ChemotherapyPub Date : 2023-01-01DOI: 10.1159/000527010
Joanna Drozd-Sokolowska, Krzysztof Mądry, Joanna Barankiewicz, Katarzyna Kobylińska, Przemysław Biecek, Jagoda Rytel, Ewa Karakulska-Prystupiuk, Kamila Skwierawska, Aleksander Salomon-Perzyński, Tomasz Stokłosa, Grzegorz Władysław Basak
{"title":"SARS-CoV-2 Infection in Patients Treated with Azacitidine and Venetoclax for Acute Leukemia: A Report of a Case Series Treated in a Single Institution.","authors":"Joanna Drozd-Sokolowska, Krzysztof Mądry, Joanna Barankiewicz, Katarzyna Kobylińska, Przemysław Biecek, Jagoda Rytel, Ewa Karakulska-Prystupiuk, Kamila Skwierawska, Aleksander Salomon-Perzyński, Tomasz Stokłosa, Grzegorz Władysław Basak","doi":"10.1159/000527010","DOIUrl":"https://doi.org/10.1159/000527010","url":null,"abstract":"<p><strong>Introduction: </strong>Venetoclax combined with azacitidine (AZA-VEN) constitutes an option for the treatment of acute myeloid leukemia. There are, however, no data on the COVID-19 incidence and outcome in patients treated with AZA-VEN.</p><p><strong>Methods: </strong>Patients with acute leukemia treated with AZA-VEN at a single institution were included in this prospective observational study.</p><p><strong>Results: </strong>Thirteen patients were enrolled, 46% with treatment-naïve, and 56% with relapsed/refractory disease. Fifty-four percent of patients were males; the median age was 69 years. Six patients (46%) developed COVID-19 during the observation time. The median time to COVID-19 was 24 days from the initiation of AZA-VEN. The 2-month cumulative incidence of COVID-19 was 46.2%. Two patients (33%) succumbed to COVID-19. The 100-day COVID-19-free survival from AZA-VEN initiation was 61%. The median follow-up time was 4.3 months.</p><p><strong>Discussion/conclusion: </strong>COVID-19 constitutes a frequent complication of AZA-VEN treatment in the era of the COVID-19 pandemic, leading to death in a significant proportion of patients.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":"68 1","pages":"16-22"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10598534","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}
ChemotherapyPub Date : 2023-01-01Epub Date: 2023-06-13DOI: 10.1159/000527059
Marianna Gentilini, Beatrice Casadei, Alice Morigi, Ginevra Lolli, Marco Ferrari, Matteo Carella, Lisa Argnani, Pier Luigi Zinzani
{"title":"Endobronchial Presentation of Hodgkin Lymphoma Responding to Pembrolizumab: A Case Report.","authors":"Marianna Gentilini, Beatrice Casadei, Alice Morigi, Ginevra Lolli, Marco Ferrari, Matteo Carella, Lisa Argnani, Pier Luigi Zinzani","doi":"10.1159/000527059","DOIUrl":"10.1159/000527059","url":null,"abstract":"<p><p>An endobronchial localization of Hodgkin lymphoma is rare, and few experiences since the 1900s have been reported in the literature. Here we report the first case of a relapsed/refractory Hodgkin lymphoma with a critical vegetative mass at the level of the trachea successfully treated with pembrolizumab.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"219-221"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9627346","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}
ChemotherapyPub Date : 2023-01-01DOI: 10.1159/000527536
MingZhong Ma, JianWei He, Bo Gao, JianXun Cao, DaMing Li, YongChun Li, Gang Huang, Xing Zhou
{"title":"Targeted Therapy of Non-Small Cell Lung Cancer and Liver Cancer: Functional Nanocarriers for the Delivery of Cisplatin and Tissue Factor Pathway Inhibitor-2.","authors":"MingZhong Ma, JianWei He, Bo Gao, JianXun Cao, DaMing Li, YongChun Li, Gang Huang, Xing Zhou","doi":"10.1159/000527536","DOIUrl":"https://doi.org/10.1159/000527536","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of the study was to construct folic acid-modified PEGylated paramagnetic nanoparticles (MNPs) co-carrying tissue factor pathway inhibitor-2 (TFPI-2) and cisplatin (CDDP), and to study the molecular-targeting and inhibitory effects of the nanocomposite on non-small cell lung cancer (NSCLC) and liver cancer.</p><p><strong>Methods: </strong>Nanocomposites were prepared using amino-modified iron oxide nanoparticles as carriers, co-loading CDDP and PEGylated FA/TFPI-2. Transmission electron microscopy, UV absorption spectrum, and dynamic light scattering were employed to characterize the morphology, structure, particle size, and zeta potential of the nanocomposite. The phenylenediamine method was used to detect the loading of CDDP, and the CCK-8 assay was used to detect the toxic effect of the nanocomposite on HUVECs, A549, and NCI-H460 cells. In tumor-bearing mice models, the antitumor effects of the nanocomposites were assessed using TUNEL staining (at the molecular level), reverse transcriptase quantitative polymerase chain reaction (at the gene level), hematoxylin and eosin staining (at the cellular level), and the appearance of the mice models.</p><p><strong>Results: </strong>The synthesized FA-MNP/CDDP/TFPI-2 nanocomposite was uniformly dispersed and spherical in shape (approximate diameter: 10 nm). The zeta potential of particles was -9.44 mV, and the average particle size was 25 nm. The loading amount of CDDP was 70.24 μg/mL (23.33%). The nanocomposite was nontoxic to HUVECs, while it showed a favorable inhibitory effect on A549 and NCI-H460 cells. In vivo experiments in mice demonstrated satisfactory imaging properties and therapeutic effects of nanocomposite against liver cancer.</p><p><strong>Discussion: </strong>FA-MNP/CDDP/TFPI-2 may provide insights for the development of new chemotherapeutic drugs.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":"68 2","pages":"73-86"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9936126","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}
ChemotherapyPub Date : 2023-01-01DOI: 10.1159/000523904
Lei Han, Guangxin Li, Huihui Li, Lei Zhao
{"title":"Risk of Immune-Related Pneumonitis with PD-1/PD-L1 Inhibitors in Different Cancer Types and Treatment Regimens: A Systematic Review and Meta-Analysis of 22 Randomized Controlled Trials.","authors":"Lei Han, Guangxin Li, Huihui Li, Lei Zhao","doi":"10.1159/000523904","DOIUrl":"https://doi.org/10.1159/000523904","url":null,"abstract":"<p><strong>Background: </strong>Pneumonitis, the specific toxicity associated with PD-1/PD-L1 inhibitors, is severe and potentially life-threatening, and its incidence and severity are poorly understood among different tumor types or treatment methods. This meta-analysis was performed to compare the incidence and severity of pneumonitis among different tumor types and treatment regimens.</p><p><strong>Methods: </strong>MEDLINE and Embase were retrieved until September 2021. Meta-analysis of the risk of pneumonitis was calculated using a fixed-effect model. Pooled analysis of the incidence of pneumonitis in different tumor types was performed using a metaprop function.</p><p><strong>Results: </strong>Twenty two randomized controlled trials (RCTs) (n = 10,700) were included for pool analysis, and eighteen RCTs (n = 8,852) were eligible for meta-analysis. For all-grade pneumonitis, the risk of the combination therapy (PD-1/PD-L1 plus CTLA-4 inhibitor) was 3.62 times significantly higher than that of monotherapy, and 4.06 and 1.78 times significantly higher than that of chemotherapy and placebo than monotherapy. The incidence of pneumonitis was not significantly different between PD-1/PD-L1 inhibitor versus ipilimumab or between low doses versus high doses. For high-grade (grade ≥3) pneumonitis, the risk in PD-1/PD-L1 inhibitors alone was 3.62 times significantly higher than chemotherapy. No significant difference was found in the incidence of pneumonitis between combination versus monotherapy, monotherapy versus placebo, combination versus ipilimumab alone, monotherapy versus ipilimumab alone, or low doses versus high doses.</p><p><strong>Conclusions: </strong>Compared with chemotherapy, PD-1/PD-L1 inhibitor monotherapy may cause more treatment-related pneumonitis. Increasing the dose of PD-1/PD-L1 inhibitor does not significantly increase the incidence of pneumonitis. Compared with the monotherapy, combination therapy does not increase the incidence of pneumonitis significantly.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":"68 1","pages":"1-15"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10652279","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}
ChemotherapyPub Date : 2023-01-01Epub Date: 2023-03-07DOI: 10.1159/000529972
Michael S Ewer, Steven M Ewer
{"title":"Arrhythmia in Bruton Tyrosine Kinase Inhibitor-Treated Patients: Unanswered Questions.","authors":"Michael S Ewer, Steven M Ewer","doi":"10.1159/000529972","DOIUrl":"10.1159/000529972","url":null,"abstract":"<p><p>(No abstract allowed for commentary).</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":"68 3","pages":"168-169"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10223994","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}
ChemotherapyPub Date : 2023-01-01Epub Date: 2022-10-21DOI: 10.1159/000526827
Ahmad Waleed Khatib, Samuel Maxwell Selub, Anton Uryvaey, Jalal Baranseh, Ayelet Shai
{"title":"Initiating Treatment with Low Fluorouracil Dose and Titrating According to Blood Levels in Patients Treated with a 46-Hour Continuous Infusion.","authors":"Ahmad Waleed Khatib, Samuel Maxwell Selub, Anton Uryvaey, Jalal Baranseh, Ayelet Shai","doi":"10.1159/000526827","DOIUrl":"10.1159/000526827","url":null,"abstract":"<p><strong>Introduction: </strong>Fluorouracil (5-FU) pharmacokinetics are variable, leading to a risk of toxicity in some patients and underdosing in others. Therapeutic drug monitoring of 5-FU was shown to reduce toxicity and increase efficacy. This study assessed the clinical utility of starting treatment with 70-80% of BSA calculated dose and titrating according to 5-FU blood levels and toxicity.</p><p><strong>Methods: </strong>A retrospective analysis of a prospectively collected database of 126 patients treated with regimens containing 5-FU bolus and continuous infusion for 46 h for whom the 5-FU blood level was collected at least once. Response,and date of progression, and death were collected for patients with colon and pancreatic cancer.</p><p><strong>Results: </strong>In multivariate analysis, 5-FU blood levels were correlated with 5-FU dose and with age, albeit a small effect size (coefficient = 0.007). Of patients with colon cancer treated with an initial lower 5-FU dose, 18% had a therapeutic 5-FU blood level. The median survival was similar in patients with metastatic colon cancer treated with lower doses and those treated with a full dose. Of patients with pancreatic cancer treated with lower doses, 40% had therapeutic blood levels. The median survival was 13 months in patients with metastatic pancreatic cancer treated with lower 5-FU doses.</p><p><strong>Conclusion: </strong>Starting treatment with low 5-FU dose was associated with patient survival comparable to other published data, and a sizeable percentage of patients had therapeutic blood levels. This approach can be considered, especially in elderly and frail patients.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":"68 2","pages":"95-101"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9584295","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":"Evaluation of a Novel Combination Therapy, Based on Trifluridine/Tipiracil and Fruquintinib, against Colorectal Cancer.","authors":"Mamoru Nukatsuka, Akio Fujioka, Hideki Nagase, Gotaro Tanaka, Hiroaki Hayashi","doi":"10.1159/000528867","DOIUrl":"https://doi.org/10.1159/000528867","url":null,"abstract":"<p><strong>Introduction: </strong>Trifluridine/tipiracil hydrochloride (FTD/TPI, Lonsurf®) is an oral antineoplastic agent that has been approved as late-stage chemotherapy for colorectal cancer. Its major mechanism of action is the dysfunction of tumoral DNA including DNA strand breaks and decreased replication. Fruquintinib (ELUNATE®) is a novel kinase inhibitor that selectively inhibits the vascular endothelial growth factor receptor-1, -2, and -3. In this study, we evaluated the antitumor activity of combination therapy with FTD/TPI and fruquintinib in vivo.</p><p><strong>Methods: </strong>The enhancement of the antitumor effects with FTD/TPI and fruquintinib combination, compared to the single drugs given alone was evaluated using two human colorectal cancer xenografts in nude mouse models. FTD/TPI (200 mg/kg) was orally administered for 5 consecutive days followed by 2 days of rest in a 7-day period. Fruquintinib (10 mg/kg) was orally administered consecutively for 2 and 3 weeks in SW48 and HCT 116 tumor-bearing models, respectively. After treatment with these agents, the microvessel density was evaluated by CD31 immunohistochemical analyses.</p><p><strong>Results: </strong>In both models, FTD/TPI and fruquintinib significantly inhibited tumor growth, and the activity of the combined treatment was significantly superior to that of either monotherapy. Body weight loss of greater than 20% was not observed in any group. A histochemical analysis showed nuclei enlargement, abnormal mitosis, and karyorrhexis in the FTD/TPI treatment group. The microvessel density in the HCT 116 tumors treated with FTD/TPI and fruquintinib was significantly lower than that in the control group.</p><p><strong>Conclusion: </strong>The combination of FTD/TPI and fruquintinib could be a promising treatment option for colorectal cancer.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":"68 2","pages":"102-110"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10233702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9936649","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}
ChemotherapyPub Date : 2023-01-01DOI: 10.1159/000525819
Fulvia Fanelli, Stefan Hohaus, Maria Cantonetti, Giuseppe Cimino, Elsa Pennese, Roberta Battistini, Eugenio Galli, Raffaella Cerretti, Anna Proia, Federica Fatone, Ida Provenzano, Elisabetta Abruzzese, Erica Finolezzi, Alessandro Pulsoni, Luigi Rigacci
{"title":"Impact of Pretransplant Salvage Therapies on Outcome of Hodgkin Lymphoma Patients Performing Allogeneic Transplant.","authors":"Fulvia Fanelli, Stefan Hohaus, Maria Cantonetti, Giuseppe Cimino, Elsa Pennese, Roberta Battistini, Eugenio Galli, Raffaella Cerretti, Anna Proia, Federica Fatone, Ida Provenzano, Elisabetta Abruzzese, Erica Finolezzi, Alessandro Pulsoni, Luigi Rigacci","doi":"10.1159/000525819","DOIUrl":"https://doi.org/10.1159/000525819","url":null,"abstract":"<p><strong>Background: </strong>Allogeneic transplant is an effective salvage therapy in patients with Hodgkin lymphoma (HL) relapsed or refractory (R/R) to previous treatments. In recent years, immunotherapies (conjugated antibody and checkpoint inhibitors [CPI]) showed interesting results and were used as bridge therapies to allotransplant.</p><p><strong>Aim: </strong>The aim of this retrospective study in Lazio region was to evaluate the impact of these new therapies on outcome after allogeneic hematopoietic stem cell transplantation (allo-SCT) in comparison with standard chemotherapies used in the past.</p><p><strong>Methods: </strong>We selected all consecutive patients with diagnosis of HL transplanted in four hematology transplant units, and we collected data obtained from patients' records concerning all the treatments before allo-SCT.</p><p><strong>Results: </strong>A total of 56 patients were enrolled in this study. All patients underwent allo-SCT for R/R HL. Seventeen patients (30%) received chemotherapy prior to allo-SCT (group B); they were treated between 2008 and 2015; and 39 patients (70%) received brentuximab vedotin (BV), CPI, or both before allo-SCT as a bridge to transplant (group A); they were treated between 2012 and 2020. Twenty-five patients were treated with BV alone, 2 with CPI alone, and 12 first with BV and then with CPI. No patient received concomitant BV and CPI. At 5 years from allo-SCT, overall survival (OS) was 59% and progression-free survival (PFS) was 65%. No statistical differences in OS or PFS were observed between patients in groups A and B. Relapse was significantly associated with a lower survival. The only factor associated with a reduced risk of relapse was development of any grade acute graft versus host disease (GVHD) (p > 0.02).</p><p><strong>Conclusions: </strong>This regional real-world experience shows the changes that have taken place in the last 10 years in R/R HL using new drugs to render a patient eligible for allo-SCT. This strategy appears to guarantee an impressive disease control with an increased risk of complications, for example, aGVHD, that appear to nullify this advantage at least in part.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":"68 3","pages":"131-137"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10223960","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":"Acute Hepatitis E Infection during Chemotherapy for Lung Cancer: A Case Report.","authors":"Hiroki Okumura, Atsushi Miyamoto, Fumitaka Suzuki, Hisashi Takaya","doi":"10.1159/000530802","DOIUrl":"https://doi.org/10.1159/000530802","url":null,"abstract":"<p><p>Acute hepatitis E, one of the causes of acute liver injury, has been increasingly diagnosed in developed countries in recent years. Misdiagnosis of acute hepatitis E virus (HEV) infection as drug-induced liver injury (DILI) may lead to discontinuation of effective chemotherapy. Thus, viral hepatitis, including hepatitis E, must be ruled out in the diagnosis of DILI. A 78-year-old woman with lung adenocarcinoma and multiple bone metastases received maintenance therapy with pemetrexed + pembrolizumab for a year. Increased aspartate aminotransferase and alanine aminotransferase levels, indicating acute liver injury, were observed. Initially, DILI was suspected, and she was given medications to lower the levels of hepatic enzymes. She was later admitted to the hospital with the chief complaint of general malaise and anorexia. Serum aspartate aminotransferase and alanine aminotransferase levels were markedly elevated (381 and 854 U/L, respectively). Acute HEV infection was diagnosed based on the detection of serum HEV immunoglobulin A antibodies. The patient received liver support therapy, and the serum hepatic enzymes recovered to normal levels. Chemotherapy was resumed without any subsequent relapse of hepatic enzyme elevation. When DILI is suspected during chemotherapy, exclusion of viral hepatitis is mandatory, which can be achieved by measuring markers of hepatitis viruses, including HEV, and examining the patient's detailed medical history.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":"68 3","pages":"155-159"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10226591","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}
ChemotherapyPub Date : 2023-01-01Epub Date: 2022-11-10DOI: 10.1159/000528019
Giuseppe Boriani, Pierantonio Menna, Riccardo Morgagni, Giorgio Minotti, Marco Vitolo
{"title":"Ibrutinib and Bruton's Tyrosine Kinase Inhibitors in Chronic Lymphocytic Leukemia: Focus on Atrial Fibrillation and Ventricular Tachyarrhythmias/Sudden Cardiac Death.","authors":"Giuseppe Boriani, Pierantonio Menna, Riccardo Morgagni, Giorgio Minotti, Marco Vitolo","doi":"10.1159/000528019","DOIUrl":"10.1159/000528019","url":null,"abstract":"<p><strong>Background: </strong>The natural history of chronic lymphocytic leukemia (CLL) was dramatically improved by the introduction of ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor. In this review, we aimed to summarize and critically evaluate the association between first- and second-generation BTK inhibitors and the risk of atrial fibrillation (AF) and ventricular arrhythmias (VA).</p><p><strong>Summary: </strong>Since the first clinical experience, the development of AF was observed as the result of off-target effects that likely combined with patient's predisposing risk factors and concomitant cardiac morbidities. More recently, both ibrutinib dose reduction and arrhythmia management allowed long-term treatment, with positive effects on progression-free survival and reduced all-cause mortality as well. Second-generation BTK inhibitors, acalabrutinib, and zanubrutinib have been tested and validated in CLL. A lower occurrence of AF as compared with ibrutinib has been found, although AF has always been a secondary endpoint of all studies that probed these agents.</p><p><strong>Key messages: </strong>For this reason, caution should be exercised before concluding that second-generation BTK inhibitors are safer than ibrutinib. Recent data on the effectiveness of ibrutinib over a follow-up of 8 years show a remarkable benefit on all-cause mortality, which is of great value also for interpreting the clinical impact of the few cases of VA and sudden cardiac death (SCD) reported for ibrutinib, independently of QT lengthening. Since a risk of VA and SCD has been recently reported also during treatment with second-generation BTK inhibitors, it appears that this risk, usually reaching its maximum size effect at long-term follow-up, likely denotes a class effect of BTK inhibitors.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":"68 2","pages":"61-72"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9584309","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}