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In patients with low-risk polycythemia vera, exposure to low-dose Ropeginterferon alfa-2b (Ropeg) 100 µg every 2 weeks for 2 years was more effective than the standard treatment of therapeutic phlebotomy in maintaining target hematocrit (HCT) (< 45%) with a reduction in the need for phlebotomy without disease progression. In the present paper, we analyzed drug survival, defined as a surrogate measure of the efficacy, safety, adherence, and tolerability of Ropeg in patients followed up to 5 years. During the first 2 years, Ropeg and phlebotomy-only (Phl-O) were discontinued in 33% and 70% of patients, respectively, for lack of response (12 in the Ropeg arm vs. 34 in the Phl-O arm) or adverse events (6 vs. 0) and withdrawal of consent in (3 vs. 10). Thirty-six Ropeg responders continued the drug for up to 3 years, and the probability of drug survival after a median of 3.15 years was 59%. Notably, the primary composite endpoint was maintained in 97%, 94%, and 94% of patients still on drug at 3, 4, and 5 years, respectively, and 60% of cases were phlebotomy-free. Twenty-three of 63 Phl-O patients (37%) failed the primary endpoint and were crossed over to Ropeg; among the risk factors for this failure, the need for more than three bloodletting procedures in the first 6 months emerged as the most important determinant. In conclusion, to improve the effectiveness of Ropeg, we suggest increasing the dose and using it earlier driven by high phlebotomy need in the first 6 months post-diagnosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: In myelodysplastic syndromes (MDS), severe thrombocytopenia is associated with poor prognosis. This multicenter trial presents the second-part long-term efficacy and safety results of eltrombopag in patients with low-risk MDS and severe thrombocytopenia., Methods: In this single-blind, randomized, placebo-controlled, phase-II trial of adult patients with International Prognostic Scoring System low- or intermediate-1-risk MDS, patients with a stable platelet (PLT) count (<30 × 10 3 /mm 3 ) received eltrombopag or placebo until disease progression. Primary end points were duration of PLT response (PLT-R; calculated from the time of PLT-R to date of loss of PLT-R, defined as bleeding/PLT count <30 × 10 3 /mm 3 or last date in observation) and long-term safety and tolerability. Secondary end points included incidence and severity of bleeding, PLT transfusions, quality of life, leukemia-free survival, progression-free survival, overall survival and pharmacokinetics., Results: From 2011 to 2021, of 325 patients screened, 169 patients were randomly assigned oral eltrombopag (N = 112) or placebo (N = 57) at a starting dose of 50 mg once daily to maximum of 300 mg. PLT-R, with 25-week follow-up (IQR, 14-68) occurred in 47/111 (42.3%) eltrombopag patients versus 6/54 (11.1%) in placebo (odds ratio, 5.9; 95% CI, 2.3 to 14.9; P < .001). In eltrombopag patients, 12/47 (25.5%) lost the PLT-R, with cumulative thrombocytopenia relapse-free survival at 60 months of 63.6% (95% CI, 46.0 to 81.2). Clinically significant bleeding (WHO bleeding score ≥ 2) occurred less frequently in the eltrombopag arm than in the placebo group (incidence rate ratio, 0.54; 95% CI, 0.38 to 0.75; P = .0002). Although no difference in the frequency of grade 1-2 adverse events (AEs) was observed, a higher proportion of eltrombopag patients experienced grade 3-4 AEs (χ 2 = 9.5, P = .002). AML evolution and/or disease progression occurred in 17% (for both) of eltrombopag and placebo patients with no difference in survival times., Conclusion: Eltrombopag was effective and relatively safe in low-risk MDS with severe thrombocytopenia. This trial is registered with ClinicalTrials.gov identifier: NCT02912208 and EU Clinical Trials Register: EudraCT No. 2010-022890-33.

BACKGROUND: Whether phlebotomy alone can adequately maintain target hematocrit in patients with low-risk polycythemia vera (PV) remains elusive. METHODS: In a phase 2 open-label randomized trial, we compared ropeginterferon alfa-2b (ropeg; 100 μg every 2 weeks) with phlebotomy only regarding maintenance of a median hematocrit level (≤45%) over 12 months in the absence of progressive disease (primary end point). In follow-up, crossover to the alternative treatment group was allowed if the primary end point was not met. RESULTS: In total, 127 patients were enrolled (ropeg: n=64; standard group: n=63). The primary end point was met in 81% and 51% in the ropeg and standard groups, respectively. Responders continued the assigned treatment until month 24 and maintained response in 83% and 59%, respectively (P=0.02). Ropeg responders less frequently experienced moderate/severe symptoms (33% vs. 67% in the standard group) and palpable splenomegaly (14% vs. 37%) and showed normalization of ferritin levels and blood counts. Nonresponders at 12 months crossed over to the standard (n=9) or ropeg (n=23) group; in patients switched to ropeg only, 7 of 23 met the response criteria in 12 months, and phlebotomy need was high (4.7 per patient per year). Discontinuation because of adverse events occurred in seven patients treated with ropeg. CONCLUSIONS: In this 24-month trial, ropeg was superior to phlebotomy alone in maintaining hematocrit on target. No dose-limiting side effects or toxicities were noted; 9.2% of patients on ropeg and no patients on standard treatment developed neutropenia. (Funded by AOP Health and others; ClinicalTrials.gov number, NCT03003325.)

Background: Venetoclax in combination with hypomethylating agents (HMA) is revolutionizing the therapy of acute myeloid leukemia (AML). However, evidence on large sets of patients is lacking, especially in relapsed or refractory leukemia., Methods: AVALON is a multicentric cohort study that was conducted in Italy on patients with AML who received venetoclax-based therapies from 2015 to 2020. The study was approved by the ethics committee of the participating institution and was conducted in accordance with the Declaration of Helsinki. The effectiveness and toxicity of venetoclax + HMA in 190 (43 newly diagnosed, 68 refractory, and 79 relapsed) patients with AML are reported here., Results: In the newly diagnosed AML, the overall response rate and survival confirmed the brilliant results demonstrated in VIALE-A. In the relapsed or refractory AML, the combination demonstrated a surprisingly complete remission rate (44.1% in refractory and 39.7% in relapsed evaluable patients) and conferred to treated patients a good expectation of survival. Toxicities were overall manageable, and most incidents occurred in the first 60 days of therapy. Infections were confirmed as the most common nonhematologic adverse event., Conclusions: Real-life data show that the combination of venetoclax and HMA offers an expectation of remission and long-term survival to elderly, newly diagnosed patients, and to relapsed or chemoresistant AML, increasing the chance of cure through a different mechanism of action. The venetoclax + HMA combination is expected to constitute the base for triplet combinations and integration of target therapies. Our data contribute to ameliorate the understanding of venetoclax + HMA effectiveness and toxicities in real life., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

The combination of elotuzumab, lenalidomide, and dexamethasone (EloRd) enhanced the clinical benefit over Rd with a manageable toxicity profile in the ELOQUENT-2 trial, leading to its approval in relapsed/refractory multiple myeloma (RRMM). The present study is a 3-year follow-up update of a previously published Italian real-life RRMM cohort of patients treated with EloRd. This revised analysis entered 319 RRMM patients accrued in 41 Italian centers. After a median follow-up of 36 months (range 6-55), 236 patients experienced disease progression or died. Median progression-free survival (PFS) and overall survival (OS) were 18.4 and 34 months, respectively. The updated multivariate analyses showed a significant reduction of PFS and OS benefit magnitude only in cases with International Staging System stage III. Major adverse events included grade 3/4 neutropenia (18.5%), anemia (15.4%), lymphocytopenia (12.5%), and thrombocytopenia (10.7%), while infection rates and pneumonia were 33.9% and 18.9%, respectively. No new safety signals with longer follow-up have been observed. Of 319 patients, 245 (76.7%) reached at least a partial remission. A significantly lower response rate was found in patients previously exposed to lenalidomide. In conclusion, our study confirms that EloRd is a safe and effective regimen for RRMM patients, maintaining benefits across multiple unfavorable subgroups., (© 2022 John Wiley & Sons Ltd.)

Minimal residual disease (MRD) analysis is a known predictive tool in mantle cell lymphoma (MCL). We describe MRD results from the Fondazione Italiana Linfomi phase 3 MCL0208 prospective clinical trial assessing lenalidomide (LEN) maintenance vs observation after autologous stem cell transplantation (ASCT) in the first prospective comprehensive analysis of different techniques, molecular markers, and tissues (peripheral blood [PB] and bone marrow [BM]), taken at well-defined time points. Among the 300 patients enrolled, a molecular marker was identified in 250 (83%), allowing us to analyze 234 patients and 4351 analytical findings from 10 time points. ASCT induced high rates of molecular remission (91% in PB and 83% in BM, by quantitative real-time polymerase chain reaction [RQ-PCR]). Nevertheless, the number of patients with persistent clinical and molecular remission decreased over time in both arms (up to 30% after 36 months). MRD predicted early progression and long-term outcome, particularly from 6 months after ASCT (6-month time to progression [TTP] hazard ratio [HR], 3.83; P < .001). In single-timepoint analysis, BM outperformed PB, and RQ-PCR was more reliable, while nested PCR appeared applicable to a larger number of patients (234 vs 176). To improve MRD performance, we developed a time-varying kinetic model based on regularly updated MRD results and the MIPI (Mantle Cell Lymphoma International Prognostic Index), showing an area under the ROC (Receiver Operating Characteristic) curve (AUROC) of up to 0.87 using BM. Most notably, PB reached an AUROC of up to 0.81; with kinetic analysis, it was comparable to BM in performance. MRD is a powerful predictor over the entire natural history of MCL and is suitable for models with a continuous adaptation of patient risk. The study can be found in EudraCT N. 2009-012807-25 (https://eudract.ema.europa.eu/)., (© 2022 by The American Society of Hematology.)

Background: The clinical management of patients with relapsed or refractory multiple myeloma is challenging and there is a paucity of tools to help clinicians make more informed decisions for the most suitable treatment options. We aimed to investigate the clinical utility of the International Myeloma Working Group (IMWG) frailty score in the setting of relapsed or refractory multiple myeloma, by examining its ability to capture different patient-reported health-related quality of life profiles., Methods: We did a cross-sectional analysis of a prospective observational study of patients with relapsed or refractory multiple myeloma in Italy and the UK (30 hospitals across northern, central, and southern Italy, and one hospital in London, UK). Inclusion criteria were age 18 years or older and patients who had received at least one previous line of therapy and no more than five lines. Participants were excluded if they had a psychiatric disorder or major cognitive dysfunction, or any grade 3 or higher adverse event within 2 weeks before study entry. On study initiation, physicians had to assess frailty according to the IMWG criteria, which included the Charlson Comorbidity Index, the Katz Activity of Daily Living, and the Lawton Instrumental Activities of Daily Living. Patients were asked to complete patient-reported outcome measures, including the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30) and its validated multiple myeloma module (QLQ-MY20). A multivariable linear regression model was used to assess the mean differences in health-related quality of life scores between frailty groups to account for key potential confounding factors., Findings: Overall, between Nov 13, 2017, and Nov 15, 2021, 415 patients with relapsed or refractory multiple myeloma, with a median age of 69·8 years (IQR 62·8-75·2) were enrolled. The median time since diagnosis was 4·4 years (IQR 2·5-7·1) and most patients (351 [85%]) had received at least two previous lines of therapy. According to the IMWG frailty score, 200 (48%) were classified as fit, 112 (27%) were classified as intermediate-fit, and 103 (25%) patients were classified as frail. Each frailty group was associated with a distinct health-related quality of life profile, with most notable differences between fit and frail patients. The largest clinically meaningful adjusted differences between fit and frail patients by the EORTC QLQ-C30 questionnaire were observed for physical functioning (Δ=-19·0 [95% CI -25·6 to -12·5; p<0·0001), fatigue (Δ=16·7 [9·7 to 23·7]; p<0·0001), insomnia (Δ=13·4 [4·1 to 22·6]; p=0·0047), and dyspnoea (Δ=12·5 [4·6 to 20·4]; p=0·0021). The most prevalent clinically important symptom in the overall population was pain; however, its prevalence varied between IMWG frailty groups at 70·9% in frail patients, 55·9% in intermediate-fit patients, and 50·5% in fit patients., Interpretation: Our findings show the clinical utility of the IMWG frailty score in the setting of relapsed or refractory multiple myeloma, in helping to distinguish between groups of patients with distinct health-related quality of life profiles. Further research is needed to examine the value of patient-reported outcome data in improving assessment of frailty in the setting of relapsed or refractory multiple myeloma., Funding: Fondazione GIMEMA Franco Mandelli Onlus and Amgen., Competing Interests: Declaration of interests AL has received honoraria from and served on the advisory boards for Janssen-Cilag, Bristol Myers Squibb, Amgen, Takeda, Oncopeptides, GlaxoSmithKline, Sanofi, and Karyopharm, outside of the submitted work. CF reports research support from Amgen and Celgene outside of the submitted work. EA is on the advisory boards and speaking bureaus for Amgen, BMS, Takeda, Sanofi, and Janssen outside of the submitted work. FE is a consultant and adviser for Amgen, AbbVie, Janssen, and Novartis and reports research support (to institution) from AbbVie and Novartis outside of the submitted work. FE also reports research support from Amgen ( to institution) during the conduct of the study. GG is on the advisory boards for AbbVie, AstraZeneca, Beigene, Incyte, Janssen, and Roche; and on the speaking bureaus for Abbvie and Janssen outside of the submitted work. GMR reports honoraria from AbbVie, AstraZeneca, Janssen, and Gilead and research support from Gilead outside of the submitted work. MC reports honoraria from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Takeda, AbbVie, Sanofi, Pfizer, GSK, and Adaptive Biotechnologies, and is on the speaking bureaus for Janssen and Celgene outside of the submitted work. MO reports honoraria from and is an adviser for Amgen, AbbVie, BMS, Celgene, GSK, Janssen, Roche, Sanofi, and Takeda outside of the submitted work. MTP reports honoraria from Janssen-Cilag, Celgene-BMS, Amgen, Sanofi, GSK, Takeda; is on the advisory boards for Janssen-Cilag, Celgene-BMS, Amgen, Sanofi, GSK, Takeda, Roche, and Karyopharm; and reports support for attending meetings or travel from Janssen-Cilag, Celgene-BMS, Amgen, Sanofi, and Takeda outside of the submitted work. MV reports honoraria from Amgen, Incyte, Novartis, Dephaforum Srl, AbbVie, and AstraZeneca and is on the advisory board for Amgen outside of the submitted work. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The present study aimed to develop two survival risk scores (RS) for overall survival (OS, SRS KRd/EloRd ) and progression-free survival (PFS, PRS KRd/EloRd ) in 919 relapsed/refractory multiple myeloma (RRMM) patients who received carfilzomib, lenalidomide, and dexamethasone (KRd)/elotuzumab, lenalidomide, and dexamethasone (EloRd). The median OS was 35.4 months, with no significant difference between the KRd arm versus the EloRd arm. In the multivariate analysis, advanced ISS (HR = 1.31; P = 0.025), interval diagnosis-therapy (HR = 1.46; P = 0.001), number of previous lines of therapies (HR = 1.96; P < 0.0001), older age (HR = 1.72; P < 0.0001), and prior lenalidomide exposure (HR = 1.30; P = 0.026) remained independently associated with death. The median PFS was 20.3 months, with no difference between the two strategies. The multivariate model identified a significant progression/death risk increase for ISS III (HR = 1.37; P = 0.002), >3 previous lines of therapies (HR = 1.67; P < 0.0001), older age (HR = 1.64; P < 0.0001), and prior lenalidomide exposure (HR = 1.35; P = 0.003). Three risk SRS KRd/EloRd categories were generated: low-risk (134 cases, 16.5%), intermediate-risk (467 cases, 57.3%), and high-risk categories (213 cases, 26.2%). The 1- and 2-year OS probability rates were 92.3% and 83.8% for the low-risk (HR = 1, reference category), 81.1% and 60.6% (HR = 2.73; P < 0.0001) for the intermediate-risk, and 65.5% and 42.5% (HR = 4.91; P < 0.0001) for the high-risk groups, respectively. Notably, unlike the low-risk group, which did not cross the median timeline, the OS median values were 36.6 and 18.6 months for the intermediate- and high-risk cases, respectively. Similarly, three PRS KRd/EloRd risk categories were engendered. Based on such grouping, 338 (41.5%) cases were allocated in the low-, 248 (30.5%) in the intermediate-, and 228 (28.0%) in the high-risk groups. The 1- and 2-year PFS probability rates were 71.4% and 54.5% for the low-risk (HR = 1, reference category), 68.9% and 43.7% (HR = 1.95; P < 0.0001) for the intermediate-risk, and 48.0% and 27.1% (HR = 3.73; P < 0.0001) for the high-risk groups, respectively. The PFS median values were 29.0, 21.0, and 11.7 months for the low-, intermediate-, and high-risk cases. This analysis showed 2.7- and 4.9-fold increased risk of death for the intermediate- and high-risk cases treated with KRd/EloRd as salvage therapy. The combined progression/death risks of the two categories were increased 1.3- and 2.2-fold compared to the low-risk group. In conclusion, SRS KRd/EloRd and PRS KRd/EloRd may represent accessible and globally applicable models in daily clinical practice and ultimately represent a prognostic tool for RRMM patients who received KRd or EloRd., Competing Interests: PT received honoraria from Bristol-Myers Squibb, Takeda, Janssen, Celgene, Amgen; LP received honoraria from Celgene, Takeda, Janssen, Amgen; EZ has received a speaker honorarium from Bristol-Myers Squibb, Takeda, Janssen, Celgene, Amgen; MC has received a speaker honorarium from Adaptive Biotechnology, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Takeda, AbbVie, GlaxoSmithKline and he is a member of committee of these Company; CC and FDR received honoraria from Amgen. CC, and FDR received honoraria from Celgene. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Morabito, Zamagni, Conticello, Pavone, Palmieri, Bringhen, Galli, Mangiacavalli, Derudas, Rossi, Ria, Catalano, Tacchetti, Mele, Vincelli, Martino, Vigna, Bruzzese, Mendicino, Botta, Mele, Pantani, Rocchi, Garibaldi, Cascavilla, Ballanti, Tripepi, Frigeri, Falcone, Cangialosi, Reddiconto, Farina, Barone, Rizzello, Iaccino, Mimmi, Curci, Gamberi, Musto, De Stefano, Musso, Petrucci, Offidani, Di Raimondo, Boccadoro, Cavo, Neri and Gentile.)

The lack of a randomized trial comparing carfilzomib (K) versus elotuzumab (Elo) associated with lenalidomide and dexamethasone (Rd) prompted us to assess the relative usefulness of one triplet over the other. Five independent retrospective cohorts of 883 relapsed/refractory multiple myeloma (RRMM) patients, including 300 EloRd and 583 KRd cases, outside clinical trials, entered this non-randomized comparison. KRd cohort accounted for a higher incidence of younger patients, cases with ≥3 lines of therapy, already exposed to lenalidomide, International Staging System (ISS) stage III, and abnormal lactic dehydrogenase (LDH) level compared with EloRd cohort. Moreover, cytogenetic risk categories, detected in roughly one-third of cases, were equally distributed between the two therapy arms. The probability of CR+VGPR response was significantly higher in KRd (n = 314, 53.9%) than in EloRd patients (n = 111, 37.0%). Likewise, the cumulative incidence function of CR+VGPR, taking into account the competitive risk of death, was significantly higher in KRd arm patients than those in the EloRd arm (p = .003). Moreover, KRd treatment significantly reduced the progression or death risk by 46% in an adjusted multivariate analysis (HR: 0.54, 95% CI 0.42-0.69, p < .0001). Finally, in an adjusted illness-progression/death model, the effect of KRd versus EloRd was of higher magnitude among those who achieved CR+VGPR (-39% hazard ratio reduction, p = .02) than among those who achieved < VGPR (-29% hazard ratio reduction, p = .007). With limitations characteristic to any retrospective analysis, this current clinical practice study's overall results demonstrated potential benefits of KRd therapy compared with EloRd. This observation may help the daily clinical practice., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Decitabine, a DNA hypomethylating agent, was approved for use in adults with acute myeloid leukemia (AML) not eligible for standard chemotherapy and is now widely accepted as standard treatment. Although a number of clinical trials demonstrated its benefits in elderly AML patients, older adults and patients with frequent comorbidities are typically under-represented in such settings. Thus, the aim of the present study is to evaluate, in a real-world setting, the effectiveness and toxicity of decitabine administered as a single agent in unselected previously untreated elderly AML patients not eligible for intensive chemotherapy. In nine hematological departments of the Apulian Hematological Network (REP), we enrolled 199 patients (median age: 75.4 years; range: 61-91) with de novo ( n = 94) or secondary/therapy-related ( n = 105) AML treated with decitabine 20 mg/m 2 for five days every 4 weeks. Hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using multivariate Cox regression. The average number of cycles administered per patient was 6.3 (SD: 6.0; median: 5 cycles). Complete response was achieved by 31 patients (15.6%) and partial response by 57 (28.6%), for a total of 88 responders overall (44.2%). After a median follow-up of 33.6 months, median OS was 8.7 months (95% CI: 7.4-10.3), and the 6-month, 1-year, and 3-year OS rates were 62.7%, 37.0%, and 7.1%, respectively. Mortality was increased in AML patients with ≥3 comorbidities (HR = 2.45; 95% CI: 1.18-5.08) vs. no comorbidities and in those with adverse karyotype (HR = 1.58; 95% CI: 1.05-2.38) vs. favourable or intermediate profile. Infection was the main registered adverse event (46.0%). In conclusion, this REP real-life study demonstrates, after a follow-up of almost 3 years, how decitabine administered to AML patients not suitable for intensive chemotherapy is effective and well tolerated, even in a population of truly elderly patients with frequent comorbidities.

Background: Nowadays minimal residual disease (MRD) and log-reduction of leukemic cells are poorly investigated in elderly patients with acute myeloid leukemia (AML) treated with hypometilating agents (HMAs). Studies focusing on MRD in elderly AML patients who received HMAs are scant and devoid of rigorous criteria for both enrollment and monitoring. Log-reduction has never been investigated in these patients. Thus, the purpose of our study was to compare the prognostic impact of MRD and log-reduction of leukemic cells at the optimal time of assessment in older AML patients., Methods: Elderly patients who completed at least six cycles of HMAs and showed suitable leukemia-associated immunophenotypes (LAIPs) for the MRD and log-reduction assessment by flow cytometry were enrolled in the study., Results: After comparing the times of assessment C4 (4-cycles) and C6 (6-cycles), C6 has been chosen as optimal. Patients who achieved MRD negativity or 2-log-reduction of leukemic cells at C6 had a significantly longer DFS. Particularly, results of 2-log-reduction were confirmed a multivariate analysis. Patients with MRD negativity or 2-log reduction of leukemic cells showed an improvement of their OS, although not significantly., Conclusions: Our data confirmed the predictive role of MRD and 2-log reduction also in older AML patients treated with HMAs., (© 2021 International Clinical Cytometry Society.)

Immune-mediated thrombotic thrombocytopenic purpura is a rare and challenging hematological disease caused by the antibody anti-ADAMTS13. Though the mortality rate has decreased considerably in recent years, fatalities still remain unacceptable. This study aimed at further adding to the existing knowledge of this medical challenge. We enrolled 89 consecutive patients observed in six Italian centers (from 8 August 2013 to 28 May 2021) with a diagnosis of immune-mediated thrombotic thrombocytopenic purpura. Clinical information and blood parameters were collected for all patients. We describe clinical manifestations and laboratory data, possible risk factors and the therapeutic management of first episodes or relapses. A total of 74 first episodes and 19 relapses (median 3 years (interquartile range (IQR): 2-7)) were recorded. Seventy percent of patients enrolled at the first episode showed neurological signs and/or symptoms. All the patients enrolled at the first episode were treated with plasma exchange (median = 12; IQR: 8-19.5) and methylprednisolone (1 mg/kg/day). Rituximab (375 mg/m 2 weekly for four weeks) and caplacizumab were given to 15 (20.2%) and 2 patients (2.6%), respectively. We observed an overall mortality of 5.4% in the follow-up (median 60 months; IQR: 36.0-103.5). All fatalities occurred after a diagnostic delay. Present data point to the importance of the early detection of factors mostly associated with poor outcomes. It is likely that use of caplacizumab could improve the prognosis in those patients.