020 Jan 23. Epub ahead of print).

“[PV] is a myeloproliferative neoplasm characterised by excessive proliferation of erythroid, myeloid, and megakaryocytic components in the bone marrow due to mutations in the [JAK2 gene],” explained Jean-Jacques Kiladjian, MD, Centre d'Investigations Cliniques, Hôpital Saint-Louis, Paris, France, and colleagues.

“Ruxolitinib, a JAK 1 and JAK 2 inhibitor, showed superiority over best available therapy in a phase 2 study in patients with…[PV] who were resistant to or intolerant of hydroxyurea,” they continued.

The phase 3 RESPONSE trial aimed to compare the long-term safety and efficacy of ruxolitinib with best available therapy in this patient population. Patients from 109 sites across North America, South America, Europe, and the Asia-Pacific region were enrolled in the study.

Of 342 patients screened for eligibility, 222 were accepted and randomized in a 1:1 ratio to receive ruxolitinib (n = 110) or best available therapy (n = 112). Ruxolitinib was administered at a starting dose of 10 mg twice daily, and best available therapy consisted of hydroxyurea, interferon or pegylated interferon, pipobroman, anagrelide, approved immunomodulators, or observation without pharmacologic treatment.

The primary end point (composite response at 32 weeks) was previously reported by Dr Kiladjian et al. This long-term follow-up analysis evaluated the 5-year durability of primary composite response, complete hematological remission, overall clinico-hematologic response, overall survival, patient-reported outcomes, and safety.

The median time since PV diagnosis was 8.2 years in the ruxolitinib arm and 9.3 years in the best available therapy arm.

Of the 112 patients originally assigned to receive best available therapy, 98 switched to ruxolitinib; no patients continued receiving best available therapy after 80 weeks in the study.

Furthermore, by the final analysis, 6 of the 25 primary responders in the ruxolitinib arm had progressed.

At 5 years follow-up, the probability of maintaining a primary composite response was 74%, the probability of maintaining a complete hematologic remission was 55%, and the probability of maintaining an overall clinico-hematologic response was 67%.

The probability of survival at 5 years in the intention-to-treat analysis (not counting for crossover) was 91.9% with ruxolitinib and 91% with best available therapy.

The most common adverse event (AE) reported in patients receiving ruxolitinib was anemia, although most events were mild-to-moderate in severity. Nonhematologic AEs were generally lower with long-term ruxolitinib than with best available therapy. Rates of thromboembolic events were also lower with ruxolitinib than with best available therapy.

Dr Kiladjian and colleagues reported 2 deaths during therapy in the ruxolitinib arm, including 1 from gastric adenocarcinoma that was deemed ruxolitinib-related.

“We showed that ruxolitinib is a safe and effective long-term treatment option for patients with polycythaemia vera who are resistant to or intolerant of hydroxyurea. Taken together, ruxolitinib treatment offers the first widely approved therapeutic alternative for this post-hydroxyurea patient population,” they concluded.—Janelle Bradley