Avatrombopag as alternative therapy for severe aplastic anemia patients who are intolerant or unresponsive to eltrombopag.

Introduction: Eltrombopag (EPAG), a thrombopoietin receptor agonist, was approved for the treatment of severe aplastic anemia (SAA) combined with immunosuppressive therapy (IST). However, EPAG contains a typical biphenyl structure, which causes liver function damage. Methods: Twenty patients with SAA who were intolerant or refractory to EPAG were enrolled in a multicenter prospective registry of the Chinese Eastern Collaboration Group of Anemia (ChiCTR2100045895) from October 2020 to June 2023. Results: Eight patients who were ineffective to EPAG, six with kidney impairment, and nine with abnormal liver function (two with concomitant liver and kidney impairment) were converted to avatrombopag (AVA) therapy with the median duration of AVA treatment was 6 (3-24) months. 17 cases (85%) achieved trilineage hematological response (HR): complete remission (CR) in 3 cases (15%), good partial remission (GPR) in 4 cases (20%), partial remission (PR) in 10 cases (50%), and no response (NR) in 3 cases (15%). The median time to response was 1.7 (0.5-6.9) months, with 16 cases (94%) achieving response within six months and 17 cases (100%) within 12 months. 9 cases (50%) achieved transfusion independence. AVA converted treatment was associated with higher neutrophil counts (0.8×109/L vs 2.2×109/L, p=0.0003), platelet counts (11×109/L vs 39×109/L, p=0.0008), hemoglobin count (59g/L vs 98g/L, p=0.0002), red cell count (1.06×1012/L vs 2.97×1012/L, p=0.001), and absolute reticulocyte count (31.99 ×109/L vs 67.05×109/L p=0.0004) were all significantly elevated compared with the pre-treatment level. After the conversion to AVA therapy, liver and kidney function indexes were maintained within the normal range, no AVA related grade 2 or higher adverse events occurred, and no thrombotic events occurred. Conclusion: The conversion to AVA was an optimal choice for patients with SAA who were EPAG intolerant or refractory. Clinical trial registration: http://www.chictr.org.cn/showproj.html?proj=125480, identifier ChiCTR2100045895.

Refractory pure red cell aplasia associated with T-cell large granular lymphocyte leukemia treated by ruxolitinib.

Acquired pure red cell aplasia (PRCA) is a rare syndrome characterized by normocytic normochromic anemia with severe reticulocytopenia and absence of erythroid precursors in the bone marrow. For refractory PRCA patients, the low response rate and high toxicity of alternative therapies pose a great challenge. T-cell large granular lymphocyte (T-LGL) leukemia is one of the most common conditions in secondary PRCA and also the most difficult form to manage with an inferior treatment response to other secondary PRCA forms. T-LGL leukemia exhibits sustained activation of the intracellular JAK-STAT signaling pathway. We herein report a case of PRCA associated with T-LGL leukemia that had been refractory to multiple lines of therapies and was successfully treated by ruxolitinib. The patient achieved complete remission and tolerated ruxolitinib well without occurrence of neutropenia or thrombocytopenia. This preliminary finding favors ruxolitinib as a potential salvage therapy for refractory PRCA associated with T-LGL leukemia.

Phase 3 randomized COMMODORE 2 trial: Crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria naive to complement inhibition.

Crovalimab is a novel C5 complement inhibitor that enables rapid and sustained C5 inhibition with subcutaneous, low-volume self-administration every 4 weeks. COMMODORE 2 (NCT04434092) is a global, randomized, open-label, multicenter, phase 3 trial evaluating the non-inferiority of crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria not previously treated with C5 inhibition. C5 inhibitor-naive patients with lactate dehydrogenase (LDH) ≥2 × upper limit of normal (ULN) were randomized 2:1 to crovalimab or eculizumab. Co-primary efficacy endpoints were proportion of patients with hemolysis control (centrally assessed LDH ≤1.5 × ULN) and proportion with transfusion avoidance. Secondary efficacy endpoints were proportions of patients with breakthrough hemolysis, stabilized hemoglobin, and change in FACIT-Fatigue score. The primary treatment period was 24 weeks. Two hundred and four patients were randomized (135 crovalimab; 69 eculizumab). Crovalimab was non-inferior to eculizumab in the co-primary endpoints of hemolysis control (79.3% vs. 79.0%; odds ratio, 1.0 [95% CI, 0.6, 1.8]) and transfusion avoidance (65.7% vs. 68.1%; weighted difference, -2.8 [-15.7, 11.1]), and in the secondary efficacy endpoints of breakthrough hemolysis (10.4% vs. 14.5%; weighted difference, -3.9 [-14.8, 5.3]) and hemoglobin stabilization (63.4% vs. 60.9%; weighted difference, 2.2 [-11.4, 16.3]). A clinically meaningful improvement in FACIT-Fatigue score occurred in both arms. Complete terminal complement activity inhibition was generally maintained with crovalimab. The safety profiles of crovalimab and eculizumab were similar with no meningococcal infections. Most patients who switched from eculizumab to crovalimab after the primary treatment period preferred crovalimab. These data demonstrate the positive benefit-risk profile of crovalimab.

Efficacy and safety of eltrombopag in Chinese patients with refractory or relapsed severe aplastic anemia.

For patients with severe aplastic anemia (SAA) in China who have had an insufficient response to the first-line treatment with hematopoietic stem cell transplantation or immunosuppressive therapy, there is no established standard of care other than transfusion support and treatment of infections. This non-randomized, open-label, Phase II multicenter trial investigated the efficacy and safety of eltrombopag in 20 adult Chinese patients with refractory or relapsed (r/r) SAA. The primary endpoint of hematologic response rate at Week 26, defined as the proportion of patients who met any of the International Working Group criteria, was observed in 70% (14/20) of patients, with more than 50% of these having at least bi-lineage response. Reduced red blood cell and platelet transfusion at Week 26 were observed in 57% (8/14) and 80% (8/10) of patients, respectively. Safety findings were consistent with the established safety profile of eltrombopag and no new safety signals were reported. None of the patients discontinued eltrombopag because of safety concerns. Although the sample size was small, this is the first prospective study to show that eltrombopag is efficacious and has a favorable safety profile in a Chinese patient population with r/r SAA.Trial registration: This trial is registered on ClinicalTrials.gov (NCT03988608); registered 17 June 2019.

Severe hemolytic exacerbations of Chinese PNH patients infected SARS-CoV-2 Omicron.

INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by hemolytic anemia, bone marrow failure, thrombophilia. COVID-19, caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with many variants including Omicron. METHODS: This study collected demographic and clinical data of 20 PNH patients with SARS-CoV-2 Omicron infection. RESULTS: They all were with high disease activity, and LDH level exceeded any documented since the diagnosis of PNH, and those reported in the literature for previously stable treatment with complement inhibitors. D-dimer level elevated in 10 patients. 2 patients developed mild pulmonary artery hypertension. Glomerular filtration rate declined in 5 patients. 1 patient developed acute renal failure and underwent hemodialysis. Anemia and hemolysis were improved in 5 patients treated with eculizumab. CONCLUSIONS: Hemolytic exacerbation of PNH with COVID-19 is severe and eculizumab may be an effective treatment.

Safety and efficacy of jaktinib (a novel JAK inhibitor) in patients with myelofibrosis who are intolerant to ruxolitinib: A single-arm, open-label, phase 2, multicenter study.

Although ruxolitinib improves splenomegaly and constitutional symptoms in patients with myelofibrosis (MF), a substantial proportion of patients discontinue ruxolitinib because of intolerance. This phase 2 trial investigated the safety and efficacy of jaktinib, a novel JAK inhibitor in patients with ruxolitinib-intolerant MF. The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) at week 24. The secondary endpoints included change of MF-related symptoms, anemic response, and safety profiles. Between December 18, 2019, and November 24, 2021, 51 patients were enrolled, 45 treated with jaktinib 100 mg bid (100 mg bid group) and six received non-100 mg bid doses (non-100 mg bid group). The SVR35 at week 24 in the 100 mg bid group was 43.2% (19/44, 95% CI 29.7%-57.8%). There were 41.9% (13/31) of transfusion-independent patients with hemoglobin (HGB) ≤100 g/L who had HGB elevation ≥20 g/L within 24 weeks. The proportion of patients with a ≥50% decrease in the total symptom score (TSS 50) at week 24 was 61.8% (21/34). The most commonly reported grade ≥3 treatment-emergent adverse events (TEAEs) in the 100 mg bid group were anemia 31.1%, thrombocytopenia 22.2%, and infectious pneumonia 17.8%. A total of 16 (35.6%) in the 100 mg bid group had serious adverse events, and 4 (8.9%) were considered possibly drug related. These results indicate jaktinib can provide a treatment option for patients with MF who are intolerant to ruxolitinib.

Transfusion-dependent non-severe aplastic anemia: characteristics and outcomes in the clinic.

Transfusion-dependent non-severe aplastic anemia (TD-NSAA) is a rare condition of bone marrow failure that can persist for a long time or develop into severe aplastic anemia (SAA). Little is known about the clinical and laboratory characteristics, and disease prognosis and outcomes in TD-NSAA patients. The clinical and laboratory data of 124 consecutive TD-NSAA patients in the Chinese Eastern Collaboration Group of Anemia from December 2013 and January 2017 were analyzed retrospectively. In 124 TD-NSAA patients, the median age was 32 years (range: 3-80) and the median disease course was 38 months (range: 3-363). Common complications were iron overload (53/101, 52.5%), liver and kidney dysfunction (42/124, 33.9%), diabetes mellitus/impaired glucose tolerance (24/124, 19.4%), and severe infection (29 cases, 23.4%). 58% of patients (57/124) developed severe aplastic anemia with a median progression time of 24 months (range: 3-216). Patients with absolute neutrophil count (ANC) <0.5×109/L, severe infection, or iron overload had a higher probability of progression to SAA (P=0.022, P=0.025, P=0.001). Patients receiving antithymocyte globulin (ATG) plus Cyclosporin A (CsA) had a higher overall response rate compared to those receiving CsA alone (56.7% vs 19.3%, P < 0.001). The addition of ATG was the favorable factor for efficacy (P=0.003). Fourteen patients developed secondary clonal hematologic disease: eleven patients with paroxysmal nocturnal hemoglobinuria, two patients with myelodysplastic syndromes, and one patient with acute myeloid leukemia, respectively. Ten patients (8.1%) died with a median follow-up of 12 months (range: 3- 36 months). Patients with TD-NSAA usually have a prolonged course of disease, and are prone to be complicated with important organ damage and disease progression to SAA. Intensive immunosuppressive therapy based on ATG might be an appropriate approach for TD-NSAA. Clinical trial registration: http://www.chictr.org.cn/edit.aspx?pid=125480&htm=4, identifier ChiCTR2100045895.

KMT2A is targeted by miR-361-3p and modulates leukemia cell's abilities to proliferate, migrate and invade.

OBJECTIVE: The lives and safety of humans are significantly threatened by acute myeloid leukemia (AML), which is proven to be the most prevalent acute leukemia. This work is therefore intended to investigate and analyze the expressions of miR-361-3p and Histone Lysine Methyltransferase 2A (KMT2A) in tissues and cell lines of AML and identify an advanced and novel target for the therapy of AML. METHODS: The qRT-PCR and western blot assays were conducted to find expressions of miR-361-3p/KMT2A in AML PB and cell lines. After then, tests using CCK-8 and EdU were run to see how KMT2A affected the growth of AML cells. Transwell migration and invasion assay was conducted to evaluate KMT2A's contribution to the migration and invasion of AML cells. ENCORI and miRWalk predicted the association between KMT2A and miR-361-3p, and the dual-luciferase reporter experiment verified it. Furthermore, rescue studies were used to ascertain how KMT2A affected the miR-361-3p-regulated AML cells' abilities to proliferate, migrate, and invade. RESULTS: miR-361-3p was poorly expressed while KMT2A was abundantly expressed. Additionally, KMT2A downregulation prevented AML cells from proliferating. PCNA and Ki-67 protein levels fell when KMT2A was silent. Furthermore, AML cells' motility, invasion, and metastasis were inhibited by low KMT2A expression. KMT2A was also identified as a direct target of miR-361-3p and negatively correlated with miR-361-3p. Finally, the over-expression of KMT2A partially reversed the inhibitory effects of up-regulation of miR-361-3p. CONCLUSION: A potential therapeutic candidate target for the treatment of AML may be miR-361-3p/KMT2A.

Comparison of haploidentical-allogeneic hematopoietic stem cell transplantation and intensive immunosuppressive therapy for patients with severe aplastic anemia with an absolute neutrophil count of zero: a retrospective study.

A retrospective analysis was conducted based on the clinical data from 60 patients older than 16 years from January 2016 to January 2021. All the patients were newly diagnosed with severe aplastic anemia (SAA) with an absolute neutrophil count (ANC) of zero. We compared the hematological response and survival of haploidentical-allogeneic hematopoietic stem cell transplantation (HID-HSCT) (n = 25) and intensive immunosuppressive therapy (IST) (n = 35) treatments. At six months, the overall response rate and complete response were significantly higher in the HID-HSCT group than those in the IST group (84.0% vs. 40.0%, P = 0.001; 80.0% vs. 17.1%, P = 0.001). With a median follow-up of 18.5 months (4.3~30.8 months), patients in the HID-HSCT group had longer overall survival and event-free survival (80.0% vs. 47.9%, P = 0.0419; 79.2% vs. 33.5%, P = 0.0048). These data suggested that HID-HSCT might be an effective alternative treatment option for adult patients with SAA with an ANC of zero, which requires further validation in an additional prospective study.

Prolonged use of eltrombopag in patients with severe aplastic anemia in the real world.

Eltrombopag (EPAG) can improve the efficacy of immunosuppressive therapy (IST) consisting of antithymocyte immunoglobulin (ATG) and cyclosporin in severe aplastic anemia (SAA) patients. This study explored whether patients with SAA could benefit from continuous usage of EPAG beyond 6 months.Seventy-four treatment-naive Chinese patients with SAA were administrated with rabbit ATG-based IST plus EPAG for 6 months. Patients not achieving complete remission (CR) at 6 months were treated with EPAG for another 6 months.At 1, 3, 6 and 12 months after IST, the cumulative response rates were 31%, 61%, 82% and 90%, and the cumulative CR rates were 0, 14%, 27% and 45%, respectively. The cumulative effect curve showed that 93% and 53% of all remission and CR occurred within 6 months, while 98% and 83% of all remission and CR occurred within 12 months. Thirty-seven percent of patients (11 of 30) with partial remission (PR) at 6 months continuously exposed to EPAG improved to CR within 3 (1-5) months of the extended median time. Six patients failing at 6 months continued to use EPAG. Three patients showed improved responses with an extended median time of 6 (1-6) months. The 2-year event-free survival (EFS) was better in those continuing with EPAG (89% vs. 49%, P = 0.006) for patients with PR or non-remission at 6 months.Continuous administration with EPAG could improve the hematologic response and EFS in patients without achieving CR at 6 months.This trial has been registered at the Chinese Clinical Trial Registry (ChiCTR2100045895).

Iron chelation of hetrombopag in aplastic anemia: a post hoc analysis of a phase II study.

Hetrombopag is the only CFDA-approved thrombopoietin (TPO) receptor agonist for severe aplastic anemia (SAA) in China. Its chemical structure has an iron chelation domain. To explore the iron chelation effect of hetrombopag, we performed a post hoc analysis of the phase II clinical trial (NCT03557099). Thirty-five immunosuppressive therapy (IST)-refractory SAA patients were enrolled in the study, and the longitudinal changes of serum ferritin (SF) were assessed. At 18 weeks post-hetrombopag initiation, 51.4% of patients showed decreased SF levels by a median of 49.0 (18.1-95.5) % from baseline (median ΔSF decrease value, 917.2 ng/ml, range from 104.0 to 7030.0 ng/ml). A decrease in SF was found in 75.0% of hematologic responders and 31.6% of non-responders. Among the 24 patients with iron overload, 12 had decreased SF levels by up to 51% of the baseline. Patients with normal SF levels also showed decreased SF levels, and iron deficiency occurred in two patients. In conclusion, hetrombopag showed a powerful and rapid iron chelation effect.

Efficacy and safety of ruxolitinib in patients with myelofibrosis and low platelet count (50 × 109/L to <100 × 109/L) at baseline: the final analysis of EXPAND.

Background: Thrombocytopenia is a common feature of myelofibrosis (MF), a myeloproliferative neoplasm driven by dysregulated JAK/STAT signaling; however, pivotal trials assessing the efficacy of ruxolitinib (a JAK1/2 inhibitor) excluded MF patients with low platelet counts (<100 × 109/L). Objectives: Determination of the maximum safe starting dose (MSSD) of ruxolitinib was the primary endpoint, with long-term safety and efficacy as secondary and exploratory endpoints, respectively. Design: EXPAND (NCT01317875) was a phase 1b, open-label, ruxolitinib dose-finding study in patients with MF and low platelet counts (50 to <100 × 109/L). Methods: Patients were stratified according to baseline platelet count into stratum 1 (S1, 75 to <100 × 109/L) or stratum 2 (S2, 50 to <75 × 109/L). Previous analyses established the MSSD at 10 mg twice daily (bid); long-term results are reported here. Results: Of 69 enrolled patients, 38 received ruxolitinib at the MSSD (S1, n = 20; S2, n = 18) and are the focus of this analysis. The incidence of adverse events was consistent with the known safety profile of ruxolitinib, with thrombocytopenia (S1, 50%; S2, 78%) and anemia (S1, 55%; S2, 44%) the most frequently reported adverse events and no new or unexpected safety signals. Substantial clinical benefits were observed for patients in both strata: 50% (10/20) and 67% (12/18) of patients in S1 and S2, respectively, achieved a spleen response (defined as ⩾50% reduction in spleen length from baseline) at any time during the study. Conclusion: The final safety and efficacy results from EXPAND support the use of a 10 mg bid starting dose of ruxolitinib in patients with MF and platelet counts 50 to <100 × 109/L. Registration: ClinicalTrials.gov NCT01317875.

A real-word experience of eltrombopag plus rabbit antithymocyte immunoglobulin-based IST in Chinese patients with severe aplastic anemia.

Eltrombopag (EPAG), a thrombopoietin receptor agonist, was approved for the treatment of severe aplastic anemia (SAA) combined with immunosuppressive therapy (IST). However, the effects of real-life use of low doses of EPAG combined with rabbit antithymocyte globulin (ATG)-based IST in Asian patients with SAA are yet unknown. A total of 121 previously untreated Chinese patients with SAA were enrolled in a multicenter registry of the Chinese Eastern Collaboration Group of Anemia (2014-2020): 67 patients received IST alone and 54 patients received additional EPAG. Patients receiving IST plus EPAG had a higher overall response rate (ORR) at 1 month (P = 0.002), 3 months (P = 0.028), 6 months (P = 0.006), and 12 months (P = 0.031) compared to those receiving IST alone. EPAG was the favorable factor for response efficacy at 6 months. The complete response rate in the EPAG plus IST group was 17% at 3 months, 27% at 6 months, and 32% at 12 months, compared to 7% (P = 0.069), 14% (P = 0.11), and 33% (P = 0.92) for those treated with IST alone. The 2-year overall survival rate in EPAG plus IST and IST alone groups was 98% and 88%, respectively (P = 0.078). The rate of adverse events, including clonal evolution, infection, and transaminitis, was similar in the two cohorts. The addition of EPAG to IST was well-tolerated and associated with high rates of hematologic responses among the previously untreated Chinese patients with SAA.

Predicting Response of Severe Aplastic Anemia to Rabbit-Antithymocyte Immunoglobulin Based Immunosuppressive Therapy Combined With Eltrombopag.

Addition of eltrombopag (E-PAG) to intensive immunosuppressive therapy (IST) contributes to restoring hematopoiesis in patients with severe aplastic anemia (SAA). Used at relatively low doses in the East Asian population, the efficacies of E-PAG and the predictors for efficacy are not clear. We conducted a retrospective, multicenter study to analyze the efficacy and the possible predicting factors at 6 months in 58 adult SAA patients with rabbit ATG-based IST and E-PAG. The response rate and complete response rate at 6 months were 76% and 21%, respectively. The baseline reticulocyte percentage [area under a curve (AUC)=0.798, 95% confidence interval (CI) 0.640-0.956, P=0.006], absolute reticulocyte count (ARC) (AUC =0.808, 95%CI 0.647-0.970, P=0.004), red cell distribution width - coefficient of variation (RDW-CV) (AUC=0.722, 95%CI 0.494-0.950, P=0.040), and absolute lymphocyte count (ALC) (AUC=0.706, 95%CI 0.522-0.890, P=0.057) were highly predictive of response at 6 months. The tipping values of reticulocyte percentage, ARC, RDW-CV, and ALC were 0.45%, 7.36×109/L, 11.75%, and 1.06×109/L, respectively. The sensitivity and specificity of reticulocyte percentages were 81.6% and 66.7%; ARC were 86.8% and 66.7%, RDW-CV were 94.7% and 55.6%; ALC were 55.3% and 88.9%. At a median follow-up of 15.5 months, the 2-year cumulative overall survival was 92%. The baseline reticulocyte percentage, ARC, RDW-CV, and ALC were potential factors in predicting a favorable effect of rabbit-ATG based IST plus E-PAG in SAA patients of East Asia (ChiCTR2100045895). Clinical Trial Registration: http://www.chictr.org.cn/edit.aspx?pid=125480&htm=4, identifier ChiCTR2100045895.

Frontline Therapy Options for Adults With Newly Diagnosed Severe Aplastic Anemia: Intensive immunosuppressive Therapy Plus Eltrombopag or Matched Sibling Donor Hematopoietic Stem Cell Transplantation?

Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disease. Allogeneic hematopoietic stem cell transplantation from a matched sibling donor (MSD-HSCT) and intensive immunosuppressive therapy (IST) are 2 major comparable treatments for SAA. As the addition of eltrombopag (EPAG) to standard IST therapy has greatly improved the survival prognosis of SAA, whether MSD-HSCT or IST/EPAG is the better choice has become a matter of debate. A study was performed involving 99 patients with newly diagnosed acquired SAA from 5 medical centers, including 48 MSD-HSCT cases and 51 IST/EPAG cases, which consisted of rabbit antithymocyte globulin or porcine-antilymphocyte globulin, cyclosporine plus eltrombopag. The results suggested that patients treated with MSD-HSCT or IST/EPAG had similar overall survival (OS) rates exceeding 95% (P = .97). However, the event-free survival rate (EFS) of IST/EPAG (71.0%) was significantly lower than that of MSD-HSCT (89.6%), P = .04. Subgroup analysis indicated that the OS of the MSD-HSCT group was superior to that of the IST/EPAG group (100% versus 85.7%, P = .04) among those with very severe aplastic anemia (VSAA). Both the complete response rate (CR) and overall response rate (OR) with MSD-HSCT were significantly higher than those with IST/EPAG (CR: 79.2% versus 15.7%, P < .001; OR: 97.9% versus 72.6%, P = .001). In conclusion, IST/EPAG or MSD-HSCT treatment achieves an equally high OS in SAA, but MSD-HSCT leads to a better OS in patients with VSAA and shows advantages in improving EFS and accelerating hematopoietic reconstruction in patients with SAA.

A multicenter phase II study on the efficacy and safety of hetrombopag in patients with severe aplastic anemia refractory to immunosuppressive therapy.

Background: In this single-arm phase II study (NCT03557099), we evaluated the efficacy and safety of hetrombopag, a small molecule thrombopoietin (TPO) receptor agonist, in patients with severe aplastic anemia (SAA) who were refractory to standard first-line immunosuppressive therapy (IST). Methods: SAA patients who were refractory to standard first-line IST were given hetrombopag orally at an initial dose of 7.5 mg once daily to a maximum of 15 mg once daily, for a total of 52 weeks. The primary endpoint was proportion of patients achieving hematologic responses in ⩾1 lineage at week 18. Results: A total of 55 eligible patients were enrolled and received hetrombopag treatment. This study met its primary endpoint, with 23 [41.8%, 95% confidence interval (CI) = 28.7-55.9] patients achieving hematologic response in ⩾1 lineage at week 18 after initiation of hetrombopag treatment. Twenty-four (43.6%, 95% CI = 30.3-57.7) and 27 (49.1%, 95% CI = 35.4-62.9) of the 55 patients responded in ⩾1 lineage at weeks 24 and 52, respectively. Median time to initial hematologic response was 7.9 weeks (range = 2.0-32.1). The responses were durable, with a 12-month relapse-free survival rate of 82.2% (95% CI = 62.2-92.2). Adverse events occurred in 54 (98.2%) patients, and 28 (50.9%) patients had treatment-related adverse events. Seventeen (30.9%) patients had adverse events of grade ⩾3. Serious adverse events occurred in 15 (27.3%) patients and three deaths (5.5%) were reported. Conclusion: Hetrombopag showed encouraging efficacy with durable hematologic responses in patients with SAA who were refractory to IST. Hetrombopag was well tolerant and safe for long-term use. ClinicalTrialsgov identifier: NCT03557099.

Clinical characteristics and outcomes of 100 adult patients with pure red cell aplasia.

Adult pure red cell aplasia (PRCA) is a rare syndrome characterized by a severe normocytic anemia, reticulocytopenia, and absence of erythroblasts from bone marrow. The standard treatment has not yet been established for PRCA, although cyclosporine (CsA), corticosteroids (CS) showed a response in PRCA. We retrospectively analyzed the clinical data of 60 primary and 40 secondary adult patients with acquired PRCA. The proportion of secondary PRCA is relatively high and commonly associated with large granular lymphocyte leukemia (LGLL) (28 cases, 70.0%). The remission-induced regimens included CS, CsA, or other agents, and the response rate was 66.7%, 71.4%, and 50%, respectively (P = 0.336). When treating with CsA, the response rate of LGLL-associated PRCA was lower than primary PRCA (42.1% vs 85.7%, P = 0.001). Logistic regression analysis showed that ORR was inversely related to LGLL-associated PRCA. LGLL-associated PRCA had poor therapeutic efficacy to CsA.