Fatigue

Current understanding

Most common MPN symptom across all subtypes; multifactorial driven by cytokines, anemia, and splenomegaly.

Evidence log

• 2026-06-12 — Assessment of the MFSAF v4.0 and PROMIS Fatigue 7a to Measure Outcomes in Myelofibrosis: Validation from a Non-interventional Mixed Methods Study.: 2026 — Mixed-methods non-interventional validation established MFSAF v4.0 and PROMIS Fatigue 7a as content-valid, reliable, and construct-valid PRO instruments in primary and secondary MF, with a patient-defined meaningful within-item change of 1–2 points supporting their use as fatigue endpoints in MF trials. (novelty: 3)
• 2026-06-30 — A systematic review of 47 published cases of extramedullary hematopoiesis in myelofibrosis: clinical patterns, treatment responses, and prognostic implications.: Systematic review of 47 atypical EMH cases in MF frames these lesions as markers of advanced, symptomatic disease contributing to the overall systemic symptom burden (including fatigue and constitutional symptoms) that improves with ruxolitinib in most reported cases. (novelty: 3)
• 2026-09-01 — Matching-Adjusted Indirect Comparison of Gecacitinib, Fedratinib, Pacritinib, and Momelotinib in Second-Line Myelofibrosis Therapy.: 2026 — MAIC in ruxolitinib-pretreated MF found gecacitinib superior on total symptom score response vs fedratinib, pacritinib, and momelotinib, with lower GI adverse-event and discontinuation rates — indirect comparative evidence for symptom-directed second-line JAK inhibitor choice. (novelty: 3)
• 2026-06-02 — Selinexor Plus Ruxolitinib in Janus Kinase Inhibitor-Naïve Myelofibrosis: Phase III SENTRY Trial.: 2026 — Phase III SENTRY confirmed that selinexor + ruxolitinib in JAKi-naïve MF did NOT improve AbsTSS despite meeting the spleen endpoint, adding late-phase confirmatory evidence to the recurring spleen–symptom dissociation in MF combination trials. (novelty: 3)
• 2026-07-22 — Disease Burden, Inadequate Hematocrit Control, and Thromboembolic Events in Patients with Polycythemia Vera Despite Current Standard of Care Treatment: A Retrospective Claims Study.: 2026 — Real-world US claims analysis of 11,311 PV patients quantified ongoing symptom burden (including fatigue) alongside uncontrolled HCT and thromboembolic events under current SoC, underscoring that phlebotomy/cytoreduction alone leaves substantial residual symptom burden in PV. (novelty: 3)
• 2026-06-03 — A Study to Compare Elritercept to Placebo in Adults With Myelofibrosis and Anemia Who Are Taking Ruxolitinib: Randomized placebo-controlled (late-phase) trial of elritercept add-on to ruxolitinib in myelofibrosis with anemia evaluates fatigue and physical function alongside anemia response, providing the first RCT-level evidence on this activin ligand trap’s impact on the anemia–fatigue axis. (novelty: 3)
• March 24, — ASH 2025: Myelofibrosis Roundup: ASH 2025 — Phase 1 INCA033989 (anti-mutant CALR antibody) reported symptom reduction and anemia improvement alongside high treatment retention (87%) in myelofibrosis, suggesting a novel CALR-neoepitope-targeted route to the anemia–fatigue and cytokine–fatigue axes independent of JAK inhibition. (novelty: 5)
• 2026-05-14 — INCB000928 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Anemia Due to Myeloproliferative Disorders: Phase 1/2 dose-escalation/expansion trial of INCB000928 as monotherapy or combined with ruxolitinib in myelofibrosis patients with transfusion-dependent or symptomatic anemia, adding another investigational anemia-directed agent to the fatigue-via-anemia therapeutic axis alongside luspatercept, elritercept, and nelfinavir. (novelty: 4)
• 2026-02-05 — A Study of Elritercept Alone or Together With Ruxolitinib in Adults With Myelofibrosis: Early-phase trial of elritercept (novel TGF-β superfamily/activin ligand trap) alone or with ruxolitinib in myelofibrosis evaluates effects on anemia and MF symptom burden, adding another anemia-directed agent to the fatigue-via-anemia therapeutic axis alongside luspatercept and nelfinavir. (novelty: 4)
• 2026-02-04 — Treating Anemia in Myelofibrosis With Repurposed Drugs (Nelfinavir) That Restore Iron Delivery to the Bone Marrow: 2026 — Phase I/II trial of repurposed HIV protease inhibitor nelfinavir in myelofibrosis targeting anemia (a major upstream driver of MF fatigue) via restoration of iron delivery to the bone marrow, with serum fibrosis biomarkers as a secondary readout — novel mechanistic angle on the anemia–fatigue axis distinct from ESAs, luspatercept, or transfusion support. (novelty: 4)
• 2026-03-23 — Study of Oral Navitoclax Tablet In Combination With Oral Ruxolitinib Tablet When Compared With Oral Ruxolitinib Tablet To Assess Change In Spleen Volume In Adult Participants With Myelofibrosis: Phase 3 navitoclax + ruxolitinib vs ruxolitinib trial in myelofibrosis includes symptom burden as a secondary outcome, providing further data on whether BCL-2/BCL-XL inhibition added to JAK inhibition translates spleen response into patient-reported symptom improvement. (novelty: 3)
• 2026-03-27 — Curcumin to Improve Inflammation and Symptoms in Patients With Clonal Cytopenia of Undetermined Significance, Low Risk Myelodysplastic Syndrome, and Myeloproliferative Neoplasms: 2026 — Phase II trial evaluating curcumin (C3 complex/Bioperine) supplementation in CCUS, LR-MDS, and MPN patients with inflammation and symptom burden (including fatigue) as endpoints — first prospective trial of curcumin as an anti-inflammatory integrative intervention in this population. (novelty: 3)
• 2026-04-09 — ENERGIA: Personalized Exercise Program for Fatigue in Patients With Myeloproliferative Neoplasms and Chronic Myeloid Leukemia: 2026 — ENERGIA trial: prospective study of 12-week personalized aerobic + resistance exercise program in MPN/CML patients evaluating feasibility, safety, and efficacy on fatigue, physical function, and inflammatory biomarkers — first supervised exercise intervention trial in this population with biomarker endpoints. (novelty: 3) (novelty: 3)
• 2026-03-24 — Karyopharm Phase 3 SENTRY Trial in Myelofibrosis Met First Co-Primary Endpoint: 2026 — Phase 3 SENTRY trial of selinexor + ruxolitinib in myelofibrosis FAILED the symptom burden (TSS) co-primary endpoint despite meeting the spleen volume endpoint, illustrating the recurring dissociation between spleen response and patient-reported symptom improvement in MF combination trials. (novelty: 4) (novelty: 4)
• 2026-01-06 — Key Oncology Drugs Granted FDA Designations in January 2026: FDA orphan drug designation for CK0804 (allogeneic Treg therapy, Jan 2026) cited reductions in symptom burden and transfusion burden alongside spleen volume in heavily pretreated myelofibrosis patients. (novelty: 4)

Open questions

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