Ruxolitinib and interferon alfa induce superior rates of complete peripheral blood count remission compared to anagrelide in hydroxyurea-exposed essential thrombocythemia Free

Essential thrombocythemia is a myeloproliferative neoplasm characterized by elevated platelets and a predilection for thrombotic events. Patients deemed to have high risk by the revised IPSET-Thrombosis model are routinely started on cytoreductive therapies to reduce risk for thrombosis. Hydroxyurea (HU) is a commonly prescribed front-line therapy to achieve a response as defined by the European Leukemia Network (ELN) which includes reduction of platelet (PLT) and white blood cell (WBC) counts, but the optimal 2^nd-line therapy in ET patients intolerable or resistant to HU is largely unknown. This study aims to compare complete peripheral blood count remission (CPBCR) in HU-exposed ET patients between the commonly prescribed 2^nd-line agents including Anagrelide (ANA), Ruxolitinib (RUX), and Interferon Alfa (IFN)—comprised of both Peginterferon Alfa-2a (PEG) and Ropeginterferon Alfa-2b-njft (ROPEG).

We implemented a pairwise matched cohort analysis utilizing the cross-institutional Epic Cosmos dataset, a single vendor database of more than 299 million patients and 15.5 billion encounters. ET patients were identified by ICD-10 code and a PLT count ≥ 450 x 10⁹/L treated between December 2010 - December 2024. Patients initially treated with HU were queried, and 2^nd-line treatment groups (ANA, RUX, and IFN) were compared by logistic regression after propensity score matching for age, sex, race, and baseline PLT and WBC count. Patients with ICD-10 codes for Myelofibrosis between the initial date of ET diagnosis and the initiation of 2^nd-line therapy were excluded. The primary endpoint was CPBCR as defined by PLT ≤ 400 x 10⁹/L and WBC < 10 x 10⁹/L after 12 ± 1 months of 2^nd-line therapy.

Out of 589,340 possible ET patients queried, a subset of 76,691 patients were initially prescribed HU. The number of patients prescribed 2^nd-line therapies with available PLT and WBC results at baseline and at the primary endpoint at 12 ± 1 months include 221 ANA, 310 RUX, and 129 IFN (99 PEG and 30 ROPEG) patients. CPBCR was achieved in 212 (32.1%) patients overall, and in the subset of 45(20.4%) ANA-treated, 104 (33.5%) RUX-treated, and 63 (48.8%) IFN-treated patients. In pairwise matched comparisons, ANA was inferior to IFN (hazard ratio[HR] 1.55, p < 0.001) and ANA was inferior to RUX (HR 1.45, p = 0.002). Furthermore, IFN was superior compared to RUX in achieving CPBCR (HR 0.65, p=0.004).

Here, we present the largest known comparison of cytoreductive agents in HU-exposed ET patients revealing that though ANA is a commonly prescribed 2^nd-line cytoreductive agent, ANA may induce inferior rates of CPBCR at 1 year of therapy compared to either RUX or IFN. Furthermore, we reveal that IFN, which includes both PEG and ROPEG, may have superior CPBCR rates compared to RUX when matched for age, sex, race, and baseline blood counts. Analyses regarding rates of thrombosis and transformation to myelofibrosis are ongoing and will be presented at the conference. Though the criteria for CPBCR are synonymous with the laboratory parameters of the ELN criteria, spleen response assessment is not available within the Epic Cosmos database to fully characterize ELN response. Regardless, these findings provide preliminary guidance in regards to optimal 2^nd-line cytoreduction for ET patients after initial HU therapy, which warrants further prospective evaluation.