European Journal of Haematology最新文献

{"title":"Maternal and Fetal Outcomes of Aplastic Anemia During Pregnancy and Delivery: Systematic Review and Meta-Analysis.","authors":"Aashima Arora, Arihant Jain, Deepesh Lad, Drishita Ganguly, Pankaj Khatri, Muhammad Aaqib Shamim, Bijaya Kumar Padhi, Amol N Patil, Pankaj Malhotra, Vanita Jain","doi":"10.1111/ejh.14317","DOIUrl":"https://doi.org/10.1111/ejh.14317","url":null,"abstract":"<p><strong>Background: </strong>Little scientific evidence exists on maternal and fetal outcomes in aplastic anemia (AA) during pregnancy.</p><p><strong>Aim: </strong>The review was conducted to assess the maternal and fetal outcomes due to AA during pregnancy.</p><p><strong>Data sources: </strong>Web of Science, EMBASE, PubMed, Scopus, Cochrane CENTRAL, and registries until May 5, 2024.</p><p><strong>Study eligibility criteria: </strong>Studies (prospective, retrospective cohort, cross-sectional, one arm, survey, follow-up studies) evaluating AA during pregnancy were searched as per PROSPERO registered protocol (CRD42024506668). Case reports, case series, expert opinion letters, and studies assessing less than or equal to 10 pregnant women were not considered. The primary outcome was the prevalence of preeclampsia in AA pregnancies. The secondary outcomes included spontaneous abortion, preterm premature rupture of membranes, premature rupture of membranes, fetal growth restriction, type of delivery, intrauterine fetal death, maternal and neonatal mortality, and pre and post-pregnancy remission status comparison.</p><p><strong>Methods: </strong>The quality of research was checked using the New Castle-Ottawa risk-of-bias tool. A meta-analysis model with a random effect distribution, coupled with meta-regression, sensitivity analysis, and publication bias assessment, was used in the statistical software R. Standard Equator network study reporting guidelines were followed.</p><p><strong>Results: </strong>Seven (one prospective and six retrospective cohort) studies included patients with confirmed AA diagnosis in 248 pregnancies. The pooled prevalence of preeclampsia was 13% (95% CI, 8%-20%). Heterogeneity was low in the present meta-analysis (I² = 26%). The secondary outcome evaluation showed a pooled prevalence of 5% (95% CI, 3%-11%) for spontaneous abortion, 4% (95% CI, 1%-11%) for preterm premature rupture of membranes, 10% (95% CI, 3%-28%) for premature rupture of membranes, 6% (95% CI, 3%-11%) for fetal growth restriction, 5% (95% CI, 2%-13%) for intrauterine fetal death, 12% (95% CI, 5%-26%) for post-partum hemorrhage, 74% (95% CI, 45%-91%) for intrapartum transfusion requirement, and 55% (95% CI, 27%-80%) for the cesarean delivery opting. The maternal mortality in pregnancies with AA was 4% (95% CI, 0.01-0.14), whereas neonatal mortality was 7% (95% CI, 0.03-0.18). The odds of AA complete remission were better in pre-pregnancy than post-pregnancy (OR = 0.36; 95% CI = 0.08-1.66), although the results remain insignificant. The leave-one-out sensitivity analysis did not change the pooled estimates for the primary outcome.</p><p><strong>Conclusion: </strong>A risk of developing preeclampsia was observed in every eighth pregnant woman with an AA diagnosis. AA remission status might worsen after undergoing pregnancy, considering the significant obstetric morbidity and mortality burden.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Evidence of Crizanlizumab Showing Reductions in Vaso-Occlusive Crises and Opioid Usage in Sickle Cell Disease.","authors":"Laurie DeBonnett, Vikas Joshi, Ana Cristina Silva-Pinto, Raffaella Colombatti, Annamaria Pasanisi, Francesco Arcioni, Rodolfo D Cançado, Séverine Sarp, Rajendra Sarkar, Wesam Soliman","doi":"10.1111/ejh.14323","DOIUrl":"https://doi.org/10.1111/ejh.14323","url":null,"abstract":"<p><strong>Objective: </strong>Access to crizanlizumab, a disease-modifying therapy for sickle cell disease (SCD), was provided through a managed access program (MAP, NCT03720626). The present analysis evaluated the impact of 12 months of crizanlizumab treatment on vaso-occlusive crises (VOCs), and on the use of opioids for VOC-related pain relief, in patients with SCD from the MAP.</p><p><strong>Methods: </strong>From June 2018 to January 2023, 112 patients with a history of recurrent VOCs completed 12 months of crizanlizumab (5 mg/kg) treatment and were monitored for adverse events (AEs).</p><p><strong>Results: </strong>Crizanlizumab led to reductions of 18.0% and 36.2% in the proportions of patients having ≥ 1 home- and ≥ 1 healthcare-managed VOCs. Median absolute changes (interquartile range) from baseline in the rates of home- and healthcare-managed VOCs were -3.0 (-6.0, -1.0) and -2.0 (-4.0, 0), respectively. Data stratified by genotype and prior hydroxyurea use showed similar reductions in VOC rates. A 35.5% reduction in the proportion of patients requiring opioids was noted. AEs were consistent with earlier reports, and no new safety concerns were identified.</p><p><strong>Conclusions: </strong>Crizanlizumab demonstrated potential benefits in attenuating VOC episodes, irrespective of SCD genotype and prior hydroxyurea use, and in lowering opioid usage. The safety of crizanlizumab was consistent with earlier reports.</p><p><strong>Trial registration: </strong>The MAP has been registered at ClinicalTrials.gov with the ID, NCT03720626.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ABO Blood Type and Short-Term Mortality in Patients With Infection-Associated Disseminated Intravascular Coagulation.","authors":"Simon Flæng, Asger Granfeldt, Kasper Adelborg, Henrik Toft Sørensen","doi":"10.1111/ejh.14329","DOIUrl":"https://doi.org/10.1111/ejh.14329","url":null,"abstract":"<p><strong>Background: </strong>Disseminated intravascular coagulation (DIC) is a devastating disease of the coagulation system. We examined the association between ABO blood type and short-term mortality in patients with infection-associated DIC.</p><p><strong>Methods: </strong>The study cohort was drawn from the Danish Disseminated Intravascular Coagulation (DANDIC) cohort. Our subcohort was restricted to patients with infection-associated DIC. All-cause 30-day and 90-day mortality were computed by Kaplan-Meier estimates and odds ratios between ABO blood types were examined using logistic regression analysis adjusted for age, sex, comorbidity, and location of infection. Blood type O was used as a reference.</p><p><strong>Results: </strong>The DANDIC cohort included 3023 patients with DIC. Among these, 1853 (61%) had infection-associated DIC. Data on ABO blood type were unavailable in 34 patients (1.8%), who were excluded. The median age was 68 years and 58.2% were males. The 30-day mortality ranged between 38.6% and 42.5% and the 30-day mortality odds ratios were 1.15 (95% confidence interval (CI), 0.92-1.42) for blood type A; 0.84 (95% CI, 0.49-1.43) for AB; and 0.95 (95% CI, 0.67-1.33) for B compared to blood type O.</p><p><strong>Conclusions: </strong>We found no clinically meaningful difference in short-term mortality between the various ABO blood types in patients with infection-associated DIC.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Analysis of Bispecific Antibodies and CAR T-Cell Therapy in Follicular Lymphoma","authors":"Fortunato Morabito,&nbsp;Enrica Antonia Martino,&nbsp;Maria Elena Nizzoli,&nbsp;Annalisa Talami,&nbsp;Stefano Pozzi,&nbsp;Massimo Martino,&nbsp;Antonino Neri,&nbsp;Massimo Gentile","doi":"10.1111/ejh.14335","DOIUrl":"10.1111/ejh.14335","url":null,"abstract":"<p>The treatment landscape for relapsed/refractory follicular lymphoma (RR-FL) is marked by a pivotal debate between chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAbs). While both CAR-T therapy and BsAbs target similar immunobiology and molecular markers, their efficacy comparisons are hindered by the lack of direct clinical trial comparisons. Key trials, such as the ZUMA-5 study, underscore axicabtagene ciloleucel (axi-cel)'s efficacy in treating RR-FL, achieving a 79% complete response rate with a median duration of response exceeding 3 years. Similarly, lisocabtagene maraleucel (liso-cel) in the TRANSCEND FL study reports a 94% complete response rate, emphasizing robust outcomes in heavily pretreated patients. Among BsAbs, mosunetuzumab showed promise in the GO29781 trial, with a 62% overall response rate in heavily pretreated RR-FL patients. Thus, CAR-T therapy offers potential curative benefits with a single infusion. However, its efficacy is tempered by significant adverse events such as cytokine release syndrome (CRS), neurotoxicity, and cytopenias, requiring specialized management and patient monitoring. In contrast, BsAbs provide a more tolerable treatment option counterbalancing by lower response rates and frequent dosing requirements. Personalized treatment strategies are crucial because of these distinct efficacy and safety profiles. When considering cost-effectiveness, both therapies need to be evaluated in the context of their clinical outcomes and quality of life improvements. Cost-effectiveness considerations are essential; while CAR-T therapies incur higher initial costs, their potential for long-term remission may mitigate expenses associated with repeated treatments or hospitalizations. Future research into resistance mechanisms and optimal therapeutic sequencing will further refine RR-FL management strategies.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 1","pages":"4-16"},"PeriodicalIF":2.3,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14335","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distance to CAR-T Treatment Center Does Not Impede Delivery.","authors":"Xiu Xia Sherry Tan, Melissa T Maltez, Ranjeeta Mallick, Linda Hamelin, Sheryl McDiarmid, Carolina Cieniak, Matthew Granger, Christopher Bredeson, Michael Kennah, Harold L Atkins, Natasha Kekre","doi":"10.1111/ejh.14331","DOIUrl":"https://doi.org/10.1111/ejh.14331","url":null,"abstract":"<p><strong>Background: </strong>Chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated remarkable efficacy in relapsed or refractory large B cell lymphoma, but real-world evidence is needed to confirm safety and efficacy when facing the unique challenges of a wide geographical catchment area.</p><p><strong>Methods: </strong>We reviewed patients treated with commercially available CAR-T at a medium-sized single center in Canada (The Ottawa Hospital) between December 2020 and July 2022 (Canadian implementation started in 2020).</p><p><strong>Results: </strong>Fifty-one patients (59% male, median age 62) traveled a median distance of 655 km (range 3-3659) for treatment. Median time from apheresis to CAR-T infusion was 36 days (range 26-81). With a median follow-up of 383 days (95% CI: 333-480), median progression-free survival (PFS) and overall survival (OS) were 257 days (95% CI: 92-NE) and 422 days (95% CI: 106-NE), respectively. The median PFS for out-of-province patients was 115 days (95% CI: 91-NE) versus 280 days for in-province patients (95% CI: 142-NE), p = 0.12. Multivariate analysis demonstrated that distance from treatment center (p = 0.05) and refractory disease status (p = 0.003) were independently associated with shorter PFS. The time from the last disease progression to CAR-T referral was longer for out-of-province patients, but there was no difference in the time of referral to CAR-T consult, apheresis, or CAR-T infusion between in-province and out-of-province patients.</p><p><strong>Conclusion: </strong>Our results confirm that despite the complexity of CAR-T therapy administration, Ottawa can effectively provide commercial CAR-T therapy in a timely fashion for patients from across the country.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Favorable Prognosis in Patients With Multiple Myeloma and Lenalidomide-Induced Skin Rash: A Multicenter Retrospective Study.","authors":"Ayumi Nakamura, Yuta Kimura, Yuka Tanaka, Daisuke Tsuchimoto, Atsuhiko Naruse, Tetsufumi Kanematsu, Kento Takeuchi, Nobukazu Tomita, Kenji Miyazawa, Tomohiro Fukuoka, Akiya Mori, Shinya Tamaki, Aiko Fujioka, Satoshi Yokoyama, Yoshiaki Ikeda, Hirokazu Nagai","doi":"10.1111/ejh.14333","DOIUrl":"https://doi.org/10.1111/ejh.14333","url":null,"abstract":"<p><p>Although lenalidomide is an essential treatment for multiple myeloma (MM), skin rashes are a common adverse event. This retrospective study aimed to examine the association between skin rash development during lenalidomide treatment and the prognosis of relapsed/refractory MM. All patients who received lenalidomide at 10 hospitals between July 2009 and December 2015 were included in the study. The relationship of skin rash development with disease progression and survival was evaluated. Multivariate analysis was performed to identify factors affecting disease progression or survival, including skin rash. Of the 245 patients analyzed, 70 developed skin rashes. The median progression-free survival (PFS) of patients with skin rashes was 22.4 months, whereas the median PFS for patients who did not develop skin rashes was 10.5 months (p = 0.003). The median overall survival for patients with and without skin rash was 42.6 and 24.6 months, respectively (p = 0.013). Multivariate regression analysis showed that skin rash was an independent prognostic factor for PFS (p = 0.009). In this study, patients with skin rashes during lenalidomide treatment had significantly better PFS than those without such symptoms, indicating that lenalidomide-associated skin rashes may be a predictor of clinical outcomes in patients with MM.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asciminib in Advanced-Line Treatment of Chronic Myeloid Leukemia.","authors":"Adi Shacham-Abulafia, Yulia Volcheck, Martin Ellis, Shirley Shapira, Sigal Tavor, Anna Gourevitch, Natalia Kreiniz, Anfisa Stanevski, Pia Raanani, Maya Koren-Michowitz","doi":"10.1111/ejh.14330","DOIUrl":"https://doi.org/10.1111/ejh.14330","url":null,"abstract":"<p><strong>Objectives: </strong>Asciminib, a novel allosteric BCR::ABL1 inhibitor, targets the ABL1 myristoyl pocket to potentially reduce toxicity and enhance efficacy. It is approved for Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia (CML-CP) in patients with resistance or intolerance to two or more tyrosine kinase inhibitors (TKIs) or those with the T315I mutation.</p><p><strong>Methods: </strong>This retrospective analysis evaluated patients with CML treated with asciminib under a managed-access program across eight Israeli centers from July 2019 to August 2022. We assessed treatment responses, toxicities, event-free survival (EFS), and overall survival (OS) using Kaplan-Meier methods.</p><p><strong>Results: </strong>The study included 30 patients who had received a median of three prior TKIs, with 73% starting asciminib due to intolerance. After a median follow-up of 7.1 months, 85% of those without prior complete cytogenetic response (CCyR) achieved CCyR, and 60% previously not in major molecular response (MMR) attained MMR. Resistance was rare (10%), with no cardiovascular events reported despite high baseline comorbidity (73%). Median EFS was 47 months; median OS was not reached.</p><p><strong>Conclusion: </strong>Asciminib demonstrates significant efficacy and tolerability in heavily pretreated patients with CML-CP, with no new cardiovascular events observed. Further long-term studies are necessary to explore its full cardiovascular impact.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Superior Prophylactic Effectiveness of a Recombinant FVIIIFc Over Standard Half-Life FVIII in Hemophilia A: A-SURE Study.","authors":"Johannes Oldenburg, Charles Hay, Flora Peyvandi, Annarita Tagliaferri, Pål Andrè Holme, María Teresa Álvarez-Román, Christine Biron-Andréani, Håkan Malmström, Linda Bystrická, Stefan Lethagen","doi":"10.1111/ejh.14309","DOIUrl":"10.1111/ejh.14309","url":null,"abstract":"<p><strong>Objectives: </strong>The 24-month, prospective, non-interventional, European multicenter A-SURE study evaluated the real-world effectiveness of prophylaxis using an extended half-life recombinant factor VIII (FVIII) Fc fusion protein, efmoroctocog alfa (hereinafter rFVIIIFc), compared with prophylaxis using standard half-life (SHL) FVIII products in patients with hemophilia A.</p><p><strong>Methods: </strong>Primary endpoints were annualized bleeding rate (ABR), annualized injection frequency, and annualized factor consumption. A comparative study design unique for an observational hemophilia study was implemented to reduce potential confounding in effectiveness estimates, wherein each patient prescribed rFVIIIFc was matched with one receiving SHL FVIII. Propensity scores were used for adjustment in statistical analyses.</p><p><strong>Results: </strong>Outcomes for all primary endpoints were significantly better in the rFVIIIFc group (n = 184) compared with the SHL FVIII group (n = 170): mean ABR 1.5 versus 2.3 (difference of -0.8; p = 0.0147); mean annualized injection frequency 114.4 versus 169.2 (difference of -54.8; p < 0.0001); and mean annualized factor consumption 243 024.2 versus 288 718.6 International Units (difference of 45 694.5; p = 0.0003). rFVIIIFc was well tolerated, with no inhibitor development.</p><p><strong>Conclusions: </strong>rFVIIIFc has superior prophylactic effectiveness versus SHL FVIII, providing higher bleed protection with fewer injections and lower factor consumption.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fetal Hemoglobin Decrease During Voxelotor Treatment.","authors":"Gonzalo De Luna, Anoosha Habibi, Stéphane Moutereau, Suella Martino, Jamila Alhamrouni, Celia Morel, Yanis Pelinski, Yosr Zaouali, Frédéric Galactéros, Pablo Bartolucci","doi":"10.1111/ejh.14332","DOIUrl":"https://doi.org/10.1111/ejh.14332","url":null,"abstract":"<p><p>Voxelotor modifies hemoglobin-oxygen affinity improving anemia and reducing hemolysis in sickle cell patients. However, the impact of Voxelotor on fetal hemoglobin (HbF) levels is unknown. We describe here variations of percentage of HbF measured by high performance liquid chromatography and mean corpuscular fetal Hb in a cohort of sickle cell patients treated with Voxelotor at Henri Mondor Sickle Cell Referral Center. Our data show a decrease in HbF levels in sickle cell patients after 6 months of treatment with Voxelotor, which is likely to be associated with an increase in the lifespan of red blood cells that are no longer prematurely removed from the circulation, particularly those with low HbF. This work raises the question of the risk of a rebound effect when stopping Voxelotor, which has a short half-life, during the time it takes to increase HbF.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pacritinib Response Is Associated With Overall Survival in Myelofibrosis: PERSIST-2 Landmark Analysis of Survival.","authors":"Helen Ajufo, Jan Philipp Bewersdorf, Claire Harrison, Francesca Palandri, John Mascarenhas, Jeanne Palmer, Aaron Gerds, Jean-Jacques Kiladjian, Sarah Buckley, Andriy Derkach, Karisse Roman-Torres, Raajit K Rampal","doi":"10.1111/ejh.14321","DOIUrl":"https://doi.org/10.1111/ejh.14321","url":null,"abstract":"<p><p>Spleen volume reduction (SVR) is a key endpoint in inhibitors of Janus kinase (JAK) inhibitor studies. Retrospective analyses have demonstrated an association between SVR and improved overall survival (OS) among patients treated with ruxolitinib with a platelet count > 100 × 10⁹/L. Whether this association occurs in patients with thrombocytopenia is unclear. Pacritinib, a JAK2/IRAK1/ACVR1 inhibitor, demonstrated improved SVR versus best available therapy (BAT [best available therapy]; including ruxolitinib) in patients with myelofibrosis and platelet counts ≤ 100 × 10⁹/L in the PERSIST-2 study. Patients on study at the start of the 12-week SVR window on pacritinib 200 mg twice daily or BAT were included. OS was evaluated among SVR responders versus non-responders using different SVR thresholds (≥ 35%, ≥ 20%, ≥ 10%, and > 0%). Among patients on pacritinib (n = 89), SVR ≥ 10% demonstrated the greatest separation in OS curves between responders and non-responders (HR, 0.00; 95% CI, 0.00-0.14; p < 0.01), though SVR ≥ 0% and SVR ≥ 20% were also associated with improved OS. No SVR threshold conferred OS benefit on BAT (n = 84), including ruxolitinib (n = 39). In patients with myelofibrosis and platelets ≤ 100 × 10⁹/L, achieving SVR on pacritinib, but not BAT (including ruxolitinib), was associated with significant OS benefit, suggesting that pacritinib may offer a unique survival advantage in patients with myelofibrosis and thrombocytopenia who achieve any SVR. Trial Registration: ClinicalTrials.gov number: NCT02055781.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}