Hematological Oncology最新文献

{"title":"Identifying and addressing unmet clinical needs in primary cutaneous B-cell lymphoma: A consensus-based paper from an ad-hoc international panel","authors":"Pietro Quaglino,&nbsp;Nicola Pimpinelli,&nbsp;Pier Luigi Zinzani,&nbsp;Marco Paulli,&nbsp;Stefano Pileri,&nbsp;Emilio Berti,&nbsp;Lorenzo Cerroni,&nbsp;Joan Guitart,&nbsp;Youn H. Kim,&nbsp;Serena Rupoli,&nbsp;Marco Santucci,&nbsp;Gabriele Simontacchi,&nbsp;Maarten Vermeer,&nbsp;Richard Hoppe,&nbsp;Barbara Pro,&nbsp;Steven H. Swerdlow,&nbsp;Giovanni Barosi","doi":"10.1002/hon.3215","DOIUrl":"10.1002/hon.3215","url":null,"abstract":"<p>Primary cutaneous B-cell lymphomas (PCBCLs) are lymphoproliferative disorders that appear on the skin without evidence of extracutaneous manifestations at the time of diagnosis. There is a lack of evidence-based guidelines for their clinical management due to the availability of very few large scale studies and controlled clinical trials. Here we present and discuss a series of major unmet clinical needs (UCNs) in the management of PCBCLs by a panel of 16 experts involved in research and clinical practice of PCBCL. The Panel produced recommendations on the appropriateness of the clinical decisions concerning the identified clinical needs and proposed research for improving the knowledge needed to solve them. Recommendations and proposals were achieved by multiple-step formalized procedures to reach a consensus after a comprehensive analysis of the scientific literature. Recommendations and proposals lay in the domain of classification uncertainties of PCBCL, optimization of diagnosis, optimization of prognosis, optimization of staging and critical issues on therapeutic strategies with particular focus on new treatments. These recommendations are intended for use not only by experts but above all by dermatologists and hematologists with limited experience in the field of PCBCLs as well as general practitioners.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124514","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":"Single-unit unrelated cord blood transplantation versus HLA-matched sibling transplantation in adults with advanced myelodysplastic syndrome: A registry-based study from the adult MDS working group of the Japanese society for transplantation and cellular therapy","authors":"Takaaki Konuma,&nbsp;Hidehiro Itonaga,&nbsp;Yoshimitsu Shimomura,&nbsp;Machiko Fujioka,&nbsp;Kazunari Aoki,&nbsp;Naoyuki Uchida,&nbsp;Makoto Onizuka,&nbsp;Atsushi Jinguji,&nbsp;Masatsugu Tanaka,&nbsp;Yasunori Ueda,&nbsp;Yuta Katayama,&nbsp;Masashi Sawa,&nbsp;Haruyuki Tanaka,&nbsp;Hirohisa Nakamae,&nbsp;Toshiro Kawakita,&nbsp;Yumiko Maruyama,&nbsp;Satoshi Takahashi,&nbsp;Fumihiko Ishimaru,&nbsp;Junya Kanda,&nbsp;Tatsuo Ichinohe,&nbsp;Yoshiko Atsuta","doi":"10.1002/hon.3217","DOIUrl":"10.1002/hon.3217","url":null,"abstract":"<p>Allogeneic hematopoietic stem cell transplantation (HCT) remains the only potential curative therapeutic modality for advanced myelodysplastic syndrome (MDS). Within HCT, the advancement of cord blood transplantation (CBT) procedures has resulted in a drastic expansion of CBT as a donor source for MDS. However, data comparing matched sibling donors (MSDs) HCT with CBT for advanced MDS, which was defined as refractory anemia with an excess of blasts (RAEB)-1 and RAEB-2 according to the World Health Organization classification at the time of HCT, have not been explored. We retrospectively compared survival and other posttransplant outcomes in 999 adult patients with advanced MDS after receiving allogeneic HCT in Japan between 2011 and 2020, using either MSD (<i>n</i> = 331) or single-unit unrelated cord blood (UCB) (<i>n</i> = 668). In the multivariate analysis, there were no significant differences in overall survival (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.90–1.34; <i>P</i> = 0.347), disease-free survival (HR, 1.01; 95% CI, 0.84–1.23; <i>P</i> = 0.845), relapse (HR, 0.88; 95% CI, 0.68–1.15; <i>P</i> = 0.370), or non-relapse mortality (HR, 1.15; 95% CI, 0.87–1.50; <i>P</i> = 0.310) between MSD recipients and UCB recipients. UCB was significantly associated with lower neutrophil (HR, 0.28; 95% CI, 0.24–0.33; <i>P</i> &lt; 0.001) and lower platelet (HR, 0.29; 95% CI, 0.23–0.36; <i>P</i> &lt; 0.001) recovery compared to MSD. UCB was significantly associated with a lower incidence of chronic graft-versus-host disease (GVHD) (HR, 0.57; 95% CI, 0.44–0.75; <i>P</i> &lt; 0.001) and extensive chronic GVHD (HR, 0.46; 95% CI, 0.32–0.67; <i>P</i> &lt; 0.001) compared to MSD. Similar results were observed after adjusting for differences between MSD and UCB recipients by propensity score matching analysis. Our study demonstrated that single CBT and MSD HCT had similar survival outcomes for adult patients with advanced MDS despite the lower hematopoietic recovery in CBT recipients and higher chronic GVHD in MSD recipients.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3217","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10018718","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":"Evaluation of the novel therapeutic anti-CCR7 antibody CAP-100 as an add-on therapy in chronic lymphocytic leukemia patients receiving venetoclax","authors":"Tamara Mateu-Albero,&nbsp;Ana Marcos-Jimenez,&nbsp;Pablo Delgado-Wicke,&nbsp;Fernando Terrón,&nbsp;Javier Loscertales,&nbsp;José María Serra López-Matencio,&nbsp;Cecilia Muñoz-Calleja,&nbsp;Carlos Cuesta-Mateos","doi":"10.1002/hon.3213","DOIUrl":"10.1002/hon.3213","url":null,"abstract":"<p>The Bruton's tyrosine kinase inhibitor ibrutinib and the B-cell lymphoma 2 anti-apoptotic protein inhibitor venetoclax provide high response rates in chronic lymphocytic leukemia (CLL). However, there is a growing number of patients that relapse after treatment or show refractory disease, thus new targets and agents are still needed. We have previously reported the chemokine receptor CCR7 as a relevant deregulated target in CLL and have developed CAP-100, a novel therapeutic anti-CCR7 antibody that is under evaluation for relapse/refractory CLL (NCT04704323). While CCR7 expression has been shown to be down-modulated in CLL patients treated with ibrutinib, whether venetoclax acts in a similar manner remains unaddressed. Here, we aimed to document the impact of venetoclax on CCR7 expression in CLL cells, as well as on the pre-clinical activity of CAP-100. To this end, we addressed CCR7 expression by flow cytometry and the antibody efficacy by means of in vitro chemotactic and antibody-dependent cell-mediated cytotoxicity (ADCC) assays. Our data indicate that venetoclax treatment did not significantly modify CCR7 expression pattern nor CAP-100 mechanisms of action. Together, these findings support CAP-100 as an adjuvant therapy to venetoclax that may introduce additional modes of action in CLL therapy.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9949141","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":"TNFRSF13B gene mutation in familial acute myeloid leukemia: A new piece in the complex scenario of hereditary predisposition?","authors":"Cosimo Cumbo,&nbsp;Paola Orsini,&nbsp;Francesco Tarantini,&nbsp;Luisa Anelli,&nbsp;Antonella Zagaria,&nbsp;Vincenzo Tragni,&nbsp;Nicoletta Coccaro,&nbsp;Giuseppina Tota,&nbsp;Elisa Parciante,&nbsp;Maria Rosa Conserva,&nbsp;Immacolata Redavid,&nbsp;Crescenzio Francesco Minervini,&nbsp;Angela Minervini,&nbsp;Immacolata Attolico,&nbsp;Mattia Gentile,&nbsp;Ciro Leonardo Pierri,&nbsp;Giorgina Specchia,&nbsp;Pellegrino Musto,&nbsp;Francesco Albano","doi":"10.1002/hon.3212","DOIUrl":"10.1002/hon.3212","url":null,"abstract":"<p><i>TNFRSF13B</i> mutations are widely associated with common variable immunodeficiency. <i>TNFRSF13B</i> was recently counted among relevant genes associated with childhood-onset of hematological malignancies; nonetheless, its role in acute myeloid leukemia (AML) remains unexplored. We report the study of a family with two cases of AML, sharing a germline <i>TNFRSF13B</i> mutation favoring the formation of a more stable complex with its ligand TNFSF13: a positive regulator of AML-initiating cells. Our data turn the spotlight onto the <i>TNFRSF13B</i> role in AML onset, inserting a new fragment into the complex scenario of a hereditary predisposition to myeloid neoplasms.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3212","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9927050","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":"Magnesium enhances the graft-versus-tumor effect of donor lymphocytic infusion on hematologic malignancies","authors":"Yan Wei,&nbsp;Jiayuan Guo,&nbsp;Ning Lu,&nbsp;Yi Liu,&nbsp;Lijun Wang,&nbsp;Lili Wang,&nbsp;Jian Bo,&nbsp;Honghua Li,&nbsp;Liping Dou,&nbsp;Daihong Liu,&nbsp;Chunji Gao","doi":"10.1002/hon.3207","DOIUrl":"10.1002/hon.3207","url":null,"abstract":"<p>Donor lymphocyte infusion (DLI) cures relapsed hematologic malignancies after allogeneic hematopoietic stem cell transplantation through the graft-versus-tumor (GVT) effect. Although the important role of magnesium in enhancing immunity has been mentioned in studies, limited clinical data have explored how magnesium affects the efficacy of DLI. Besides, although laboratory data demonstrate that magnesium can enhance CD8⁺ T cells effector function, whether magnesium regulates the tumor killing effect of peripheral blood mononuclear cells (PBMCs) remains to be explored. Here, for the retrospective study, we collected clinical data of relapsed patients receiving DLI and explored the relationship between different serum magnesium levels and patient outcomes. For in vitro studies, we investigated the effect of magnesium on the cytotoxicity of DLI cells which were PBMCs and preliminarily explored the mechanism. Eighty-one patients were enrolled in this study. It was found that the high post-DLI magnesium level was significantly associated with a higher incidence of complete remission (CR) or partial remission (CR/PR) and a higher possibility of survival. The magnesium level after DLI was an independent risk factor of overall survival. In vitro studies proved that increased magnesium enhanced the cytotoxic function of PBMCs on hematologic malignancies. Besides, magnesium modulated LFA-1 headpiece opening. When blocking the integrin-ligand interaction between LFA-1 and ICAM-1, the regulation effect of magnesium on PBMCs was weakened. Therefore, it was possible that magnesium regulated PBMCs effector function by stimulating LFA-1. These results show that serum magnesium levels affect immunological responses mediated by donor lymphocytes in hematologic malignancies.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10235136","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":"Safety and efficacy of parsaclisib in combination with obinutuzumab and bendamustine in patients with relapsed or refractory follicular lymphoma (CITADEL-102): A phase 1 study","authors":"Mehdi Hamadani,&nbsp;Morton Coleman,&nbsp;Ralph Boccia,&nbsp;Juraj Duras,&nbsp;Martin Hutchings,&nbsp;Pier Luigi Zinzani,&nbsp;Raul Cordoba,&nbsp;Mariana Bastos Oreiro,&nbsp;Vanessa Williams,&nbsp;Huiqing Liu,&nbsp;Michael Stouffs,&nbsp;Peter Langmuir,&nbsp;Juan-Manuel Sancho","doi":"10.1002/hon.3209","DOIUrl":"10.1002/hon.3209","url":null,"abstract":"<p>Parsaclisib is a potent and highly selective PI3Kδ inhibitor that has shown clinical benefit with monotherapy in a phase 2 study in relapsed or refractory (R/R) follicular lymphoma (FL). CITADEL-102 (NCT03039114), a phase 1, multicenter study, assessed the efficacy of parsaclisib in combination with obinutuzumab and bendamustine in patients with R/R FL. Patients were ≥18 years of age with histologically confirmed and documented CD20-positive FL, and R/R to previous rituximab-containing treatment regimens. Part one (safety run-in) determined the maximum tolerated dose of parsaclisib in combination with standard dosage regimens of obinutuzumab and bendamustine. Part two (dose expansion) was an open-label, single-group design evaluating safety, tolerability (primary endpoint), and efficacy (secondary endpoint) of parsaclisib combination therapy. Twenty-six patients were enrolled in CITADEL-102 and all patients received parsaclisib 20 mg once daily for 8 weeks, followed by 20 mg once weekly thereafter, in combination with obinutuzumab and bendamustine. One patient in safety run-in experienced a dose-limiting toxicity of grade 4 QT interval prolongation that was considered related to parsaclisib. Eight patients (30.8%) discontinued treatment due to treatment-emergent adverse events (TEAEs) of colitis (2 [7.7%]), alanine aminotransferase and aspartate aminotransferase increase (both in one patient [3.8%]), neutropenia, thrombocytopenia, QT prolongation, tonsil cancer, and maculopapular rash (each 1 [3.8%]). The most common reported TEAEs were pyrexia (53.8%), neutropenia (50.0%), and diarrhea (46.2%). Twenty-three patients (88.5%) experienced grade 3 or 4 TEAEs; the most common were neutropenia (34.6%), febrile neutropenia (23.1%), and thrombocytopenia (19.2%). Seventeen patients (65.4%) had a complete response and 3 patients (11.5%) had a partial response, for an objective response rate of 76.9%. Overall, results from CITADEL-102 suggest that the combination of parsaclisib with obinutuzumab and bendamustine did not result in unexpected safety events, with little evidence of synergistic toxicity, and demonstrated preliminary efficacy in patients with R/R FL who progressed following prior rituximab-containing regimens.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3209","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10235137","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":"Personalised therapy in follicular lymphoma - is the dial turning?","authors":"Kim M Linton,&nbsp;Lena Specht,&nbsp;Astrid Pavlovsky,&nbsp;Carrie A Thompson,&nbsp;Eva Kimby,&nbsp;Daphne de Jong,&nbsp;Loretta J Nastoupil,&nbsp;Anne-Ségolène Cottereau,&nbsp;Carla Casulo,&nbsp;Clémentine Sarkozy,&nbsp;Jessica Okosun","doi":"10.1002/hon.3205","DOIUrl":"https://doi.org/10.1002/hon.3205","url":null,"abstract":"<p><p>Follicular lymphoma is the most common indolent lymphoma accounting for approximately 20%-25% of all new non-Hodgkin lymphoma diagnoses in western countries. Whilst outcomes are mostly favorable, the spectrum of clinical phenotypes includes high-risk groups with significantly inferior outcomes. This review discusses recent updates in risk stratification and treatment approaches from upfront treatment for limited and advanced stage follicular lymphoma to the growing options for relapsed, refractory disease with perspectives on how to approach this from a personalized lens. Notable gaps remain on how one can precisely and prospectively select optimal treatment for patients based on varying risks, with an anticipation that an increased understanding of the biology of these different phenotypes and increasing refinement of imaging- and biomarker-based tools will, in time, allow these gaps to be closed.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10235264","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":"Recent updates in the indolent lymphomas: Update on marginal zone lymphoma and Waldenström's macroglobulinemia.","authors":"Karima Amaador,&nbsp;Catherine Thieblemont,&nbsp;Judith Trotman,&nbsp;Monique C Minnema","doi":"10.1002/hon.3210","DOIUrl":"https://doi.org/10.1002/hon.3210","url":null,"abstract":"<p><p>Marginal Zone Lymphoma (MZL) and Waldenström's Macroglobulinemia (WM) are indolent lymphomas that both arise from post germinal center lymphocytes. Both can secrete a monoclonal protein but high levels are mostly only seen in WM. The MYD88 L256P somatic mutation that is present in an estimated 95% of patients with WM has helped greatly in differentiating the two lymphomas. Several large clinical studies with new drugs have been performed that have provided new treatment options for both MZL and WM patients. In this short review we will discuss the recent literature published and provide some recommendations.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10202820","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 MAPK activation via mutations in NRAS, KRAS and BRAF on clinical outcome in newly diagnosed multiple myeloma","authors":"Camille Perroud,&nbsp;Dario Thurian,&nbsp;Martin Andres,&nbsp;Arnaud Künzi,&nbsp;Gertrud Wiedemann,&nbsp;Sacha Zeerleder,&nbsp;Ulrike Bacher,&nbsp;Thomas Pabst,&nbsp;Yara Banz,&nbsp;Naomi Porret,&nbsp;Ekaterina Rebmann","doi":"10.1002/hon.3208","DOIUrl":"10.1002/hon.3208","url":null,"abstract":"<p>Until now, next generation sequencing (NGS) data has not been incorporated into any prognostic stratification of multiple myeloma (MM) and no therapeutic considerations are based upon it. In this work, we correlated NGS data with (1) therapy response and survival parameters in newly diagnosed multiple myeloma, treated by VRd * and (2) MM disease stage: newly diagnosed multiple myeloma (ndMM) versus relapsed and/or refractory (relapsed/refractory multiple myeloma). We analyzed 126 patients, with ndMM and relapsed refractory multiple myeloma (rrMM), treated at the University Hospital of Bern (Inselspital). Next generation sequencing was performed on bone marrow, as part of routine diagnostics. The NGS panel comprised eight genes <i>CCND1</i>, <i>DIS3</i>, <i>EGR1</i>, <i>FAM4</i>6C <i>(TENT5C)</i>, <i>FGFR3</i>, <i>PRDM1</i>, <i>TP53</i>, <i>TRAF3</i> and seven hotspots in <i>BRAF</i>, <i>IDH1</i>, <i>IDH2</i>, <i>IRF4</i>, <i>KRAS</i>, <i>NRAS</i>. The primary endpoint was complete remission (CR) after VRd in ndMM, in correlation with mutational profile. Mutational load was generally higher in rrMM, with more frequently mutated <i>TP53</i>: 11/87 (13%) in ndMM versus 9/11 (81%) in rrMM (OR 0.0857, <i>p</i> = 0.0007). In ndMM, treated by VRd, mutations in MAPK-pathway members (<i>NRAS, KRAS</i> or <i>BRAF</i>) were associated with reduced probability of CR (21/38, 55%), as compared with <i>wild type NRAS, KRAS</i> or <i>BRAF</i> (34/40, 85%; OR 0.2225, <i>p</i> = 0.006). <i>NRAS</i> c.181C &gt; A (p.Q61K) as a single mutation event showed a trend to reduced probability of achieving CR (OR 0.0912, <i>p</i> = 0.0247). Activation of MAPK pathway via mutated <i>NRAS</i>, <i>KRAS</i> and <i>BRAF</i> genes seems to have a negative impact on outcome in ndMM patients receiving VRd therapy. VRd* - bortezomib (Velcade®), lenalidomide (Revlimid®) and dexamethasone.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3208","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9834357","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":"Dual combined antiviral treatment with remdesivir and nirmatrelvir/ritonavir in patients with impaired humoral immunity and persistent SARS-CoV-2 infection","authors":"Zeno Pasquini,&nbsp;Alice Toschi,&nbsp;Beatrice Casadei,&nbsp;Cinzia Pellegrini,&nbsp;Alessandra D’Abramo,&nbsp;Serena Vita,&nbsp;Alessia Beccacece,&nbsp;Linda Bussini,&nbsp;Maria Clara Chionsini,&nbsp;Nicola Dentale,&nbsp;Alessia Cantiani,&nbsp;Tiziana Lazzarotto,&nbsp;Michele Bartoletti,&nbsp;Emanuele Nicastri,&nbsp;Pierluigi Zinzani,&nbsp;Maddalena Giannella,&nbsp;Pierluigi Viale","doi":"10.1002/hon.3206","DOIUrl":"10.1002/hon.3206","url":null,"abstract":"<p>Despite global vaccination efforts, immunocompromized patients remain at high risk for COVID-19-associated morbidity. In particular, patients with impaired humoral immunity have shown a high risk of persistent infection. We report a case series of adult patients with B cell malignancies and/or undergoing B cell targeting therapies with persisting SARS-CoV-2 infection and treated with a combination antiviral therapy of remdesivir and nirmatrelvir/ritonavir, in three Italian tertiary academic hospitals. A total of 14 patients with impaired adaptive humoral immunity and prolonged SARS-CoV-2 infection were treated with the dual antiviral therapy. The median age was 60 (IQR 56–68) years, and 11 were male. Twelve patients had B cell lymphoma, one patient had chronic lymphocytic leukemia and one patient had multiple sclerosis. Thirteen out of 14 patients had received prior B cell-targeting therapies, consisting of anti-CD20 monoclonal antibodies in 11 patients, and chimeric antigen receptor T therapy in 2 patients. The median time between diagnosis and therapy start was 42.0 (IQR 35–46) days. Seven patients had mild, 6 moderate and one severe disease. Nine patients had signs of interstitial pneumonitis on chest computed tomography scans before treatment. The median duration of nirmatrelvir/ritonavir and remdesivir combination therapy was 10 days. All patients showed resolution of COVID-19-related symptoms after a median of 6 (IQR 4–11) days and viral clearance after 9 (IQR 5–11) days. Combination therapy with remdesivir and nirmatrelvir/ritonavir is a promising treatment option for persistent COVID-19 in immunocompromized patients with humoral immunity impairment, worthy of prospective comparative trials.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3206","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9834352","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}