Comparison of Systemic Therapies for MPN Subtypes in the Real-World Setting

Clinicohematologic complete response (CHCR) rates demonstrated that pegylated interferon alpha-2a was the most effective treatment for patients with essential thrombocythemia (ET), according to results of a real-world comparison with hydroxyurea and ruxolitinib in patients with myeloproliferative neoplasms (MPNs) reported in Hematology.

The Philadelphia chromosome-negative MPNs (polycythemia vera [PV], ET, and myelofibrosis [MF]) are rare hematologic malignancies characterized by the clonal proliferation of 1 or more myeloid cell lines.

The aims of this prospective cohort study was to investigate the efficacy and safety of 3 systemic therapies in patients with distinct subtypes of MPN treated outside the setting of a clinical trial, the clinicopathologic characteristics associated with response to these therapies, and the quality of life for patients in these treatment subgroups.

Of the 125 patients included in this study, diagnoses were PV, ET, and MF for 23, 56, and 46 patients. Patients were treated with 1 of 3 modalities: conventional therapy, including hydroxyurea for cytoreduction and anagrelide as an adjunct for platelet control; pegylated interferon alpha-2a; or ruxolitinib.

Median durations of treatment were 20 months, 16 months, and 12 months for those receiving hydroxyurea, pegylated interferon alpha-2a, and ruxolitinib, respectively, and the median duration of follow-up for the entire patient cohort was 36.1 months

For the subgroup of patients with PV, the overall response rate (ORR) at a median treatment duration of 6 months was 82% and was similar for those with PV treated with the 3 modalities. However, the CHCR rate was higher for those treated with hydroxyurea (67%) or pegylated interferon alpha-2a (56%) compared with ruxolitinib (20%). Regarding results of genomic profiling, only mutations in CREBBP were significantly associated with a worse ORR (P =.04).

Regarding the subgroup of patients with ET, the ORR at a median treatment duration of 6 months was 99%, even though the CHCR rate was 77%, 89%, and 43% for those treated with hydroxyurea, pegylated interferon alpha-2a, and ruxolitinib, respectively. No association was found between a specific gene mutation and treatment outcome in this subgroup.

Although no patients in the subgroup with MF achieved a complete response with treatment, 48% experienced clinical improvement (CI). CI was particularly notable in those treated with ruxolitinib (70%) and to a lesser extent in patients receiving pegylated interferon alpha-2a (32%), but not in the hydroxyurea-treated patients (0%). Furthermore, in the cohort of patients with MF, disease characterized by a JAK2 V617F mutation was associated with significantly higher treatment responses.

The adverse event (AE) profiles for patients receiving the 3 treatment modalities were distinct, with grade 1/2 neutropenia occurring in 17%, 24%, and 0% of those receiving hydroxyurea, pegylated interferon alpha-2a, and ruxolitinib, respectively. Rates of grade 3/4 adverse events were 0%, 7%, and 9%, respectively. Patients treated with pegylated interferon alpha-2a were most likely to experience grade 1/2 fatigue (24%) and hepatotoxicity (24%).

Other study findings for the entire MPN cohort included a reduction in spleen size only for those patients treated with ruxolitinib. In addition, a comparison of those patients treated with ruxolitinib vs pegylated interferon alpha-2a and hydroxyurea showed significantly greater improvement in patient quality of life (P <.001).

In their concluding remarks, the study investigators commented, “Prospective comparative studies between these two modalities [pegylated interferon alpha-2a and ruxolitinib] are needed in order to critically appraise their relative merits in different MPNs.”