Treatment-free remission (TFR) is an emerging goal for patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKI). However, long-term TFR durability in real-world settings remains understudied. The J-SKI study, a large observational study, was conducted to evaluate long-term TFR outcomes in Japanese patients with CML. This interim analysis included 795 eligible patients from the prospective (n = 283) and retrospective (n = 512) cohorts. With a median follow-up of 32 months (range 0.8–168) after TKI discontinuation, the 5-year TFR rate was 65.2

Prognostic factors for long-term survival (LTS), defined as overall survival (OS) of ≥10 years, remain uncertain among patients with myeloma who undergo autologous stem cell transplantation (ASCT). We retrospectively analyzed 3650 patients with myeloma who underwent ASCT between 1994 and 2013 using the Japanese Society of Transplantation and Cellular Therapy registry. The proportion of long-term survivors was 28.7%. In logistic regression analyses, IgG-type, absence of high-risk cytogenetic abnormality (HRCA), International Staging System (ISS) I/II, and post-transplantation therapy were associated with LTS. Cox regression analysis revealed that kappa light chain type and post-transplantation therapy predicted better OS, whereas PS 2-4, HRCA, melphalan dose under 200 mg/m2, and ISS III predicted a shorter OS. We classified patients into three groups on the six significant factors; the estimated 10-year OS among the favorable group was 60.9%. ISS, HRCA, M-protein subtype, melphalan dose, achieving CR, and post-transplantation therapy were associated with LTS after ASCT.

Differentiation syndrome (DS) is rarely observed before treatment in patients with acute promyelocytic leukemia (APL). A 35-year-old man with high-risk APL and influenza A presented with multiple organ failure (MOF). Initially attributed to influenza, the DS-like symptoms rapidly worsened after the initiation of all-trans retinoic acid. Despite intensive care and continuous hemodialysis, the patient developed a cerebral hemorrhage. Consequently, dose-adjusted arsenic trioxide (ATO; 0.1 mg/kg/day) was administered. He achieved complete remission (CR) on day 28 and maintained molecular CR for 16 months without sequelae. Concurrent infections can mask DS-like symptoms prior to treatment. Reduced-dose ATO is an effective salvage option for patients with APL and severe MOF.

Wilms tumor gene 1 (WT1) is frequently identified in hematologic malignancies; however, its utility for measurable residual disease (MRD) assessment remains controversial. We investigated the prognostic impact of WT1 dynamics in peripheral blood (PB) before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Of 85 patients with AML or MDS who underwent allo-HSCT at our institution between January 2016 and March 2025, 51 who had WT1 in PB assessed before and approximately 100 days after transplantation were analyzed retrospectively. Patients were stratified by WT1 status before and/or after allo-HSCT. WT1 expression < 50 copies/µg RNA was defined as MRD-negative. In univariate analysis, 2-year progression-free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR) differed significantly between Group A (MRD−/MRD−), Group B (MRD+/MRD−), and Group C (MRD+/MRD+) (PFS: 93.8

A 31-year-old female presented at our hospital with fatigue and subcutaneous bleeding. Blood tests revealed hemolytic anemia. The patient had Coombs-negative normocytic anemia and thrombocytopenia; therefore, thrombotic thrombocytopenic purpura was ruled out. On day two, we noticed that the eating habits of the patient, hypersegmented neutrophils, and megaloblastic changes suggested malnutrition; therefore, we initiated vitamin supplementation. On day six, the vitamin C levels were <0.2 μg/mL, and the patient was therefore diagnosed with scurvy. Scurvy can mimic hemolytic anemia by causing normocytic megaloblastic anemia with a high reticulocyte count. Hypersegmented neutrophils and a detailed medical history are important for making a differential diagnosis.

BackgroundAlthough the Omicron variant has been reported to reduce COVID-19 severity in the general population, its impact on patients with hematologic malignancies remains uncertain, and epidemiological investigation is warranted.MethodsWe conducted a multicenter retrospective cohort study of 1, 023 patients with hematologic diseases diagnosed with COVID-19 at 22 centers in Japan between January 2020 and January 2023. Outcomes within 60 days after diagnosis including severe and/or prolonged disease, COVID-19–related mortality, and overall survival (OS) were compared between the pre-Omicron and Omicron periods. Multivariable analysis was performed to identify independent adverse prognostic factors.ResultsSevere and/or prolonged disease occurred in 27.5% of patients, COVID-19–related mortality was 6.3%, and OS was 91.4%. Compared with the pre-Omicron period, the Omicron period was associated with significantly lower rates of severe/prolonged disease (26.0% vs. 48.0%, P<0.01) and COVID-19–related mortality (5.0% vs. 15.0%, P<0.01), but no significant difference in OS (92.0% vs. 84.0%, P = 0.62). Age ≥60 years was the strongest predictor of severe/prolonged disease (sHR 3.08, P<0.01) and mortality (HR 8.94, P<0.01). Male sex (sHR 1.38; HR 1.82, both P<0.01) and prior bendamustine exposure (sHR 1.83; HR 1.87, both P<0.01) were also associated with both outcomes, whereas anti-CD38 antibody therapy was linked only to mortality (HR 3.65, P<0.01).ConclusionIn patients with hematologic diseases, the Omicron period was associated with reduced severity and COVID-19–related mortality but no improvement in OS. Older age and prior bendamustine exposure were strongly associated with adverse outcomes, highlighting the need for strict infection prevention and prompt, aggressive COVID-19 management in these high-risk populations.

This study compared dasatinib and imatinib in adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). Using pooled data from three JALSG prospective trials (Ph + ALL202, Ph + ALL208, Ph + ALL213), we analyzed outcomes for 206 patients aged 15–64 years treated with dasatinib (n = 74) or imatinib (n = 132) in combination with chemotherapy. We applied propensity score matching (1:1) and inverse probability of treatment weighting to minimize selection bias and balance baseline characteristics. Dasatinib plus chemotherapy was associated with significantly higher complete molecular response rates after induction therapy compared with imatinib. In the propensity score-matched cohort (n = 68 patients per group), 3-year event-free survival (EFS) was significantly higher with dasatinib (73 vs. 49

Abstract Introduction: Tyrosine Kinase Inhibitors (TKIs) have substantially improved survival outcomes for patients with chronic myeloid leukemia in chronic phase (CML-CP). In clinical practice, however, TKI treatment has generally been considered a life-long commitment. Several clinical trials, including the largest prospective study, the EURO-SKI trial, have demonstrated that TKI therapy can be safely discontinued in approximately half of the patients who achieve and maintain a deep molecular response (DMR). Although a subset of Japanese patients treated with TKIs achieves sustained DMR and may be eligible for Treatment-Free Remission (TFR), the long-term durability of TFR in a real-world setting remains unclear. Furthermore, the clinical and biological factors predicting successful TKI discontinuation are not fully elucidated, and little is known about the outcomes of a second TFR attempt. Objectives: The primary objective of this study was to determine the long-term TFR rate after TKI discontinuation in a large, real-world cohort of Japanese patients. The primary endpoint was the TFR rate at 5 years. Secondary endpoints included treatment-free survival (TFS), progression-free survival, and the cumulative incidence of regaining major molecular response (MMR) after treatment resumption. Exploratory endpoints were the identification of predictive factors for successful TFR and the success rate of a second TFR attempt. Methods: J-SKI is a multicenter observational study comprising two cohorts: a prospective TFR cohort of patients who newly discontinued TKI therapy in routine practice according to the 2018 JSH guidelines, and a retrospective TFR cohort of patients who had previously discontinued TKIs and were subsequently followed prospectively. Patients with major BCR::ABL1 positive CML were enrolled from September 2019 to March 2025, with a data cut-off date of May 31, 2024. All participants provided written informed consent. Key exclusion criteria included the inability to provide clinical information per the study schedule or participation in another clinical study where data submission to this registry was not permitted. Results: Of 844 patients registered, 795 were eligible for time-to-event analysis (Prospective cohort, n=283; Retrospective cohort, n=512). At data cut-off, 302 patients were evaluable for the 60-month primary endpoint. The overall TFR rate at 60 months was 65.2% (95% CI: 59.6-70.6%). Of the patients who experienced molecular relapse and resumed TKI therapy, 87% (95% CI: 82-92%) subsequently regained MMR. No patients progressed to blast crisis. A multivariate Cox regression analysis identified a longer duration of MR4.5 as the sole independent predictor for successful TFR (HR: 0.875; 95% CI: 0.829–0.924; p < 0.0001), corresponding to a 12.5% relative reduction in the risk of molecular relapse for each additional year of MR4.5. Furthermore, sustained MR4.5 at 1 or 3 months after TKI discontinuation was significantly associated with superior TFS compared to loss of MR 4.5 (p<0.0001, Log-rank test). A second TFR attempt was performed in 32 patients who failed their first attempt, with a subsequent TFS rate of approximately 40%. Conclusion: This 5-year interim analysis of the J-SKI study demonstrates that TKI discontinuation is a safe and feasible strategy for Japanese patients with CML in a real-world setting. These data support TFR as an achievable therapeutic goal in routine clinical practice, provided that established discontinuation criteria are met. As the duration of DMR is a key independent predictor for TFR success, future strategies should focus on methods to achieve and maintain DMR early in the treatment course. Our findings also suggest that a second TFR attempt can be a viable option for select patients.

BACKGROUND AIMS:Antithymocyte globulin (ATG) has been used to prevent the incidence of graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Low-dose ATG can suppress GVHD without increasing the risk of infectious complications. However, the relationship between ATG exposure and transplant outcomes in low-dose settings remains unclear, particularly in terms of the effect of absolute lymphocyte count (ALC) on its pharmacokinetics. This study aimed to explore the relationship between ATG exposure and transplant outcomes, with a focus on immune reconstitution and GVHD prevention, and to examine whether the pre-ATG ALC could predict ATG exposure in the low-dose setting. METHODS:This prospective, multicenter, observational study included 71 patients with hematologic malignancies who underwent peripheral blood stem cell transplantation at six centers between May 2019 and March 2023. The serum concentration of ATG was measured over time. The area under the curve (AUC) was determined, and the correlations with the incidence of GVHD, post-transplant immune recovery, and survival were examined. RESULTS:Fifty-three of the 71 patients received ATG; the remaining 18 did not. Three distinct patterns of ATG administration were observed: standard (total 2.5 mg/kg: 1.25 mg/kg administered on days-2 and -1), early standard (total 2.5 mg/kg administered before day-2), and early reduced (total 1.25 mg/kg: single dose administered before day-2). Successful immune reconstitution (CD4 ≥ 120/μL at day 60) exhibited correlations with improved relapse-free survival (78.9% vs 47.7%, P = 0.034) and lower relapse rates (4.9% vs 37.2%, P = 0.003). Lower post-transplant AUC (≤ 250 μg/mL/day) exhibited an independent association with successful immune reconstitution (OR = 6.59 [95% CI, 1.23-35.40], P = 0.028). The post-transplant ATG exposure in the early reduced group was lower than those in the standard (P < 0.001) and early standard groups (P = 0.004). The ATG/ALC ratio was strongly correlated with the post-transplant AUC in the early administration groups (Spearman's correlation coefficient = 0.71, P < 0.001). The incidences of grade II-IV acute GVHD (17.1% vs. 39.4%, P = 0.013) and moderate-to-severe chronic GVHD (19.6% vs. 49.4%, P = 0.029) were significantly lower in the ATG group compared to the non-ATG group. The administration methods and ATG exposure levels had no effect on the incidence of GVHD in the ATG group. CONCLUSIONS:Early administration of reduced-dose ATG prevents the incidence of GVHD; furthermore, it potentially optimizes immune reconstitution by lowering post-transplant ATG exposure. The strong correlation between pre-ATG ALC and ATG exposure indicates that ALC-based dosing strategies may be beneficial even in low-dose settings. The ATG/ALC ratio is a practical tool for individualizing ATG dosing during early administration.

Background:Interleukin (IL)-6 is associated with wound healing and infection response. Tocilizumab (TCZ) is a monoclonal antibody against the IL-6 receptor, interfering with its signalling pathway. However, reports on patients treated with TCZ undergoing cardiac surgery are limited. Case summary:A 73-year-old man with Castleman disease, treated with TCZ, underwent surgical aortic valve replacement via median sternotomy for aortic valve regurgitation with exertional shortness of breath. Comprehensive measures for preventing surgical site infection along with close examination were implemented during the perioperative period. Tocilizumab was discontinued 26 days before surgery and resumed 30 days after surgery, during which plasma IL-6 levels decreased. There was no evidence of infection or exacerbation of Castleman disease. Vascular endothelial growth factor levels increased before an increase in C-reactive protein levels following hospital discharge and prior to TCZ resumption. Discussion:Meticulous perioperative management with a multi-disciplinary approach is crucial during the cessation of TCZ for cardiac surgery. Changes in vascular endothelial growth factor levels may serve as an early predictor of underlying disease exacerbation after TCZ cessation for surgery.

Zanubrutinib is a selective second-generation Bruton tyrosine kinase inhibitor approved in various B-cell malignancies globally. The phase 1/2 BGB-3111-111 study evaluated the efficacy and safety of zanubrutinib 160 mg twice daily orally in Japanese patients with treatment-naive or relapsed/refractory mature B-cell malignancies. Here, efficacy results from Part 2 in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; n = 19) and Waldenström macroglobulinemia (WM; n = 19), and safety results from Parts 1 (N = 6) and 2 (N = 49) are presented, with the first dose between 30 January, 2020, and 31 October, 2022. As of 10 May, 2023, investigator-assessed overall response rates were 100

Post-transplant tyrosine kinase inhibitors (TKIs) show promise in preventing relapse after allogeneic hematopoietic cell transplantation (allo-HCT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). However, their real-world use and efficacy remain unclear. A comprehensive study across seven centers included Ph+ALL patients who underwent allo-HCT between 2002 and 2022. Post-transplant TKIs were administered in 28

A 42-year-old woman was diagnosed with monomorphic epithelial-type intestinal T-cell lymphoma (MEITL) following small bowel endoscopy. The patient subsequently underwent a small bowel resection to prevent perforation. Bowel lesions progressed shortly after completion of first-line chemotherapy. Although four different salvage regimens were attempted, they were refractory, and both bowel and ovarian lesions progressed. Partial jejunal resection was performed during the fifth salvage regimen, followed by oophorectomy. After achieving complete remission, she underwent cord blood transplantation and remained alive 37 months after the diagnosis. Integration of elective surgery and allogeneic transplantation may be a treatment option for relapsed or refractory MEITL.

Background: The clinical application of FLT3 inhibitors has improved the prognosis of AML with FLT3 mutation, but the short duration of response to FLT3 inhibitors and the emergence of resistant clones remain challenges. The mechanisms of FLT3 inhibitor resistance can be divided into two categories: cellular intrinsic factors such as acquisition of resistance gene mutations, and extracellular factors, such as FLT3 ligand (FL) stimulation. Particularly, the attenuated inhibitory effect of FLT3 inhibitors through the activation of wild-type FLT3 which is co-expressed in the most of AML cells by FL stimulation needs to be clarified in clinical practice. In this study, we aimed to elucidate the factors affecting gilteritinib efficacy and the mechanisms of resistance using patient samples. Methods: This study included patients 16 years of age or older with relapsed or refractory AML with FLT3 mutation, and who were scheduled to receive gilteritinib. Clinical information, patient plasma, and AML cells from bone marrow or peripheral blood were collected over time. FL concentrations were measured at the points defined in the study plan and plasma inhibitory activity assay (PIA) assay was performed using 32D cells co-expressing wild-type FLT3 and ITD-FLT3. Targeted sequencing was performed on samples collected at study enrollment and at relapse or refractory stage. Primary endpoint was the association between PIA assay and best clinical response. Secondary endpoints were the relation between the clinical response to gilteritinib and the gene mutation profiles. Results: 30 patients (15 males and 15 females) were enrolled from April 14, 2020, to December 20, 2022. Median patient age was 68 years. (range 34-84). Median observation period was 815 days (range 193-1173). 26 of the 30 patients were positive for FLT3-ITD mutation and five for TKD mutation with one patient carrying both mutations. Of the 30 patients, 18 had received no chemotherapy within four weeks prior to gilteritinib except for hydroxyurea. Eight received intensive chemotherapy within 15 days, and four were treated with other therapies prior to gilteritinib. The composite complete remission (CRc) rate for all patients was 50%, median overall survival was 250 days and median progression-free survival was 170 days. Coexisting genetic mutations frequently identified were NPM1 (47%), DNMT3A (40%), RUNX1 (17%), TET2 (17%), IDH2 (13%), CEBPA (10%), U2AF1 (10%), and WT1 (10%) mutations, however, there was no correlation with prognosis. The median plasma FL concentration at the initiation of treatment was 0 pg/ml (range 0-199), and patients who reached CRc in the patients with no prior intensive chemotherapy within 4 weeks showed a gradual increase in FL concentration, which was significantly higher at day 29 compared to patients who did not achieve CRc (median 240 pg/ml vs 45 pg/ml, P=0.017).The inhibitory level of FLT3 phosphorylation in PIA assay using plasma on Day 29 of gilteritinib treatment did not correlate with best response in patients with or without CRc achievement. However, patients in prior intensive chemotherapy group showed a significant rapid increase in plasma FL levels on days 4 to 29 after initiation of gilteritinib compared to those in the no prior treatment group, and a decrease in FLT3 phosphorylation inhibitory activity from Day 4 to Day 15 by PIA assay. Of 18 patients with refractory or relapsed disease after gilteritinib treatment, 6 patients were found to be FLT3 mutation negative, and 6 patients had acquired mutations involved in activation of RAS/MAPK pathway. Conclusion: No correlation was found between the best clinical response and inhibition level of FLT3 phosphorylation in PIA assay at day 29 of gilteritinib monotherapy. In this study, there was no relation between treatment response and on- or off-target resistance mechanisms, suggesting the involvement of multiple factors such as activation of pathways implicated in other drug susceptibilities. In the group of patients who received prior potent chemotherapy within two weeks, there was a rapid increase in plasma FL concentration and a decrease in FLT3 inhibitory activity in PIA assay. In combination of chemotherapy and FLT3 inhibitor, the increase in FL concentration due to chemotherapy and the possibility of decreased inhibitory activity of FLT3 inhibitors during the period of increased FL concentration in AML cells co-expressing wild-type FLT3 should be considered.

The emergence of novel drugs has significantly improved outcomes of patients with plasma cell neoplasms (PCN). The Japanese Society of Hematology conducted a prospective observational study in newly diagnosed PCN patients between 2016 and 2021. The analysis focused on 1385 patients diagnosed with symptomatic PCN between 2016 and 2018. The primary endpoint was the 3-year overall survival (OS) rate among patients requiring treatment (n = 1284), which was 70.0% (95%CI 67.4-72.6%). Approximately 94% of these patients received novel drugs as frontline therapy. The 3-year OS rate was 90.3% (95%CI 86.6-93.1%) in the 25% of patients who received upfront autologous stem cell transplantation (ASCT), versus just 61.4% (95%CI 58.0-64.6%) in those who did not receive upfront ASCT. The only unfavorable prognostic factor that affected OS in ASCT recipients was an age of 65 or higher. For patients who did not receive ASCT, independent unfavorable prognostic factors included frontline treatment with conventional chemotherapies, international staging system score of 2/3, extramedullary tumors, and Freiberg comorbidity index of 2/3. This study unequivocally demonstrates that use of novel drugs improved OS in Japanese myeloma patients, and underscores the continued importance of upfront ASCT as the standard of care in the era of novel drugs.

This study aimed to investigate the usefulness of allogeneic stem cell transplantation (allo-SCT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) in the first complete remission (CR1) with complete molecular remission (CMR). We compared the outcomes between Ph+ALL patients who did or did not undergo allo-SCT in CR1. We included patients enrolled in the prospective clinical studies in the tyrosine kinase inhibitor era conducted by the Japan Adult Leukemia Study Group, who achieved CMR within 3 months. A total of 147 patients (allo-SCT: 101; non-SCT: 46) were eligible for this analysis. In the multivariate analyses, allo-SCT was significantly associated with both superior overall survival (OS) (adjusted hazard ratio (aHR): 0.54; 95% CI: 0.30-0.97; p = .04) and relapse-free survival (RFS) (aHR: 0.21; 95% CI: 0.12-0.38; p < .001). The 5-year adjusted OS and RFS were 73% and 70% in the allo-SCT cohort, whereas they were 50% and 20% in the non-SCT cohort. Despite the higher non-relapse mortality (aHR: 3.49; 95% CI: 1.17-10.4; p = .03), allo-SCT was significantly associated with a lower relapse rate (aHR: 0.10; 95% CI: 0.05-0.20; p < .001). In addition, allo-SCT was also associated with superior graft-versus-host disease-free, relapse-free survival (aHR: 0.43; 95% CI: 0.25-0.74; p = .002). Propensity score-matched analyses confirmed the results of the multivariate analyses. In patients who achieved CMR within 3 months, allo-SCT in CR1 had superior survival and lower relapse compared with the non-SCT cohort.

In Waldenström macroglobulinemia (WM), confirming the presence of Bing-Neel syndrome (BNS) is important because drugs that penetrate the central nervous system (CNS) must be selected. We report the case of a 75-year-old man for whom tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor (BTKi), was useful in treating WM-associated peripheral neuropathy (PN) with BNS. Numbness and muscle weakness in the fingers occurred three years after the initial treatment of WM. WM-associated PN due to demyelinating disease was diagnosed based on the results of a nerve conduction study and magnetic resonance imaging showing bilateral symmetric swelling of the brachial plexus. The cerebrospinal fluid (CSF) cytology results were initially negative; however, the CSF test was repeated because of extremely high protein levels (984 mg/dL) and slightly elevated leukocyte counts (14/µL). The second test revealed abnormal lymphoplasmacytic cells (189/µL), indicating BNS. Rituximab and high-dose methotrexate-containing chemotherapy were administered. Despite the subsequent negative CSF cytology results, his neurological symptoms persisted but subsided soon after the initiation of tirabrutinib. The therapeutic effects of tirabrutinib persisted for 25 months. This case suggested that a careful search for concurrent BNS is important when lesions are close to the CNS or when atypical CSF findings are obtained in patients with WM-associated PN, especially when BTKi options are available.

Ibrutinib is a first-in-class Bruton’s tyrosine kinase inhibitor that is approved for the treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in Japan based on randomized clinical trial data. The aim of the real-world, retrospective Orbit study was to describe long-term clinical outcomes and management in adults (aged ≥ 20 years) with CLL/SLL treated with ibrutinib, either as first-line (1L) treatment or for relapsed or refractory (RR) disease, in routine clinical practice in Japan between July 2018 and December 2020. A total of 246 patients were registered, and the safety and per-protocol sets included 237 and 234 patients, respectively. After a median follow-up of 35.7 months, the 36-month progression-free survival rate was 80.9

Background Fostamatinib, a spleen tyrosine kinase inhibitor, has been approved for the treatment of chronic immune thrombocytopenia (ITP) in adults in the US, Canada, Europe, Israel, and Japan. We evaluated the long-term efficacy and safety of fostamatinib treatment and the off-therapy platelet count in Japanese patients with primary ITP in a phase 3 clinical trial with a 24-week double-blind period, a 28-week open-label extension period, and a pre-defined washout period. Methods The trial enrolled Japanese patients who had failed to respond or did not tolerate ≥1 prior ITP treatment, who had a mean platelet count <30,000/μL (based on 3 screening and baseline platelet measurements), and had a platelet count at each visit <35,000/μL. Dosing was at 100 mg bid for 4 weeks and then 150 mg bid if needed and tolerated. One concomitant treatment was allowed (corticosteroids, azathioprine or danazol). The dosage of the concomitant treatment was to remain the same during the 24-week double-blind period but could be reduced or discontinued during the open-label period. Efficacy endpoints were platelet response rate (i.e., the percentage of patients who achieved a platelet count of ≥ 50 × 10 3/μL at 2 consecutive visits at least 28 days apart). The platelet count of the responders during the study period were evaluated. Results A total of 33 patients who were either treated with fostamatinib in the 24-week double-blind period (Fostamatinib-Fostamatinib group, n=22) or treated with placebo in the double-blind period and then treated with fostamatinib in the 28-week open-label extension period (Placebo-Fostamatinib group, n=11) were analyzed. Of those, 79% (26/33) were women, the median age was 62, the median baseline platelet count was 19 x 10 3/μL, and 58% (19/33) had two or more previous treatments. The platelet response rate was 36% (8/22) in the Fostamatinib-Fostamatinib group and 27% (3/11) in the Placebo-Fostamatinib group. The platelet count of the responders in the Fostamatinib-Fostamatinib group increased to ≥50 × 10 3/μL shortly after initiating fostamatinib and remained around 100 × 10 3/μL between Week 14 and Week 52, whereas the platelet count of the responders in the Placebo-Fostamatinib group remained low while receiving placebo but increased after receiving fostamatinib ( Figure 1). Among 14 patients with concomitant glucocorticoids treatments at the beginning of the open-label period, 43% (6/14) reduced or discontinued glucocorticoids while receiving fostamatinib without disease relapse. In the washout period of up to 4 weeks, all 12 patients experienced a mild decrease in platelet count, but none developed bleeding events ( Figure 2). Three of four patients who completed the 4-week washout period had a slight increase in platelet counts from Week 2 to Week 4. In the double-blind and open-label periods, adverse events were reported in 96% (21/22) of the Fostamatinib-Fostamatinib group and 100% (11/11) of the Placebo-Fostamatinib group, and treatment-related adverse events in 77% (17/22) and 46% (5/11), respectively. In the washout period, adverse events were reported in 50% (6/12) of patients, and treatment-related adverse events in 0% (0/12). We found no new safety risk or late-onset adverse events specific to Japanese patients. Conclusions The long-term efficacy and safety of fostamatinib were observed in Japanese patients with primary ITP, along with the feasibility of glucocorticoid reduction/discontinuation during fostamatinib treatment, and a lack of bleeding events after abrupt discontinuation of fostamatinib. The findings obtained from this study will help position fostamatinib as a second-line treatment in patients with primary ITP.