Acta Haematologica最新文献

{"title":"Disseminated Mucormycosis and T-Cell-Depleted Allogeneic Stem Cell Transplantation: An Unusual Case Study.","authors":"Oana Diana Dragoi, Mili Shah, Victoria Potter, Daniele Avenoso, Pramila Krishnamurthy, Alireza Abdolrasouli, Silke Schelenz, Julie Chandra, Varun Mehra","doi":"10.1159/000540640","DOIUrl":"10.1159/000540640","url":null,"abstract":"<p><strong>Introduction: </strong>Invasive fungal infections are a primary cause of morbidity and mortality in patients with haematological malignancies.</p><p><strong>Case presentation: </strong>We describe an unusual clinical and radiological presentation of invasive mucormycosis (IM) in a 69-year-old patient with relapsed acute myeloid leukaemia. The patient was diagnosed with disseminated IM with involvement of the central nervous system in an atypical location, lung, spleen, muscle, bone, and heart, after having completed induction and bridging chemotherapy to allogeneic haematopoietic stem cell transplant (HSCT). Her clinical presentation was atypical with mild neurological symptoms slowly progressing over 2 months and without appropriate signs of systemic inflammation. Mucorales was eventually confirmed from bronchoalveolar lavage and subdural collection.</p><p><strong>Conclusion: </strong>This report highlights the difficult challenges of managing disseminated IM in an immunocompromised patient, where close multidisciplinary specialist care enabled successful treatment, followed by T-cell-depleted allogeneic HSCT for a high-risk haematological malignancy.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"1-7"},"PeriodicalIF":1.7,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Latin-American Experience in POEMS Syndrome: A Study of the GELAMM (Grupo de Estudio Latinoamericano de Mieloma Múltiple).","authors":"Moisés Manuel Gallardo-Pérez, Paola Negrete-Rodríguez, Morie A Gertz, Camila Peña, Eloisa Riva, Virginia Gilli, Gloritza Rodríguez, César Samánez, Joaquín Ferreira, Sergio Portiño, Jacqueline Montaña, Pilar León, Yaima Gutiérrez, Caroline Del-Castanhel, Cristian Seehaus, Maria Eugenia Funes, Rodrigo Meneces-Bustillo, Patricio Duarte, Claudia Shanley, Giannini Elvira, Paola Ochoa, Hernán López-Vidal, Humberto Martinez-Cordero, Jule Vasquez, Alana von-Glasenapp, Javiera Donoso, Jose Luis Viñuela, Guillermo J Ruiz-Delgado, Guillermo J Ruiz-Argüelles","doi":"10.1159/000540890","DOIUrl":"10.1159/000540890","url":null,"abstract":"<p><strong>Introduction: </strong>POEMS syndrome is a rare paraneoplastic syndrome caused by an underlying plasma cell disorder. The acronym refers to the following features: polyradiculoneuropathy, organomegaly, endocrinopathy, monoclonal paraproteinemia, and skin changes.</p><p><strong>Methods: </strong>The study was conducted at 24 hematological centers across 8 Latin-American countries. The study included a total of 46 patients {median age was 52 years (interquartile range [IQR]: 42-61.5), 30 males and 16 females} fulfilling the POEMS syndrome criteria diagnosed over a period of 12 years (January 1, 2011, through July 31, 2023). Epidemiological and clinical data were collected in an ad hoc database sent to the members of GELAMM, as well as the Kolmogorov-Smirnov test and Kaplan-Meier estimates.</p><p><strong>Results: </strong>All patients had polyneuropathy and monoclonal gammopathy; 89% had bone marrow plasma cell infiltration, 33% had sclerotic bone lesions. Only 10 patients underwent vascular endothelial growth factor (VEGF) testing in plasma samples. The paraproteinemia was IgG λ in 32% and IgA λ in 30%. 59% patients presented with cutaneous changes, mainly hyperpigmentation, 54% had organomegaly, and 74% endocrinopathy. The median interval from symptom onset to diagnosis was 7.7 months (IQR: 4.0-12.6). 69% of patients received a single line of treatment. The median follow-up period was 25 months (IQR: 9.37-52.0) and the 2-year overall survival rate was 100%. All patients who underwent transplantation (43%) are alive, with a median follow-up of 45.62 months (IQR: 15.46-70).</p><p><strong>Conclusion: </strong>This study investigates POEMS syndrome in Latin America and presents an initial overview of the disease in the region. VEGF usage is recommended for accurate diagnosis, but only 7 hematology centers in the region used it. Survival rate in Latin America is comparable with those observed internationally.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"1-9"},"PeriodicalIF":1.7,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Factors for Chronic Thrombocytopenia in Systemic Lupus Erythematosus with Immune Thrombocytopenia.","authors":"Soo Min Ahn, Eun-Ji Choi, Ji Seon Oh, Yong-Gil Kim, Chang-Keun Lee, Bin Yoo, Seokchan Hong","doi":"10.1159/000540192","DOIUrl":"10.1159/000540192","url":null,"abstract":"<p><strong>Introduction: </strong>We aimed to identify the clinical characteristics and risk factors for chronic immune thrombocytopenia (ITP) in patients with systemic lupus erythematosus (SLE).</p><p><strong>Methods: </strong>We retrospectively reviewed patients diagnosed with SLE-associated ITP between January 2000 and December 2021. Patient characteristics were analyzed according to the progression of chronic thrombocytopenia. No response was defined as a platelet count &lt;30 × 109/L or less than double the baseline count after treatment. Factors associated with chronic ITP were evaluated by logistic regression analysis.</p><p><strong>Results: </strong>Among the 121 patients with SLE-associated ITP, 27 progressed to chronic ITP lasting more than 1 year after initial diagnosis. The median initial platelet count was significantly lower in patients with chronic thrombocytopenia than in those without the disease (16 vs. 51 × 109/L). Patients who did not achieve a response within 1 month of treatment exhibited a high probability of progressing to chronic ITP (55.6 vs. 22.3%, p &lt; 0.001). Multivariable analysis revealed that severe thrombocytopenia at baseline (&lt;20 × 109/L) (adjusted odds ratio [aOR] = 13.628, 95% confidence interval [CI] = 3.976-46.791) and no response within 1 month (aOR = 9.171, 95% CI = 2.776-30.298) were significantly associated with the risk of progression to chronic ITP in patients with SLE. Approximately one-quarter of the patients with SLE-associated ITP progressed to chronic ITP.</p><p><strong>Conclusion: </strong>Severe thrombocytopenia and failure to achieve a response within 1 month were risk factors for the development of chronic ITP in those patients.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"1-9"},"PeriodicalIF":1.7,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case of Recurrent Localized Pulmonary Nodular Light Chain Amyloidosis Treated with Daratumumab plus CyBorD.","authors":"Ted Raddell, Farah Ashraf, Xiaofeng Zhao, Osheen Abramian, Tulin Budak-Alpdogan","doi":"10.1159/000540272","DOIUrl":"10.1159/000540272","url":null,"abstract":"<p><strong>Introduction: </strong>Nodular pulmonary amyloidosis (NPA) is a localized form of light chain (AL) amyloidosis often found incidentally and typically has an indolent and benign disease course treated with resection or local excision. We present a patient with recurrent localized AL amyloidosis who required further treatment.</p><p><strong>Case presentation: </strong>A 63-year-old female with monoclonal gammopathy of undetermined significance (MGUS) was found to have pulmonary AL amyloid on wedge resection and later had recurrence. The patient did not have signs of clonal plasma cell proliferation or systemic AL amyloid. She was treated with daratumumab, cyclophosphamide, bortezomib, and dexamethasone. After initiation of treatment, the patient has had significant hematologic and radiographic response.</p><p><strong>Conclusion: </strong>The patient had NPA recurrence with organ dysfunction without systemic disease. Because the presentation of recurrent pulmonary AL amyloidosis is rare, there is no published evidence on treatment. However, the patient has had hematologic and radiographic improvement after initiating treatment with a systemic protocol.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"1-6"},"PeriodicalIF":1.7,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Follow-Up of Eltrombopag Treatment for Patients with Cyclosporin A Refractory/Relapsed Transfusion-Dependent Non-Severe Aplastic Anemia: A Report from a Single Center in China.","authors":"Qinglin Hu, Yuan Yang, Chen Yang, Miao Chen, Bing Han","doi":"10.1159/000539905","DOIUrl":"10.1159/000539905","url":null,"abstract":"<p><strong>Introduction: </strong>Aplastic anemia (AA) is characterized by bone marrow failure and cytopenia. Eltrombopag (ELT) is effective and safe for treating refractory/relapsed AA; however, reports on the long-term outcomes of transfusion-dependent non-severe AA (TD-NSAA) are limited.</p><p><strong>Methods: </strong>Patients with TD-NSAA refractory to immunosuppressive therapy (IST) or relapsed after IST, treated with ELT alone, and followed up for at least 12 months were retrospectively enrolled. The baseline characteristics of patients, efficacy and adverse effects of ELT, and relapse and clone evolution rates after ELT were documented.</p><p><strong>Results: </strong>Of the 55 patients with TD-NSAA included, 24 (43.6%) were men. Median age at diagnosis was 46 (19-80) years. Twenty-four patients had relapsed TD-NSAA, and 31 patients had refractory TD-NSAA. During the median follow-up period of 28 (12-48) months, the overall and complete response rates at 3, 6, and 12 months of ELT treatment were 38.2, 60.0, and 52.7 and 9.1, 14.6, and 9.1%, respectively. After a median follow-up of 28 (12-48) months, 21.2% (7/33) of patients experienced relapse, with a median duration from ELT treatment to relapse of 14 (6-45) months.</p><p><strong>Conclusion: </strong>ELT was effective in patients with relapsed/refractory TD-NSAA, with tolerable adverse effects.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"1-10"},"PeriodicalIF":1.7,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factor VIII Levels and ISTH Disseminated Intravascular Coagulation Scores Do Not Distinguish Disseminated Intravascular Coagulation from the Coagulopathy of Liver Disease.","authors":"Cecily Allen, Marina Heskel, Ayesha Butt, Christopher Tormey, Alexander B Pine, Alfred I Lee, Samir Gautam","doi":"10.1159/000540239","DOIUrl":"10.1159/000540239","url":null,"abstract":"<p><strong>Introduction: </strong>Distinguishing disseminated intravascular coagulation (DIC) from the coagulopathy of liver disease represents a common clinical challenge. Here, we evaluated the utility of two diagnostic tools frequently used to differentiate between these conditions: factor VIII (FVIII) levels and the International Society on Thrombosis and Hemostasis (ISTH) DIC score.</p><p><strong>Methods: </strong>To this end, we conducted a retrospective chart review of patients with DIC, liver disease, or both. Multiple logistic regression was performed, and receiver operating characteristic curves were generated to calculate the area under curve (AUC) for distinguishing DIC in the setting of liver disease.</p><p><strong>Results: </strong>Among 123 patients with DIC, liver disease, or liver disease plus DIC, FVIII levels did not differ significantly. ISTH scores were lower in patients with DIC than in liver disease with or without DIC. Addition of several laboratory parameters to the ISTH score, including mean platelet volume, FV, FVIII, international normalized ratio, and activated partial thromboplastin time, improved AUC for distinguishing DIC in liver disease from liver disease alone (AUC = 0.76; p &lt; 0.0001).</p><p><strong>Conclusion: </strong>We conclude that FVIII levels do not distinguish DIC from liver disease, and ISTH DIC scores are not predictive of DIC in patients with liver disease. Inclusion of additional lab variables within the ISTH DIC score may aid in identifying DIC in patients with liver disease.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"1-5"},"PeriodicalIF":1.7,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Survival of Chronic Myelomonocytic Leukemia-Dysplastic over Proliferative Subtype after Allogeneic Hematopoietic Cell Transplant: A Tertiary Center Experience and Literature Review.","authors":"Hunter D Niehus, Jean Sabile, Richard T Maziarz, Gabrielle Meyers, Rachel Cook, Arpita P Gandhi, Jennifer N Saultz, Shauna Rakshe, Andy Kaempf, Theodore Braun, Yazan Migdady","doi":"10.1159/000539880","DOIUrl":"10.1159/000539880","url":null,"abstract":"<p><strong>Introduction: </strong>CMML is a rare neoplasm with overlapping myelodysplastic and myeloproliferative features whose only potential cure is allogeneic hematopoietic cell transplantation (allo-HCT).</p><p><strong>Methods: </strong>This retrospective study examined 27 CMML patients with high-risk clinical features who underwent first allo-HCT at our institution between 2004 and 2022.</p><p><strong>Results: </strong>Nineteen patients were diagnosed with the proliferative subtype (CMML-MPN) and 8 with the dysplastic subtype (CMML-MDS). Median OS was 15 months post-HCT (95% CI: 5-71); OS at 1, 3, and 5 years was 52%, 35%, and 35%, respectively. Compared to those with CMML-MPN, patients with CMML-MDS had longer OS (median, 8.6 vs. 0.9 years; p = 0.025), RFS (4.4 vs. 0.5 years; p = 0.021), and GVHD-free, relapse-free survival (GRFS, 9.4 vs. 3.4 months; p = 0.033) as well as lower 1-year NRM (13 vs. 47%; p = 0.043), with the statistical significance of this CMML subtype effect maintained in multivariable models. High-risk cytogenetics were associated with shorter GRFS in the univariable (median, 3.1 vs. 6.2 months; p = 0.013) and multivariable (HR = 4.88; p = 0.006) settings.</p><p><strong>Conclusions: </strong>Patients who underwent transplant for CMML-MDS experienced substantially better outcomes than those transplanted for CMML-MPN. Future studies are needed for transplantation optimization in CMML, especially CMML-MPN.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"1-10"},"PeriodicalIF":1.7,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Digital Health Coaching on Self-Efficacy and Patient-Reported Outcomes in Individuals with Acute Myeloid and Chronic Lymphocytic Leukemia: A Pilot Randomized Controlled Trial.","authors":"Jennifer Marvin-Peek, Valerie Shelton, Kelly Brassil, Bryan Fellman, Austin Barr, Kelly Sharon Chien, Danielle Hammond, Mahesh Swaminathan, Nitin Jain, William Wierda, Alessandra Ferrajoli, Courtney DiNardo","doi":"10.1159/000539756","DOIUrl":"10.1159/000539756","url":null,"abstract":"<p><strong>Introduction: </strong>Promotion of self-efficacy can enhance engagement with health care and treatment adherence in patients with cancer. We report the outcomes of a pilot trial of a digital health coach intervention in patients with leukemia with the aim of improving self-efficacy.</p><p><strong>Methods: </strong>Adult patients with newly diagnosed acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) were randomized 1:1 to a digital health coach intervention or standard of care. The primary outcome of self-efficacy was measured by the Cancer Behavior Inventory (CBI) score.</p><p><strong>Results: </strong>A total of 147 patients (37 AML, 110 CLL) were enrolled from July 2020 to December 2022. In the AML cohort, there was a mean increase in CBI score of 7.03 in the digital health coaching arm compared to a mean decrease of -3.57 in the control arm at 30 days (p = 0.219). There were no significant associations between the intervention and other patient-reported outcomes for patients with CLL.</p><p><strong>Conclusion: </strong>There were numerical, but not statistically significant increases in self-efficacy metrics in AML patients who received digital health coaching. Although this trial was underpowered due to enrollment limitations during a pandemic, digital health coaching may provide benefit to patients with hematologic malignancy and warrants further investigation.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"1-10"},"PeriodicalIF":1.7,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic-Guided Hydroxyurea to Reduce Transfusions in Ugandan Children with Sickle Cell Anemia: Study Design of the Alternative Dosing And Prevention of Transfusions Trial.","authors":"Alexandra Power-Hays, Ruth Namazzi, Charles Kato, Kathryn E McElhinney, Andrea L Conroy, Heather Hume, Chandy John, Sara M O'Hara, Susan E Stuber, Adam Lane, Teresa S Latham, Robert O Opoka, Russell E Ware","doi":"10.1159/000539541","DOIUrl":"10.1159/000539541","url":null,"abstract":"<p><strong>Introduction: </strong>People with sickle cell anemia (SCA) may require frequent blood transfusions to treat acute and chronic complications. Hydroxyurea is a life-saving treatment for SCA that could also decrease the need for blood transfusions. Inadequate medication access and challenges in dose optimization limit the widespread use of hydroxyurea in Africa. If feasible, pharmacokinetic (PK) dosing might improve dose determination to minimize toxicities and maximize clinical benefits. The Alternative Dosing And Prevention of Transfusions (ADAPT, NCT05662098) trial will analyze the impact of hydroxyurea on transfusion rate and serve as a pilot study to evaluate the feasibility of PK-guided hydroxyurea dosing in Uganda.</p><p><strong>Methods: </strong>Herein we describe the rationale and design of ADAPT, a prospective cohort study of ∼100 children with SCA in Jinja, Uganda. The primary hypothesis is that hydroxyurea will decrease blood transfusion use by ≥ 50%, comparing the transfusion incidence rate ratio between a 3-month pretreatment and a 12-month treatment period. A key secondary hypothesis is that our PK-dosing approach will generate a suitable hydroxyurea dose for ≥80% of participants. Every ADAPT participant will undergo hydroxyurea PK testing, and if a dose is generated within 15-35 mg/kg/day, participants will start on their individualized dose. If not, they will start on a default dose of 20 mg/kg/day. Hydroxyurea dose optimization will occur with periodic dose adjustments.</p><p><strong>Conclusion: </strong>Overall, demonstrating the reduction in blood transfusion utilization with hydroxyurea treatment would provide leverage to increase hydroxyurea access, and PK-guided hydroxyurea dosing should optimize the safe and effective treatment of SCA across sub-Saharan Africa.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"1-12"},"PeriodicalIF":1.7,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of Extended Pirtobrutinib Exposure in Relapsed and/or Refractory B-Cell Malignancies.","authors":"Lindsey E Roeker, Catherine C Coombs, Nirav N Shah, Wojciech Jurczak, Jennifer A Woyach, Chan Y Cheah, Krish Patel, Kami Maddocks, Yucai Wang, Pier Luigi Zinzani, Talha Munir, Youngil Koh, Meghan C Thompson, Catherine E Muehlenbein, Chunxiao Wang, Richard Sizelove, Sarang Abhyankar, Safarulla Hasanabba, Donald E Tsai, Toby A Eyre, Michael Wang","doi":"10.1159/000539587","DOIUrl":"10.1159/000539587","url":null,"abstract":"<p><strong>Introduction: </strong>Pirtobrutinib, a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor, has demonstrated promising efficacy in B-cell malignancies and is associated with low rates of discontinuation and dose reduction. Pirtobrutinib is administered until disease progression or toxicity, necessitating an understanding of the safety profile in patients with extended treatment.</p><p><strong>Methods: </strong>Here we report the safety of pirtobrutinib in patients with relapsed/refractory B-cell malignancies with extended (≥12 months) drug exposure from the BRUIN trial. Assessments included median time-to-first-occurrence of adverse events (AEs), dose reductions, and discontinuations due to treatment-emergent AEs (TEAEs) and select AEs of interest (AESIs).</p><p><strong>Results: </strong>Of 773 patients enrolled, 326 (42%) received treatment for ≥12 months. In the extended exposure cohort, the median time-on-treatment was 19 months. The most common all-cause TEAEs were fatigue (32%) and diarrhea (31%). TEAEs leading to dose reduction occurred in 23 (7%) and discontinuations in 11 (3%) extended exposure patients. One patient had a fatal treatment-related AE (COVID-19 pneumonia). Infections (73.0%) were the most common AESI with a median time-to-first-occurrence of 7.4 months. Majority of TEAEs and AESIs occurred during the first year of therapy.</p><p><strong>Conclusions: </strong>Pirtobrutinib therapy continues to demonstrate an excellent safety profile amenable to long-term administration without evidence of new or worsening toxicity signals.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"1-17"},"PeriodicalIF":1.7,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}