Splenomegaly

Current understanding

Spleen enlargement causes early satiety, abdominal discomfort, pancytopenia. Manage via JAK inhibitors, splenectomy, or radiation.

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 — Validation of MFSAF v4.0 in primary and secondary MF confirmed content validity and reliability of its early-satiety and abdominal-discomfort/pain items, anchoring splenomegaly-related symptom capture in MF trials with a 1–2-point meaningful change threshold. (novelty: 3)
• 2026-08-03 — Spatially resolved transcriptomic profiling of myelofibrosis spleen reveals compartment specific niche programs.: Spatial whole-transcriptome profiling of MF spleen defines three compartment-specific niche programs — intravascular endothelial/vascular-stress, perivascular fibro-remodeling with CXCL12 retention cues, and red-pulp EMH with S100A8/A9 alarmins — reframing splenomegaly as a structured division of microenvironmental labor rather than bulk EMH and nominating compartment-selective targets (CXCL12 axis, S100 alarmins, endothelial stress) beyond JAK inhibition. (novelty: 4)
• 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 notes that non-splenic hematopoietic masses often coexist with progressive splenomegaly and respond to the same ruxolitinib and radiotherapy modalities used for spleen-directed palliation, extending JAK inhibition as a shared control strategy for both splenic and extrasplenic hematopoietic tissue. (novelty: 3)
• 2026-09-01 — Matching-Adjusted Indirect Comparison of Gecacitinib, Fedratinib, Pacritinib, and Momelotinib in Second-Line Myelofibrosis Therapy.: 2026 — Matching-adjusted indirect comparison in ruxolitinib-pretreated MF ranked gecacitinib above fedratinib, pacritinib, and momelotinib on spleen volume response, offering cross-trial comparative-effectiveness data for second-line JAK inhibitor selection in spleen-directed therapy. (novelty: 3)
• 2026-08-23 — Sequential High-Dose Ruxolitinib and Low-Dose Splenic Irradiation for Pretransplant Management of Splenomegaly Before Allogeneic Hematopoietic Cell Transplantation With Fludarabine/Busulfan-Based Conditioning in Myelofibrosis.: Small retrospective series — sequential high-dose ruxolitinib followed by low-dose splenic irradiation produced stepwise pretransplant spleen reduction with encouraging engraftment and early survival in MF patients receiving fludarabine/busulfan-based allo-HCT, extending the high-dose ruxolitinib pretransplant strategy with a radiation add-on for residual splenomegaly. (novelty: 3)
• 2026-06-02 — Selinexor Plus Ruxolitinib in Janus Kinase Inhibitor-Naïve Myelofibrosis: Phase III SENTRY Trial.: 2026 — Phase III SENTRY (JAKi-naïve MF): selinexor + ruxolitinib significantly improved SVR35 at week 24 vs ruxolitinib alone with an early OS signal, reinforcing XPO1 inhibition as a spleen-directed add-on strategy (with expected additive hematologic toxicity). (novelty: 3)
• 2026-08-01 — A dynamic prognostic model for polycythemia vera long-term outcomes in patients treated with ruxolitinib.: PV-RR6, a dynamic 6-month prognostic score for ruxolitinib-treated polycythemia vera, uses spleen length reduction (alongside ruxolitinib dose intensity and ongoing phlebotomy need) to stratify 5-year event-free survival into low- (~89%), intermediate- (~71%), and high-risk (~39%) groups — positioning early spleen response as a monitorable marker of long-term outcome in PV. (novelty: 3)
• 2026-08-25 — Spatial profiling of the spleen in mouse and human myelofibrosis reveals complement-driven immune-stromal interactions as a therapeutic target.: Preclinical spatial profiling of mouse and human myelofibrotic spleens identifies complement C3-driven reprogramming of splenic reticular cells into inflammatory pro-fibrotic states; genetic or pharmacologic C3 blockade restored splenic architecture and reduced splenomegaly and bone marrow fibrosis, nominating complement inhibition as a novel spleen-directed therapeutic axis. (novelty: 5)
• 2025-11-20 — Splenic Artery Aneurysm Associated with Myelofibrosis Managed by Coil Embolization.: Case report — ruxolitinib-induced splenomegaly reduction in JAK2 V617F-positive secondary myelofibrosis enabled safe spleen-preserving coil embolization of a splenic artery aneurysm, illustrating a potential role for JAK inhibitors as hemodynamic bridging therapy before endovascular intervention in MF-associated vascular complications. (novelty: 3)
• 2026-06-23 — Galectin-1 Fuels Monocyte Hyperinflammation and Represents a Novel Therapeutic Target in Myeloproliferative Neoplasms.: Preclinical study identifies galectin-1 (LGALS1) as a driver of monocyte hyperinflammation via TLR4–NF-κB signaling in MPN; genetic or pharmacologic inhibition reduced splenomegaly (alongside leukocytosis and thrombosis) in MPLW515L mice, nominating LGALS1 as a novel spleen-directed inflammatory target. (novelty: 5)
• June 12-15 — Advancing Frontiers in Myeloproliferative Neoplasms - EHA 2025 Congress Review: EHA 2025 review highlights converging spleen-directed strategies in myelofibrosis: elritercept (anemia-focused with symptom benefit), pelabresib + ruxolitinib (phase III MANIFEST-2), and INCA035784, a T cell–redirecting antibody targeting mutant CALR. (novelty: 3)
• 2026-06-13 — Lilly to present initial clinical data for first-in-class type II JAK2 inhibitor in patients with previously treated myelofibrosis at the 2026 EHA Annual Meeting: AJ1-11095, a first-in-class type II JAK2 inhibitor, reported encouraging safety and spleen volume reduction in myelofibrosis patients previously treated with (and refractory to) type I JAK inhibitors, across JAK2, MPL, and CALR type 1/2 mutations — initial clinical data slated for 2026 EHA. (novelty: 4)
• 2026-06-03 — A Study to Compare Elritercept to Placebo in Adults With Myelofibrosis and Anemia Who Are Taking Ruxolitinib: Randomized placebo-controlled trial of elritercept added to ruxolitinib in MF with anemia includes MF symptom burden (encompassing splenomegaly-related symptoms) among endpoints, advancing the earlier-phase elritercept program into RCT testing. (novelty: 3)
• May 21, 20 — CALR Mutation–Directed Agents and Targeted Therapies Represent Key Research Avenue in MPN Management: Review synthesis reaffirms SENTRY phase 3 met its co-primary spleen volume reduction endpoint (selinexor + ruxolitinib first-line MF) and contextualizes it alongside MANIFEST-3, IMpactMF, and INCA033989 as emerging spleen-directed combination/targeted strategies. (novelty: 3)
• March 24, — ASH 2025: Myelofibrosis Roundup: ASH 2025 — Phase 1 data on INCA033989 (first-in-class anti-mutant CALR antibody) reported spleen volume reduction in myelofibrosis patients including those resistant/intolerant to JAK inhibitors, introducing a disease-modifying immunologic mechanism with spleen-directed effects distinct from JAK/BET/BCL-2/XPO1 combinations. (novelty: 5)
• January 21 — Zavabresib Earns FDA Orphan Drug Designation in Myelofibrosis: Zavabresib (OPN-2853), a selective BET inhibitor, received FDA orphan drug designation for myelofibrosis with reported durable spleen reduction when combined with ruxolitinib in patients with inadequate ruxolitinib response — adds another ruxolitinib add-on combination strategy for spleen-directed therapy. (novelty: 3)
• 2026-02-04 — 18F-FAPI PET/MRI Imaging in Myelofibrosis: a Prospective Observational Study.: Prospective observational study evaluating 18F-FAPI PET/MRI vs 18F-FDG PET/CT for systemic fibrosis assessment in myelofibrosis, which may offer a non-invasive imaging tool to characterize splenic fibroblast activation contributing to splenomegaly (correlated with bone marrow biopsy and prognosis). (novelty: 4)
• 2026-02-05 — A Study of Elritercept Alone or Together With Ruxolitinib in Adults With Myelofibrosis: Early-phase elritercept ± ruxolitinib trial in myelofibrosis includes MF symptom assessment (which encompasses splenomegaly-related symptoms) as part of its endpoints, though the primary focus is anemia rather than spleen volume reduction. (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 RCT evaluating navitoclax (BCL-2/BCL-XL inhibitor) + ruxolitinib vs ruxolitinib alone in myelofibrosis, with spleen volume reduction as primary endpoint — adds to the growing class of ruxolitinib add-on combination strategies for spleen-directed therapy. (novelty: 3)
• 2026-03-11 — High Dose Ruxolitinib and Allogeneic Stem Cell Transplantation in Myelofibrosis Patients With Splenomegaly: Early-phase trial evaluating high-dose ruxolitinib combined with busulfan-based conditioning to reduce splenomegaly prior to allogeneic stem cell transplant in myelofibrosis, addressing spleen size as a barrier to transplant success. (novelty: 3)
• 2026-04-09 — Comparing Momelotinib and Ruxolitinib in People With Untreated Myelofibrosis and Low Blood Cell Counts: Head-to-head trial comparing momelotinib vs ruxolitinib as first-line therapy in untreated myelofibrosis patients with cytopenias, using spleen volume reduction as primary endpoint — relevant for spleen-directed therapy choice in the cytopenic MF subgroup. (novelty: 3)
• 2026-03-24 — Karyopharm Phase 3 SENTRY Trial in Myelofibrosis Met First Co-Primary Endpoint: 2026 — Phase 3 SENTRY trial: selinexor + ruxolitinib met co-primary endpoint of spleen volume reduction vs ruxolitinib alone in myelofibrosis (with 32% vs 24% achieving ≥20% VAF reduction), supporting combination XPO1 inhibition as a spleen-directed strategy. (novelty: 4) (novelty: 4)
• 2026-01-06 — Key Oncology Drugs Granted FDA Designations in January 2026: CK0804, an allogeneic Treg cell therapy, received FDA orphan drug designation (Jan 2026) based on reported reductions in spleen volume in heavily pretreated myelofibrosis patients (disease-modifying mechanism, but with direct symptom-area implications). (novelty: 4)

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