Tavalisse (fostamatinib) / Rigel, Kissei, JW Pharma, Grifols, Knight Therap, Mitsubishi Tanabe - LARVOL DELTA

Feasibility assessment of indirect treatment comparison between off-label rituximab and novel treatments in patients with warm autoimmune hemolytic anemia (ASH 2025) - "Among the clinical trials included, five studied rituximab, in combination with prednisone, prednisolone, ibrutinib, or bortezomib. Three trials studied fostamatinib, while other studied treatments included pegcetacoplan, sovleplenib, parsaclisib, and rilzabrutinib...Future work should consider de novo sources of real-world evidence for rituximab that more closely align with registrational trial characteristics and endpoint definitions. However, aligning timing of endpoint measurements between registration trials and real-world data to match definitions remains challenging."

Clinical • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology

Disease burden and treatment patterns in patients with previously treated primary immune thrombocytopenia (ITP): A retrospective study using administrative claims data in the United States (ASH 2025) - "Following the initial ITP diagnosis, previously treated patients were identified as those who were currently on ITP treatment and who had received one prior therapy comprising an oral corticosteroid, IVIG, IV anti-D, or platelet transfusion, as well as one or more prior therapies comprising TPO-RA, rituximab, fostamatinib, anti-CD-38 monoclonal antibodies, immunosuppressants, danazol, dapsone, bortezomib, vinca alkaloid, or splenectomy. Conclusions Despite receiving at least one currently available first-line and second-line therapy, in this US-based claims study of patients with primary ITP, a significant proportion continued to experience bleeding events and required rescue therapy. This analysis highlights significant unmet needs for novel therapies for the primary ITP patient population."

Retrospective data • Gynecology • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura

A case for CD38 targeted therapy in multi-refractory immune thrombocytopenia (ASH 2025) - "Initial treatment with high-dose dexamethasone and IVIG was ineffective. He subsequently received rituximab, eltrombopag and avatrombopag...During weeks 8–14, he was treated with romiplostim, a second steroid pulse, mycophenolate, cyclophosphamide, and cyclosporine without response...While this study is ongoing, we present this case to highlight that daratumumab can be associated with a rapid platelet recovery in multi-refractory ITP, was safe and well tolerated with fostamatinib and danazol, and produced a durable response after a finite treatment course (12 weekly doses). In conclusion, for patients with prolonged, severe ITP unresponsive to conventional treatments, daratumumab offers a rational, mechanism-based intervention. Our case contributes to growing evidence supporting anti-CD38 immunotherapy in ITP and underscores the need for clinical trials to more broadly evaluate other plasma cell directed therapies for the treatment of ITP."

Clinical • Autoimmune Hemolytic Anemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Immune Thrombocytopenic Purpura • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Thrombocytopenia • Thrombocytopenic Purpura

Comparative effectiveness of second-line therapies for chronic immune thrombocytopenia: A network meta-analysis of RCTs (ASH 2025) - "The treatment groups were: Avatrombopag (96), Eltrombopag (283), Fostamatinib (101), Rilzabrutinib (133), Romiplostim (2116), and Rozanolixizumab (41)...Rituximab was analyzed indirectly and showed moderate efficacy... This NMA provides a comparative analysis of second-line therapies for chronic ITP, with Rozanolixizumab identified as the most effective treatment. Despite variability in safety profiles, all therapies demonstrated significant clinical benefits, supporting the adoption of personalized treatment strategies."

HEOR • Retrospective data • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura • SYK

Efficacy and safety of spleen tyrosine kinase inhibitors in chronic immune thrombocytopenic purpura: A meta-analysis of randomized controlled trials (ASH 2025) - "SYK inhibitors significantly improve platelet response in chronic ITP without increased thrombotic risk. Fostamatinib and the investigational agent sovleplenib both demonstrated efficacy compared to placebo. These agents may represent promising options for patients with refractory ITP, particularly those at risk of thrombosis from TPO-RAs."

Retrospective data • Cardiovascular • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis • SYK

Real-world treatment patterns and clinical outcomes of therapies in primary immune thrombocytopenia (ASH 2025) - "Patients received oral CS, IVIG, anti-D, or rituximab as 1L and TPO-RA,rituximab, fostamatinib, splenectomy, or immunosuppressants as 2L treatments. Among 3287 eligible patients diagnosed with ITP who initiated a 1L treatment, median (IQR) ageat diagnosis was 64.6 (49.8-75.4) years, 59.4% were female, and median (IQR) time from ITP diagnosis toindex date was 0.1 (0-6.9) months. This contemporary study from US EHRs confirmed that oral CS were the main 1L therapy forITP and revealed that a substantial proportion of patients either discontinued or recycled oral CS withoutinitiating guideline-recommended 2L treatment. During 1L follow-up, approximately one-thirdexperienced ≥1 BRE and nearly one-quarter used ≥1 rescue therapy. Substantial variations in baselineand follow-up platelet counts were observed."

Clinical • Clinical data • HEOR • Real-world • Real-world evidence • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura

Daratumumab can lead to long-lasting remissions in patients with refractory immune thrombocytopenia but with a high incidence of severe infections (ASH 2025) - "In addition, 2 patients hadantibodies against GPIIb-IIIa (acquired Glanzmann syndrome, n=1) and GPVI (n=1) responsible for chronicbleeding symptoms.Median ITP duration was 78 months [range 4-594], and patients had previously received a mediannumber of 8 [range, 3-12] treatment lines for ITP, including corticosteroids (100%), rituximab (100%),intravenous immunoglobulin (95%), thrombopoietin receptor agonists (95%; including eltrombopag[90%] and romiplostim [86%]), mycophenolate mofetil (81%), splenectomy (71%), fostamatinib (48%), andone or more other immunosuppressive drug (43%). However, thiscame at the cost of a high rate of severe infections in this particular group of heavily treated, frequentlysplenectomized, immunocompromised and fragile patients. Careful assessment of benefit/risk balance istherefore warranted before daratumumab administration."

Clinical • Congestive Heart Failure • Genetic Disorders • Heart Failure • Immune Thrombocytopenic Purpura • Immunology • Infectious Disease • Inflammatory Arthritis • Multiple Myeloma • Neutropenia • Otorhinolaryngology • Pneumonia • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Septic Shock • Thrombocytopenia • Thrombocytopenic Purpura

Real-world effectiveness and safety of fostamatinib in difficult-to-treat patients: Results of a three-year registry in France. (ASH 2025) - "Seventy-height percent ofpatients had been exposed to eltrombopag, 74.4% to romiplostim, 86.0% to rituximab, 48.8% tomycopenolate or azathioprine, and 28.0% were splenectomized. Fostamatinib was used in previously very heavily treated patients, with response rates of44.0% at M3 and of 20.0% at M24. Combination therapy with TPO-RA is an option to consider in thispopulation. No new safety signal was observed."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Hematological Malignancies • Immune Thrombocytopenic Purpura • Immunology • Infectious Disease • Lymphoma • Musculoskeletal Diseases • Myocardial Infarction • Neutropenia • Pulmonary Arterial Hypertension • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis

Efficacy of daratumumab in treatment of relapsed and/or refractory warm autoimmune hemolytic anemia in children (ASH 2025) - "Treatment options for steroiddependent, refractory/relapsed (r/r) wAIHA include rituximab, mycophenolate mofetil (MMF), and otherimmunosuppressants with splenectomy reserved for select cases...She was treated with steroids, rituximab, cyclosporine A (CSA), MMF, bortezomib,abatacept, sirolimus, and fostamatinib with multiple relpases...He was started on MMF anddaratumumab with remarkable recovery of hemolysis within 1 week; remains transfusion independent at1 month follow-up.Patient 4: A Caucasian girl diagnosed at 5 months of age with immunoglobulin G & complementmediated wAIHA initially responsive to prednisone and rituximab; she developed nephrotic syndromeand lupus nephritis by 1 year of age, complicated by renal failure. Multiple relapses of wAIHA weretreated with rituximab, cyclophosphamide, CSA, MMF, sirolimus, eculizumab, raviluzimab, andpegcetacoplan... In our experience daratumumab showed remarkable efficacy in treating r/r wAIHA inchildren. Responses were..."

Clinical • Anemia • Autoimmune Hemolytic Anemia • Glomerulonephritis • Hematological Disorders • Hematological Malignancies • Immune Thrombocytopenic Purpura • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Multiple Myeloma • Nephrology • Renal Disease • Thrombocytopenia • Thrombocytopenic Purpura

Fostamatinib significantly increases risk of hypertension in hematologic patients: A meta-analysis of randomized trials (ASH 2025) - "Fostamatinib use is associated with a 2.5-fold increased risk of developing hypertension. For patientswith hematologic conditions such as ITP, where chronic therapy is required, this adverse effect maycontribute to increased long-term cardiovascular and renal morbidity. We recommend routineambulatory blood pressure monitoring as per the AHA guidelines of maintaining a blood pressure goal ofless than 140 systolic and/or 90 diastolic as well as a goal of less than 130 systolic and/or 80 diastolic forcertain populations such as diabetes and early lifestyle or pharmacologic interventions to mitigate thisrisk."

Retrospective data • Autoimmune Hemolytic Anemia • Cardiovascular • Diabetes • Glomerulonephritis • Hematological Malignancies • Hypertension • IgA Nephropathy • Immune Thrombocytopenic Purpura • Immunology • Inflammatory Arthritis • Lupus • Metabolic Disorders • Renal Disease • Rheumatoid Arthritis • Systemic Lupus Erythematosus • Thrombocytopenic Purpura

Clinical and economic burden of steroids in primary immune thrombocytopenia: A real-world italian analysis (ASH 2025) - "Lately, subsequent therapies, including thrombopoietin receptor agonists,rituximab, and fostamatinib, have expanded the range of available options even in the early phases ofdisease. This analysis of the ITP population in real-world clinical practice in Italy revealed anassociation of CS treatment patterns with both the risk of chronic CSEs and healthcare costs. HD/HIsteroid therapy resulted in a significantly increased risk of chronic CSEs and a higher healthcare burdencompared to the LD/LI therapy. These findings underscore the limitations of prolonged or intensive CSuse in the management of ITP."

Clinical • HEOR • Real-world • Real-world evidence • Cardiovascular • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Infectious Disease • Thrombocytopenia • Thrombocytopenic Purpura • PER1

Trial in progress: Study design of a randomized, phase 3 trial evaluating the efficacy and safety of mezagitamab (TAK-079) compared with placebo in adults with chronic primary immune thrombocytopenia (ASH 2025) - P2, P3 | "Use of additional, stable Background ITPtherapy is permitted, including corticosteroids, thrombopoietin receptor agonists, and fostamatinib, as isuse of rescue therapy (corticosteroids, intravenous immunoglobulin, platelet transfusion) whenindicated. Given promising, early-stage results for anti-CD38 treatment in patients who have beendifficult to manage on current therapies, this global study will evaluate the efficacy and safety ofsubcutaneous mezagitamab as a potential novel therapy for patients with ITP who have had aninsufficient response or intolerance to prior therapy."

Clinical • P3 data • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura

Clinical characteristics, treatment strategies, and response patterns in evans syndrome: Initial analysis from the spanish resti cohort (ASH 2025) - "Cyclosporine was used in two patients with dual-lineage cytopenias,resulting in AIHA response in 41 days and neutrophil recovery in 15 days.Fostamatinib was used in four patients with concurrent ITP and AIHA...The median time from diagnosis to fostamatinib initiation was 531 days.All patients were on concomitant therapy (corticosteroids or avatrombopag)...This analysis from RESTI highlights the clinical heterogeneity and treatment challenges in Evanssyndrome. Corticosteroids remain first line of therapy but theyt are associated with incomplete ortransient responses in many patients. Rituximab demonstrated moderate efficacy across lineages, whilefostamatinib showed rapid, durable responses in both ITP and AIHA without observed toxicity, evenallowing treatment withdrawal in some cases."

Clinical • Autoimmune Hemolytic Anemia • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Neutropenia • Thrombocytopenia • Thrombocytopenic Purpura

Impact of treatment with fostamatinib on coagulation profile of patients with immune thrombocytopenia (ASH 2025) - "Fostamatinib treatment in ITP appears to reduce platelet apoptosis, which is associated with treatmentrefractoriness. The observed decrease in platelet apoptosis along with reduced fibrinogen receptoractivation and diminished thrombin generation, supports the favorable profile of fostamatinib in patientsat risk for thrombosis. To our knowledge, this is the first study to characterize the coagulation profile inpatients under fostamatinib therapy.This work was carried out with the support of project PI22/01489, funded by the Instituto de Salud CarlosIII (ISCIII) and co-funded by the European Union."

Clinical • Cardiovascular • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis • CASP8 • CD63 • SYK

Phase I trial of ruxolitinib plus fostamatinib for the treatment of steroid refractory chronic graft versus host disease (ASH 2025) - P1 | "Suboptimal response is defined as (1) cGVHDprogression after prednisone 1 mg/kg/d x 1 week, (2) cGVHD persistence despite prednisone 0.5 mg/kg/dx 4 weeks, (3) increase in prednisone dose to 0.25 mg/kg/d or higher after 1 unsuccessful taper attempt,(4) recurrence of cGVHD after attaining a CR with steroids, or (5) progression of cGVHD after attaining apartial response with steroids. Of note, prior treatment with ruxolitinibfor cGVHD for longer than 3 weeks is not permitted at this time, but there is a pending amendment topermit ruxolitinib use if longer than 6 months prior to enrollment and no prior severe toxicities. Priorruxolitinib use for acute GVHD is permitted."

P1 data • Acute Graft versus Host Disease • Cardiovascular • Chronic Graft versus Host Disease • Graft versus Host Disease • Hypertension • Immunology • SYK

Management of Autoimmune Hemolytic Anemia (ASH 2025) - "For relapsed/refractory patients rituximab has become the preferred second line-therapy, comparing favorably with the traditional splenectomy, which has been progressively abandoned or moved to further lines along with classic immunosuppressors. Several novel treatments are in development for wAIHA, encompassing drugs targeting B-cells (parsaclisib, ibrutinib, rilzabrutinib, zanubrutinib, obexelimab, ianalumab, povetacicept), plasma cells (bortezomib, daratumumab), spleen tyrosine kinase (fostamatinib, sovleplenib), and the neonatal Fc receptor (nipocalimab)."

IO biomarker • Anemia • Autoimmune Hemolytic Anemia • Bone Marrow Transplantation • Hematological Disorders • Immunology • Infectious Disease • HP • SYK

Construction of Metastasis Prediction Models and Screening of Anti-Metastatic Drugs Based on Pan-Cancer Single-Cell EMT Features. (PubMed, Int J Mol Sci) - "Moreover, elevated MPS and GMPS reflected immunosuppressive tumor microenvironment features and were significantly associated with poor prognosis across multiple cancer types. Finally, through a drug repositioning framework, we identified several potential anti-metastatic compounds targeting the metastasis network, among which Fostamatinib demonstrated broad-spectrum therapeutic potential against metastasis in multiple cancers."

Journal • Pan tumor • Oncology • CAFs

Fostamatinib (R788), a spleen tyrosine kinase inhibitor, sensitizes pancreatic cancer cells to oncolytic vesicular stomatitis virus. (PubMed, Mol Ther Oncol) - "Additionally, fostamatinib inhibited PDAC cell proliferation even in the absence of viral infection, while ruxolitinib did not. Our data suggest that fostamatinib may be repurposed as an effective drug that enhances OV therapy in PDAC by promoting OV replication and suppressing tumor growth."

Journal • Hematological Disorders • Immune Thrombocytopenic Purpura • Infectious Disease • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Thrombocytopenia • Thrombocytopenic Purpura • SYK

Immunotherapy-Associated Immune Thrombocytopenia: Treatment Paradigms (ASH 2023) - "We categorized patients into two cohorts: IO-ITP, those with a diagnosis of ITP after IO use (pembrolizumab, nivolumab, atezolizumab, avelumab, durvalumab, ipilimumab) and a diagnosis of neoplasm (ICD-10: C00-D49); and p-ITP: those with ITP without neoplasm nor IO use...We investigated the use of first-line and rescue therapies: glucocorticoids and IVIG; second-line therapies: thrombopoietin agonists (TPO-RAs: romiplostim and eltrombopag) and rituximab; third-line therapies: cyclophosphamide, azathioprine, cyclosporine, mycophenolate mofetil, bortezomib, avatrombopag and fostamatinib; and splenectomy, based on guidelines for management of p-ITP... Our study describes treatment patterns in IO-ITP, an uncommon but challenging disease. We found that individuals with IO-ITP are generally younger and predominantly male as compared to p-ITP, highlighting different patient profiles. We further demonstrated some distinctions in the management of these two conditions, possibly..."

Hematological Disorders • Immune Thrombocytopenic Purpura • Oncology • Skin Cancer • Thrombocytopenia • Thrombocytopenic Purpura

Management of autoimmune hemolytic anemia. (PubMed, Hematology Am Soc Hematol Educ Program) - "Rituximab is now the preferred second-line option for relapsed/refractory patients, comparing favorably with the traditional splenectomy. The latter is increasingly reserved for later lines together with classic immunosuppressants. Several novel treatments are in development for refractory wAIHA, encompassing drugs targeting B-cells (parsaclisib, ibrutinib, rilzabrutinib, zanubrutinib, obexelimab, ianalumab, povetacicept), plasma cells (bortezomib, daratumumab), spleen tyrosine kinase (fostamatinib, sovleplenib), and the neonatal Fc receptor (nipocalimab)."

Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Bone Marrow Transplantation • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Infectious Disease • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Transplantation • SYK

Using Fostamatinib to Treat Post-Hematopoietic Stem Cell Transplant Immune-mediated Cytopenias (clinicaltrials.gov) - P2 | N=1 | Terminated | Sponsor: National Heart, Lung, and Blood Institute (NHLBI) | Completed ➔ Terminated; Clinical trial was halted prematurely due to low enrollment

Trial termination • Anemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Immunology • Thrombocytopenia • Transplantation

Characterizing the Clinical, Humanistic, and Economic Burden of Warm Autoimmune Hemolytic Anemia: A Systematic Literature Review and Evidence Gap Assessment (ASH 2024) - "While there are no FDA-approved treatments specifically for wAIHA, treatments evaluated within the set of clinical trials included fostamatinib, rituximab, ibrutinib + rituximab, sovleplenib, parsaclisib, and pulse cyclophosphamide. While wAIHA is a relatively poorly studied disease, available data suggests low Hb levels and associated risks across both clinical trials and real-world study publications, reflecting a high unmet need in this patient population. Patient-reported outcomes, including health-related quality of life measures, should be evaluated with clinical outcomes in future trials and observational studies to facilitate understanding of outcomes that are important to patients."

Clinical • HEOR • Review • Anemia • Autoimmune Hemolytic Anemia • Fatigue • Hematological Disorders • Immunology

Clinical and Economic Burden of Illness in Patients with Persistent or Chronic Primary Immune Thrombocytopenia Treated with TPO-Ras and Rituximab (ASH 2023) - "Patients with ITP lasting for ≥3 months (persistent or chronic primary ITP), and who do not respond adequately or maintain a response to initial therapy, are usually treated with advanced therapies such as thrombopoietin receptor agonists (TPO-RAs [avatrombopag/romiplostim/eltrombopag]), rituximab, and fostamatinib. All-cause hospitalization was high in this population. Further studies are needed to understand long-term clinical and economic outcomes among ITP patients."

Clinical • HEOR • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Diabetes • Gastroenterology • Heart Failure • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Infectious Disease • Metabolic Disorders • Thrombocytopenia • Thrombocytopenic Purpura

Struck By Tsunami: Difficult Case of a Severe Refractory ITP (ASH 2024) - "While the majority of cases present with mild to moderate thrombocytopenia, severe cases can pose significant challenges in diagnosis and management.We present the case of a 65-year-old male with severe ITP refractory to initial standard treatment including steroids and intravenous immunoglobulin (IVIG) requiring further management including rituximab, romiplostim, Fostamatinib, romiplostim, Efgartigimoid alfa-fcab , eltrombopag and partial splenic embolization.Case presentationOur patient is a 65-year-old male with a significant medical history, including end-stage renal disease (ESRD), diffuse large B-cell lymphoma (DLBCL) status post-stem cell transplant in 2015, and chronic immune thrombocytopenic purpura (ITP)...Also during hospital stay General Surgery were consulted to assess the patient for splenectomy, which was deferred due to low platelet levels and to allow for further evaluation of the effects of embolization.Following two weeks from the second partial..."

Clinical • B Cell Lymphoma • Cardiovascular • Chronic Kidney Disease • Diffuse Large B Cell Lymphoma • Gastroenterology • Hematological Disorders • Hematological Malignancies • Immune Thrombocytopenic Purpura • Immunology • Infectious Disease • Lymphoma • Nephrology • Non-Hodgkin’s Lymphoma • Oncology • Renal Disease • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis

VAYHIT3: An Open-Label, Single-Arm, Phase II Trial to Evaluate the Efficacy and Safety of Ianalumab in Patients with Primary Immune Thrombocytopenia (ITP) Previously Treated with at Least 1 Corticosteroid and 1 Thrombopoietin Receptor Agonist (TPO-RA) (ASH 2023) - P2, P3 | "For patients who previously received corticosteroids and a TPO-RA, the choice of subsequent therapy (eg a different TPO-RA, rituximab, fostamatinib, mycophenolate mofetil, splenectomy) is not well defined. VAYHIT3 will evaluate the ability of a short therapeutic course of ianalumab to induce durable responses in patients who have received 2 or more prior lines of therapy, including at least 1 corticosteroid and 1 TPO-RA, for whom significant unmet needs exist. Current status: VAYHIT3 is recruiting. Ianalumab is also being investigated in 2 ongoing, randomized, double-blind, Phase III ITP trials: VAYHIT1 (NCT05653349) is assessing ianalumab versus placebo in addition to first-line corticosteroids, and VAYHIT2 (NCT05653219) is assessing ianalumab versus placebo in addition to eltrombopag in patients who failed first-line corticosteroid treatment."

Clinical • P2 data • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura