Quality of Life Evaluation for Patients on Ropeginterferon Alpha-2b Versus Other Best Available Therapies

Polycythemia vera (PV) and essential thrombocythemia (ET) have symptomatic disease burden: fatigue, concentration difficulty, insomnia, sexual dysfunction, night sweats, pruritus, and early satiety. Symptoms stem from inflammatory dysregulation, splenomegaly, psychosocial stressors, and transformation to myelofibrosis and acute leukemia (Geyer 2017); all impairing quality of life (QoL). Treatment with interferons decreases expression of prothrombotic and inflammatory genes compared to hydroxyurea (Emanuel 2012). The validated Myeloproliferative Symptom Assessment Form (MPN-SAF) and scales by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC Q-30) have shown correlation with overall QoL (Emanuel 2012).

We quantified changes in QoL for PV and ET patients treated with ropeginterferon alfa-2b versus other best-available therapies (i.e. hydroxyurea, ruxolitinib, pegylated interferon, fedratinib) and previously untreated patients using MPN-SAF and EORTC-Q30 at intervals throughout treatment, including baseline assessments. We evaluated time to achieve complete hematologic remission (CHR) and mutational status; DNMT3A mutations have shown decreased responses to interferon (Usart 2024; Knudsen 2022).

Understanding what symptoms or measures of QoL change with ropeginterferon alpha-2b compared to other therapies may help us determine ways to help patients adhere to treatment and reap the benefits of this disease-modifying therapy. Longer exposure to therapy (>12 months) appears to be a principal factor in achieving deeper remissions (Larsen 2009).

We present data for 38 patients over the course of 6 to 18 months of treatment on ropeginterferon alfa-2b.

Patients were identified with PV or ET undergoing treatment at the Huntsman Cancer Institute planning to start treatment with ropeginterferon alfa-2b. 3 cohorts were formed-cohort 1: previous therapy with pegylated interferon, cohort 2: previous therapy with other available treatments, cohort 3: previously untreated. Participants agreed to participate in this Institutional Review Board approved retrospective/prospective study and completed QoL surveys (MPN-SAF and EORTC-Q30) prior to first injection. Surveys were completed every 2 weeks for the first 12 weeks, monthly until 12 months, and every 3 months for 2 years.

Blood counts were evaluated at baseline, week 4, week 8, week 12, and then every 3 months. A CHR was defined as per the World Health Organization (WHO) guidelines as a WBC<10k/uL and Plt count<400k/uL. Hematocrit goal was adjusted for altitude for persons living between 1000 and 1999m (mean hemoglobin levels of 15.6g/dl for males and 13.4 g/dl for females) resulting in a 2.7% increase from a Hct of 45%, as per the WHO guidelines, to a hematocrit of 47.7% (Grassmann 2019). Therefore, we defined CHR by a Hct of <48%. Blood counts were evaluable if ± 30 days of the target collection date. Mutation status was determined using Myeloid NGS results via ARUP Laboratories in Salt Lake City collected prior to ropeginterferon alfa-2b initiation.

Of 38 patients, 20 were previously treated with hydroxyurea, 2 with ruxolitinib, 1 with fedratinib, 12 with pegylated interferon-alfa, and 3 were previously untreated. 10 patients were in remission when they started ropeginterferon alfa-2b. The mean time to CHR was 53.8 weeks for cohort 1, 47 weeks for cohort 2, and 38.5 weeks for cohort 3. The only mutation found to impact time to remission was DNMT3A (p<0.05). Cohorts 1 and 2 had a decrease in scores (p<0.05) for the MPN-SAF and EORTC-Q30, indicating improvement in symptom burden and quality of life. Cohort 3 was too small to evaluate. Those transitioning from hydroxyurea had improvement (p<0.05) in abdominal pain, shortness of breath, bone pain, concentration difficulty, and most notably early satiety (p=.006). Itching was worse in cohort 2 and 3 on ropeginterferon alfa-2b, however with p>0.05 and so not statistically significant. 29% of patients discontinued therapy prior to 2 years, notably for fatigue, anxiety/depression, and dermatologic toxicity.

Ropeginterferon alpha-2b is an effective disease modifying therapy for PV and ET as it increases quality of life and decreases symptom burden compared to other available therapies. Whether the molecular benefit of this therapy plays a role in the patients' everyday experience of their disease and treatment remains to be determined.

Tashi:PharmaEssentia: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Cogent: Membership on an entity's Board of Directors or advisory committees, Research Funding; Italfarmaco: Research Funding; Telios: Research Funding; CITI Biopharma: Honoraria; Blueprint: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Study Steering Committee, Research Funding. Prchal:AbbVie: Research Funding; PharmaEssentia: Research Funding.