(049) Comparison of Weight Gain in Male and Female Patients Treated with Ruxolitinib for Myeloproliferative Neoplasms

Poster Abstract: Background
Myeloproliferative neoplasms (MPNs) encompass malignancies of the bone marrow characterized by clonal proliferation of myeloid cells. Aberrant activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is a common contributor to MPN pathogenesis, and ruxolitinib, a JAK1/2 tyrosine kinase inhibitor, has demonstrated extended overall survival and improved symptomatology in patients with MPNs. Weight gain is a common side effect of ruxolitinib, affecting upwards of 69% of patients with a median long-term weight gain of 6.7%.

The JAK2/STAT3 pathway induces weight gain by mediating hypothalamic receptor signals that provide feedback to suppress appetite after eating. Anecdotally, weight gain is more profound in female patients, which coincides with evidence that plasma leptin concentrations are higher in female populations. Still, weight gain disparities between sexes have not been described, which is critical for anticipating treatment-related health changes and counseling of adverse effects by pharmacists.

Objectives
Primary

Objective: To compare median percentage weight change from baseline through 48 weeks of treatment between male and female patients receiving ruxolitinib for an MPN.

Secondary

Objective: To compare hematologic response in patients who did and did not experience weight gain to assess a potential impact on effectiveness.

Methods

Design: This is a single-center, retrospective cohort study conducted at the Huntsman Cancer Institute in Salt Lake City, Utah.

Patients: Included patients must be aged 18 years or greater who initiated ruxolitinib to treat an MPN, including polycythemia vera, primary myelofibrosis, or essential thrombocythemia. Patients must have received at least 46 weeks of treatment with a documented week 0 and week 48 body weight. Patients will be excluded if they underwent a non-bariatric weight-altering surgery (e.g., amputation), but they will be included if they received a medication for weight loss or a bariatric surgery to account for patients who may have sought weight loss interventions for ruxolitinib-associated weight gain.

Data and Statistical Analysis: Data will be collected via automated pull and manual chart review of the Epic Hyperspace® electronic medical record. Data will be stored in a REDCap® database with patient identifiers kept in a password-protected Microsoft Excel® spreadsheet. Data will be summarized using descriptive statistics and compared using a t-test for continuous variables and a chi-square test for categorical variables. Linear regression models will be constructed on the primary endpoint using sex, age, race/ethnicity, ECOG performance score, and myeloproliferative neoplasm type.

Results
Results pending.

Discussion/Conclusions
Discussion and conclusions pending.

References (must also be included in final poster): 1. Venugopal S, Mascarenhas J. Novel therapeutics in myeloproliferative neoplasms. J Hematol OncolJ Hematol Oncol. 2020;13(1):162. doi:10.1186/s13045-020-00995-y

2. Penna D. New Horizons in Myeloproliferative Neoplasms Treatment: A Review of Current and Future Therapeutic Options. Medicina (Mex). 2021;57(11):1181. doi:10.3390/medicina57111181

3. McMullin MF, Anderson LA. Aetiology of Myeloproliferative Neoplasms. Cancers. 2020;12(7):1810. doi:10.3390/cancers12071810

4. Tefferi A, Vaidya R, Caramazza D, Finke C, Lasho T, Pardanani A. Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29(10):1356-1363. doi:10.1200/JCO.2010.32.9490

5. Tefferi A, Pardanani A. Myeloproliferative Neoplasms: A Contemporary Review. JAMA Oncol. 2015;1(1):97-105. doi:10.1001/jamaoncol.2015.89

6. Verstovsek S, Mesa RA, Gotlib J, et al. A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis. N Engl J Med. 2012;366(9):799-807. doi:10.1056/NEJMoa1110557

7. Harrison CN, Vannucchi AM, Kiladjian JJ, et al. Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis. Leukemia. 2016;30(8):1701-1707. doi:10.1038/leu.2016.148

8. Mascarenhas J, Hoffman R. Ruxolitinib: the first FDA approved therapy for the treatment of myelofibrosis. Clin Cancer Res Off J Am Assoc Cancer Res. 2012;18(11):3008-3014. doi:10.1158/1078-0432.CCR-11-3145

9. Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012;366(9):787-798. doi:10.1056/NEJMoa1110556

10. Mollé N, Krichevsky S, Kermani P, Silver RT, Ritchie E, Scandura JM. Ruxolitinib can cause weight gain by blocking leptin signaling in the brain via JAK2/STAT3. Blood. 2020;135(13):1062-1066. doi:10.1182/blood.2019003050

11. Greenfield G, McMullin MF. Ruxolitinib: gaining more than intended. Blood. 2020;135(13):983-984. doi:10.1182/blood.2020005135

12. Couillard C, Mauriège P, Prud’homme D, et al. Plasma leptin concentrations: gender differences and associations with metabolic risk factors for cardiovascular disease. Diabetologia. 1997;40(10):1178-1184. doi:10.1007/s001250050804