Vittorio Ruggero Zilioli, Emanuele Cencini, Sonya De Lorenzo, Luca Pezzullo, Michele Merli, Flavia Rivellini, Cristina Muzi, Barbieri Emiliano, Luigi Marcheselli, Stefano Luminari. Real-life study on the use of response adapted therapy in patients with Hodgkin Lymphoma: Results from a multicenter experience. Hematol Oncol. 2023;42(3):e3273. https://doi.org/10.1002/hon.3273.
In the article, affiliation 9 is not correct. The correct affiliation is “Hematology, Azienda Unità Sanitaria Locale - IRCCS of Reggio Emilia, Reggio Emilia, Italy”.
We apologize for this error.
Vittorio Ruggero Zilioli, Emanuele Cencini, Sonya De Lorenzo, Luca Pezzullo, Michele Merli, Flavia Rivellini, Cristina Muzi, Barbieri Emiliano, Luigi Marcheselli, Stefano Luminari.霍奇金淋巴瘤患者使用反应适应疗法的实际研究:来自多中心经验的结果。Hematol Oncol.2023;42(3):e3273。https://doi.org/10.1002/hon.3273.In,文章中的隶属关系9不正确。正确的单位是 "Hematology, Azienda Unità Sanitaria Locale - IRCCS of Reggio Emilia, Reggio Emilia, Italy"。我们对此错误表示歉意。
{"title":"Correction to Real-life study on the use of response adapted therapy in patients with Hodgkin Lymphoma: Results from a multicenter experience","authors":"","doi":"10.1002/hon.3291","DOIUrl":"10.1002/hon.3291","url":null,"abstract":"<p>Vittorio Ruggero Zilioli, Emanuele Cencini, Sonya De Lorenzo, Luca Pezzullo, Michele Merli, Flavia Rivellini, Cristina Muzi, Barbieri Emiliano, Luigi Marcheselli, Stefano Luminari. Real-life study on the use of response adapted therapy in patients with Hodgkin Lymphoma: Results from a multicenter experience. Hematol Oncol. 2023;42(3):e3273. https://doi.org/10.1002/hon.3273.</p><p>In the article, affiliation 9 is not correct. The correct affiliation is “Hematology, Azienda Unità Sanitaria Locale - IRCCS of Reggio Emilia, Reggio Emilia, Italy”.</p><p>We apologize for this error.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3291","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305768","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}
Hanyin Wang, Shulan Tian, Charla R. Secreto, Sutapa Sinha, Min Shi, Timothy Call, Yucai Wang, Sameer A. Parikh, Saad S. Kenderian, Rong He, Jose F. Leis, Daniel L. VanDyke, Eric W. Klee, Susan L. Slager, Esteban Braggio, Huihuang Yan, Wei Ding
{"title":"Clonal dynamics of Richter transformation in chronic lymphocytic leukemia","authors":"Hanyin Wang, Shulan Tian, Charla R. Secreto, Sutapa Sinha, Min Shi, Timothy Call, Yucai Wang, Sameer A. Parikh, Saad S. Kenderian, Rong He, Jose F. Leis, Daniel L. VanDyke, Eric W. Klee, Susan L. Slager, Esteban Braggio, Huihuang Yan, Wei Ding","doi":"10.1002/hon.3282","DOIUrl":"10.1002/hon.3282","url":null,"abstract":"","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293340","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}
Mogamulizumab is a humanized antibody targeting CC chemokine receptor 4 (CCR4). This post-marketing surveillance was conducted in Japan as a regulatory requirement from 2014 to 2020 to ensure the safety and effectiveness of mogamulizumab in patients with relapsed or refractory (r/r) CCR4-positive peripheral T-cell lymphoma (PTCL) or r/r cutaneous T-cell lymphoma (CTCL). Safety and effectiveness data were collected for up to 31 weeks after treatment initiation. A total of 142 patients were registered; safety was evaluated in 136 patients. The median number of doses was 8.0 (range, 1–18). The main reasons for treatment termination were insufficient response (22.1%) and adverse events (13.2%). The frequency of any grade adverse drug reaction was 57.4%, including skin disorders (26.5%), infections and immune system disorders (16.2%), and infusion-related reactions (13.2%). Graft-versus-host disease, grade 2, developed in one of two patients who underwent allogeneic-hematopoietic stem cell transplantation after receiving mogamulizumab. Effectiveness was evaluated in 131 patients (103 with PTCL; 28 with CTCL). The best overall response rate was 45.8% (PTCL, 47.6%; CTCL, 39.3%). At week 31, the survival rate was 69.0% (95% confidence interval, 59.8%–76.5%) [PTCL, 64.4% (54.0%–73.0%); CTCL, 90.5% (67.0%–97.5%)]. Safety and effectiveness were comparable between patients <70 and ≥ 70 years old and between those with relapsed and refractory disease. The safety and effectiveness of mogamulizumab for PTCL and CTCL in the real world were comparable with the data reported in previous clinical trials.
{"title":"Safety and effectiveness of mogamulizumab in relapsed or refractory CC chemokine receptor 4-positive peripheral T-cell lymphoma and relapsed or refractory cutaneous T-cell lymphoma: A post-marketing surveillance in Japan","authors":"Kenji Ishitsuka, Tomoharu Yasukawa, Yukie Tsuji","doi":"10.1002/hon.3292","DOIUrl":"10.1002/hon.3292","url":null,"abstract":"<p>Mogamulizumab is a humanized antibody targeting CC chemokine receptor 4 (CCR4). This post-marketing surveillance was conducted in Japan as a regulatory requirement from 2014 to 2020 to ensure the safety and effectiveness of mogamulizumab in patients with relapsed or refractory (r/r) CCR4-positive peripheral T-cell lymphoma (PTCL) or r/r cutaneous T-cell lymphoma (CTCL). Safety and effectiveness data were collected for up to 31 weeks after treatment initiation. A total of 142 patients were registered; safety was evaluated in 136 patients. The median number of doses was 8.0 (range, 1–18). The main reasons for treatment termination were insufficient response (22.1%) and adverse events (13.2%). The frequency of any grade adverse drug reaction was 57.4%, including skin disorders (26.5%), infections and immune system disorders (16.2%), and infusion-related reactions (13.2%). Graft-versus-host disease, grade 2, developed in one of two patients who underwent allogeneic-hematopoietic stem cell transplantation after receiving mogamulizumab. Effectiveness was evaluated in 131 patients (103 with PTCL; 28 with CTCL). The best overall response rate was 45.8% (PTCL, 47.6%; CTCL, 39.3%). At week 31, the survival rate was 69.0% (95% confidence interval, 59.8%–76.5%) [PTCL, 64.4% (54.0%–73.0%); CTCL, 90.5% (67.0%–97.5%)]. Safety and effectiveness were comparable between patients <70 and ≥ 70 years old and between those with relapsed and refractory disease. The safety and effectiveness of mogamulizumab for PTCL and CTCL in the real world were comparable with the data reported in previous clinical trials.</p><p>Clinical Trial Registration</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3292","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283539","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}
Bruton's tyrosine kinase (BTK) inhibitors have revolutionized the treatment of B-cell malignancies. They target BTK, a key effector in the B-cell receptor (BCR) signaling pathway, crucial for B-cell survival and proliferation. The first-in-class irreversible BTK inhibitor, ibrutinib, was approved for various B-cell malignancies but has limitations due to off-target effects. Second-generation inhibitors, such as acalabrutinib and zanubrutinib, offer improved selectivity and reduced side effects. However, resistance to BTK inhibitors, driven by BTK mutations, remains a challenge. Combinatorial therapies with PI3K inhibitors, immune checkpoint inhibitors, BH3 mimetics, and anti-CD20 antibodies show promise in overcoming resistance. Noncovalent BTK inhibitors and proteolysis-targeting chimeras (PROTACs) are emerging strategies with potential to combat resistance. Overall, advancements in BTK-targeted therapies provide hope for improved outcomes in patients with B-cell malignancies and a promising avenue to address drug resistance. Further research is needed to optimize combination therapies and identify optimal treatment regimens.
布鲁顿酪氨酸激酶(BTK)抑制剂彻底改变了B细胞恶性肿瘤的治疗方法。BTK是B细胞受体(BCR)信号通路中的一个关键效应因子,对B细胞的存活和增殖至关重要。第一类不可逆 BTK 抑制剂依鲁替尼已获准用于治疗各种 B 细胞恶性肿瘤,但由于其脱靶效应,该药的疗效存在局限性。第二代抑制剂,如阿卡布替尼和扎努布替尼,提高了选择性并减少了副作用。然而,BTK 基因突变导致的对 BTK 抑制剂的耐药性仍然是一个挑战。PI3K抑制剂、免疫检查点抑制剂、BH3模拟物和抗CD20抗体的组合疗法有望克服耐药性。非共价BTK抑制剂和蛋白水解靶向嵌合体(PROTACs)是新兴的策略,具有对抗耐药性的潜力。总之,BTK 靶向疗法的进步为改善 B 细胞恶性肿瘤患者的治疗效果带来了希望,也为解决耐药性问题提供了一条前景广阔的途径。优化联合疗法和确定最佳治疗方案还需要进一步的研究。
{"title":"Strategies for overcoming resistance to Bruton's tyrosine kinase inhibitor zanubrutinib","authors":"Hana Dostálová, Vladimír Kryštof","doi":"10.1002/hon.3294","DOIUrl":"10.1002/hon.3294","url":null,"abstract":"<p>Bruton's tyrosine kinase (BTK) inhibitors have revolutionized the treatment of B-cell malignancies. They target BTK, a key effector in the B-cell receptor (BCR) signaling pathway, crucial for B-cell survival and proliferation. The first-in-class irreversible BTK inhibitor, ibrutinib, was approved for various B-cell malignancies but has limitations due to off-target effects. Second-generation inhibitors, such as acalabrutinib and zanubrutinib, offer improved selectivity and reduced side effects. However, resistance to BTK inhibitors, driven by BTK mutations, remains a challenge. Combinatorial therapies with PI3K inhibitors, immune checkpoint inhibitors, BH3 mimetics, and anti-CD20 antibodies show promise in overcoming resistance. Noncovalent BTK inhibitors and proteolysis-targeting chimeras (PROTACs) are emerging strategies with potential to combat resistance. Overall, advancements in BTK-targeted therapies provide hope for improved outcomes in patients with B-cell malignancies and a promising avenue to address drug resistance. Further research is needed to optimize combination therapies and identify optimal treatment regimens.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3294","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283540","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}
Claudia Bellofiore, Pietro Benvenuti, Roberto Mina, Marco Basset, Andrea Foli, Martina Nanci, Mario Nuvolone, Gianluigi Guida, Andrea Attanasio, Roberta Mussinelli, Silvia Mangiacavalli, Claudio Salvatore Cartia, Valeria Masoni, Michele Palumbo, Lorenzo Cani, Stefania Oliva, Ugo Consoli, Concetta Conticello, Francesco Di Raimondo, Luca Arcaini, Sara Bringhen, Giampaolo Merlini, Giovanni Palladini, Paolo Milani
Daratumumab-based regimens are the new standard of care for newly diagnosed patients with AL amyloidosis based on the results of the ANDROMEDA study. However, real-world data on daratumumab efficacy in upfront therapy in unselected patients are scanty. In the framework of a prospective observational study, we investigated the efficacy and safety of daratumumab in 88 newly diagnosed patients, including subjects with IIIb cardiac stage (26%) or myeloma defining events (29%). Daratumumab was administered with bortezomib in 50 (56%) patients, lenalidomide in 31 (35%), and monotherapy in 7 (8%). The rate of serious adverse events was low (16%). The overall hematologic response rate was 75% with 52 (59%) patients attaining at least a very good partial response (VGPR) at six months. Amongst patients evaluable for organ response, the rate of cardiac and renal responses at 6 months was 31% and 21%, respectively. Comparing stage IIIb patients with the remaining ones, the rate of profound hematologic response was not significantly different (≥VGPR 57% vs. 59%, p 0.955) likewise the rate of cardiac (33% vs. 30%, p 0.340) and renal (40% vs. 16%, p 0.908) responses. Daratumumab-based regimens demonstrated to be safe and effective in treatment-naïve AL amyloidosis even in advanced stage disease.
根据ANDROMEDA研究的结果,以达拉单抗为基础的治疗方案是新诊断的AL淀粉样变性患者的新治疗标准。然而,有关达拉土单抗在未入选患者前期治疗中疗效的真实世界数据并不多。在一项前瞻性观察研究的框架内,我们调查了达拉单抗在88例新诊断患者中的疗效和安全性,其中包括IIIb心脏分期(26%)或骨髓瘤定义事件(29%)的受试者。达拉atumumab与硼替佐米联合用药的患者有50例(56%),来那度胺联合用药的患者有31例(35%),单药治疗的患者有7例(8%)。严重不良反应发生率较低(16%)。总体血液学反应率为75%,其中52例(59%)患者在6个月时至少获得了很好的部分反应(VGPR)。在可评估器官反应的患者中,6 个月时心脏和肾脏反应率分别为 31% 和 21%。将IIIb期患者与其余患者进行比较,血液学深度反应率(≥VGPR 57% vs. 59%,P 0.955)与心脏反应率(33% vs. 30%,P 0.340)和肾脏反应率(40% vs. 16%,P 0.908)无显著差异。即使是晚期AL淀粉样变性病,基于达拉土单抗的治疗方案也被证明对治疗无效的AL淀粉样变性病安全有效。
{"title":"A real-life study of daratumumab combinations in newly diagnosed patients with light chain (AL) amyloidosis","authors":"Claudia Bellofiore, Pietro Benvenuti, Roberto Mina, Marco Basset, Andrea Foli, Martina Nanci, Mario Nuvolone, Gianluigi Guida, Andrea Attanasio, Roberta Mussinelli, Silvia Mangiacavalli, Claudio Salvatore Cartia, Valeria Masoni, Michele Palumbo, Lorenzo Cani, Stefania Oliva, Ugo Consoli, Concetta Conticello, Francesco Di Raimondo, Luca Arcaini, Sara Bringhen, Giampaolo Merlini, Giovanni Palladini, Paolo Milani","doi":"10.1002/hon.3289","DOIUrl":"10.1002/hon.3289","url":null,"abstract":"<p>Daratumumab-based regimens are the new standard of care for newly diagnosed patients with AL amyloidosis based on the results of the ANDROMEDA study. However, real-world data on daratumumab efficacy in upfront therapy in unselected patients are scanty. In the framework of a prospective observational study, we investigated the efficacy and safety of daratumumab in 88 newly diagnosed patients, including subjects with IIIb cardiac stage (26%) or myeloma defining events (29%). Daratumumab was administered with bortezomib in 50 (56%) patients, lenalidomide in 31 (35%), and monotherapy in 7 (8%). The rate of serious adverse events was low (16%). The overall hematologic response rate was 75% with 52 (59%) patients attaining at least a very good partial response (VGPR) at six months. Amongst patients evaluable for organ response, the rate of cardiac and renal responses at 6 months was 31% and 21%, respectively. Comparing stage IIIb patients with the remaining ones, the rate of profound hematologic response was not significantly different (≥VGPR 57% vs. 59%, <i>p</i> 0.955) likewise the rate of cardiac (33% vs. 30%, <i>p</i> 0.340) and renal (40% vs. 16%, <i>p</i> 0.908) responses. Daratumumab-based regimens demonstrated to be safe and effective in treatment-naïve AL amyloidosis even in advanced stage disease.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185878","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}
Enrica Antonia Martino, Salvatore Palmieri, Monica Galli, Daniele Derudas, Roberto Mina, Roberta Della Pepa, Renato Zambello, Ernesto Vigna, Antonella Bruzzese, Silvia Mangiacavalli, Elena Zamagni, Catello Califano, Maurizio Musso, Concetta Conticello, Claudio Cerchione, Giuseppe Mele, Nicola Di Renzo, Massimo Offidani, Giuseppe Tarantini, Gloria Margiotta Casaluci, Angela Rago, Roberto Ria, Giuseppina Uccello, Gregorio Barilà, Gaetano Palumbo, Loredana Pettine, Iolanda Donatella Vincelli, Marino Brunori, Fabrizio Accardi, Valeria Amico, Angela Amendola, Raffaele Fontana, Velia Bongarzoni, Bernardo Rossini, Emilia Cotzia, Alessandro Gozzetti, Rita Rizzi, Nicola Sgherza, Giovanni Reddiconto, Antonio Maroccia, Luca Franceschini, Giuseppe Bertuglia, Davide Nappi, Emiliano Barbieri, Barbara Gamberi, Maria Teresa Petrucci, Francesco Di Raimondo, Antonino Neri, Fortunato Morabito, Pellegrino Musto, Massimo Gentile
The ELOQUENT-3 trial demonstrated the superiority of the combination of elotuzumab, pomalidomide, and dexamethasone (EloPd) in terms of efficacy and safety, compared to Pd in relapsed/refractory multiple myeloma (RRMM), who had received at least two prior therapies, including lenalidomide and a proteasome inhibitor. The present study is an 18-month follow-up update of a previously published Italian real-life RRMM cohort of patients treated with EloPd. This revised analysis entered 319 RRMM patients accrued in 41 Italian centers. After a median follow-up of 17.7 months, 213 patients (66.4%) experienced disease progression or died. Median progression-free survival (PFS) and overall survival (OS) were 7.5 and 19.2 months, respectively. The updated multivariate analysis showed a significant reduction of PFS benefit magnitude both in advanced International Staging System (ISS) (II and III) stages and previous exposure to daratumumab cases. Instead, advanced ISS (II and III) stages and more than 2 previous lines of therapy maintained an independent prognostic impact on OS. Major adverse events included grade three-fourths neutropenia (24.9%), anemia (13.4%), lymphocytopenia (15.5%), and thrombocytopenia (10.7%), while infection rates and pneumonia were 19.3% and 8.7%, respectively. A slight increase in the incidence of neutropenia and lymphocytopenia was registered with longer follow-up. In conclusion, our real-world study still confirms that EloPd is a safe and possible therapeutic choice for RRMM. Nevertheless, novel strategies are desirable for those patients exposed to daratumumab.
{"title":"Elotuzumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended follow-up of a multicenter, retrospective real-world experience with 321 cases outside of controlled clinical trials","authors":"Enrica Antonia Martino, Salvatore Palmieri, Monica Galli, Daniele Derudas, Roberto Mina, Roberta Della Pepa, Renato Zambello, Ernesto Vigna, Antonella Bruzzese, Silvia Mangiacavalli, Elena Zamagni, Catello Califano, Maurizio Musso, Concetta Conticello, Claudio Cerchione, Giuseppe Mele, Nicola Di Renzo, Massimo Offidani, Giuseppe Tarantini, Gloria Margiotta Casaluci, Angela Rago, Roberto Ria, Giuseppina Uccello, Gregorio Barilà, Gaetano Palumbo, Loredana Pettine, Iolanda Donatella Vincelli, Marino Brunori, Fabrizio Accardi, Valeria Amico, Angela Amendola, Raffaele Fontana, Velia Bongarzoni, Bernardo Rossini, Emilia Cotzia, Alessandro Gozzetti, Rita Rizzi, Nicola Sgherza, Giovanni Reddiconto, Antonio Maroccia, Luca Franceschini, Giuseppe Bertuglia, Davide Nappi, Emiliano Barbieri, Barbara Gamberi, Maria Teresa Petrucci, Francesco Di Raimondo, Antonino Neri, Fortunato Morabito, Pellegrino Musto, Massimo Gentile","doi":"10.1002/hon.3290","DOIUrl":"10.1002/hon.3290","url":null,"abstract":"<p>The ELOQUENT-3 trial demonstrated the superiority of the combination of elotuzumab, pomalidomide, and dexamethasone (EloPd) in terms of efficacy and safety, compared to Pd in relapsed/refractory multiple myeloma (RRMM), who had received at least two prior therapies, including lenalidomide and a proteasome inhibitor. The present study is an 18-month follow-up update of a previously published Italian real-life RRMM cohort of patients treated with EloPd. This revised analysis entered 319 RRMM patients accrued in 41 Italian centers. After a median follow-up of 17.7 months, 213 patients (66.4%) experienced disease progression or died. Median progression-free survival (PFS) and overall survival (OS) were 7.5 and 19.2 months, respectively. The updated multivariate analysis showed a significant reduction of PFS benefit magnitude both in advanced International Staging System (ISS) (II and III) stages and previous exposure to daratumumab cases. Instead, advanced ISS (II and III) stages and more than 2 previous lines of therapy maintained an independent prognostic impact on OS. Major adverse events included grade three-fourths neutropenia (24.9%), anemia (13.4%), lymphocytopenia (15.5%), and thrombocytopenia (10.7%), while infection rates and pneumonia were 19.3% and 8.7%, respectively. A slight increase in the incidence of neutropenia and lymphocytopenia was registered with longer follow-up. In conclusion, our real-world study still confirms that EloPd is a safe and possible therapeutic choice for RRMM. Nevertheless, novel strategies are desirable for those patients exposed to daratumumab.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179587","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}
Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease that requires personalized clinical treatment. Assigning patients to different risk categories and cytogenetic abnormality and genetic mutation groups has been widely applied for prognostic stratification of DLBCL. Increasing evidence has demonstrated that dysregulated metabolic processes contribute to the initiation and progression of DLBCL. Metabolic competition within the tumor microenvironment is also known to influence immune cell metabolism. However, metabolism- and immune-related stratification has not been established. Here, 1660 genes involved in 84 metabolic pathways were selected and tested to establish metabolic clusters (MECs) of DLBCL. MECs established based on independent lymphoma datasets distinguished different survival outcomes. The CIBERSORT algorithm and EcoTyper were applied to quantify the relative abundance of immune cell types and identify variation in cell states for 13 lineages comprising the tumor micro environment among different MECs, respectively. Functional characterization showed that MECs were an indicator of the immune microenvironment and correlated with distinctive mutational characteristics and oncogenic signaling pathways. The novel immune-related MECs exhibited promising clinical prognostic value and potential for informing DLBCL treatment decisions.
{"title":"Metabolic pathway-based subtyping reveals distinct microenvironmental states associated with diffuse large B-cell lymphoma outcomes","authors":"Xiaohui Wang, Hengqi Liu, Yue Fei, Zheng Song, Xiangrui Meng, Jingwei Yu, Xia Liu, Lanfang Li, Lihua Qiu, Zhengzi Qian, Shiyong Zhou, Xianhuo Wang, Huilai Zhang","doi":"10.1002/hon.3279","DOIUrl":"10.1002/hon.3279","url":null,"abstract":"<p>Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease that requires personalized clinical treatment. Assigning patients to different risk categories and cytogenetic abnormality and genetic mutation groups has been widely applied for prognostic stratification of DLBCL. Increasing evidence has demonstrated that dysregulated metabolic processes contribute to the initiation and progression of DLBCL. Metabolic competition within the tumor microenvironment is also known to influence immune cell metabolism. However, metabolism- and immune-related stratification has not been established. Here, 1660 genes involved in 84 metabolic pathways were selected and tested to establish metabolic clusters (MECs) of DLBCL. MECs established based on independent lymphoma datasets distinguished different survival outcomes. The CIBERSORT algorithm and EcoTyper were applied to quantify the relative abundance of immune cell types and identify variation in cell states for 13 lineages comprising the tumor micro environment among different MECs, respectively. Functional characterization showed that MECs were an indicator of the immune microenvironment and correlated with distinctive mutational characteristics and oncogenic signaling pathways. The novel immune-related MECs exhibited promising clinical prognostic value and potential for informing DLBCL treatment decisions.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179607","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}
María Turos-Cabal, Ana M. Sánchez-Sánchez, Noelia Puente-Moncada, Federico Herrera, Isaac Antolin, Carmen Rodríguez, Vanesa Martín
The FLT3-ITD mutation represents the most frequent genetic alteration in newly diagnosed acute myeloid leukemia (AML) patient and is associated with poor prognosis. Mutation result in the retention of a constitutively active form of this receptor in the endoplasmic reticulum (ER) and the subsequent modification of its downstream effectors. Here, we assessed the impact of such retention on ER homeostasis and found that mutant cells present lower levels of ER stress due to the overexpression of ERO1α, one of the main proteins of the protein folding machinery at the ER. Overexpression of ERO1α resulted essential for ITD mutant cells survival and chemoresistance and also played a crucial role in shaping the type of glucose metabolism in AML cells, being the mitochondrial pathway the predominant one in those with a higher ER stress (non-mutated cells) and the glycolytic pathway the predominant one in those with lower ER stress (mutated cells). Our data indicate that FLT3 mutational status dictates the route for glucose metabolism in an ERO1α depending on manner and this provides a survival advantage to tumors carrying these ITD mutations.
{"title":"FLT3-ITD regulation of the endoplasmic reticulum functions in acute myeloid leukemia","authors":"María Turos-Cabal, Ana M. Sánchez-Sánchez, Noelia Puente-Moncada, Federico Herrera, Isaac Antolin, Carmen Rodríguez, Vanesa Martín","doi":"10.1002/hon.3281","DOIUrl":"10.1002/hon.3281","url":null,"abstract":"<p>The FLT3-ITD mutation represents the most frequent genetic alteration in newly diagnosed acute myeloid leukemia (AML) patient and is associated with poor prognosis. Mutation result in the retention of a constitutively active form of this receptor in the endoplasmic reticulum (ER) and the subsequent modification of its downstream effectors. Here, we assessed the impact of such retention on ER homeostasis and found that mutant cells present lower levels of ER stress due to the overexpression of ERO1α, one of the main proteins of the protein folding machinery at the ER. Overexpression of ERO1α resulted essential for ITD mutant cells survival and chemoresistance and also played a crucial role in shaping the type of glucose metabolism in AML cells, being the mitochondrial pathway the predominant one in those with a higher ER stress (non-mutated cells) and the glycolytic pathway the predominant one in those with lower ER stress (mutated cells). Our data indicate that FLT3 mutational status dictates the route for glucose metabolism in an ERO1α depending on manner and this provides a survival advantage to tumors carrying these ITD mutations.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3281","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075637","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}
Anna Panovská, Pavel Žák, Tereza Jurková, Tomáš Arpáš, Yvona Brychtová, Alžběta Vašíková, Viera Hrabčáková, Adéla Prchlíková, Martina Filipová, Michael Doubek
Hairy cell leukemia (HCL) and HCL-like disorders have to be distinguished because of their different biology and treatment response. Thus, we conducted a retrospective study on patients with HCL and hairy cell leukemia variant (HCLv) to assess diagnostic algorithms and treatment outcomes in a real-world setting. We analyzed 225 HCL and 26 HCLv patients with median follow-up of 67.9 months (HCL) and 20.1 months (HCLv). Median age at diagnosis was 56.2 (HCL) and 69.5 years (HCLv), male predominance was observed in both groups (76.0% vs. 73.1%). Diagnostics was mostly based on morphological evidence of hairy cells in the peripheral blood and bone marrow. At diagnosis, BRAFV600E mutation was detected in 94.7% of examined HCL patients and in no HCLv patient. Front-line treatment was indicated in 205 (91.1%) HCL and 18 (69.2%) HCLv patients. The majority of HCL patients were administered a cladribine-based regimen (91.2%). Overall response rate (ORR) was higher in cladribine-treated patients compared to those given other treatments (97.7% vs. 81.3%), the same applied with achieving Complete remission (CR) (91.2% vs. 62.5%). HCLv treatment was heterogeneous, but cladribine remained the most frequent option (44.4%) with ORR 81.3% and CR rates 43.8%. Second-line treatment was indicated in 52 HCL and 8 HCLv patients, 25.4% and 44.4% of those treated in first-line. In the whole HCL group, median time to next treatment (TTNT) was not reached and 10-year TTNT was estimated at 74.1%. HCLv patients who underwent first-line treatment had a median TTNT of 56 months. The median overall survival (OS) in HCL patients was not reached compared to HCLv with a median OS of 9.5 years. These data confirm an excellent prognosis for HCL patients treated with cladribine-based therapy. On the contrary, HCLv with its aggressive behavior represents a group of patients in whom novel treatment approaches are needed.
{"title":"Real-world data on diagnostics, treatment and outcomes of patients with hairy cell leukemia: The HCL-CLLEAR study","authors":"Anna Panovská, Pavel Žák, Tereza Jurková, Tomáš Arpáš, Yvona Brychtová, Alžběta Vašíková, Viera Hrabčáková, Adéla Prchlíková, Martina Filipová, Michael Doubek","doi":"10.1002/hon.3280","DOIUrl":"10.1002/hon.3280","url":null,"abstract":"<p>Hairy cell leukemia (HCL) and HCL-like disorders have to be distinguished because of their different biology and treatment response. Thus, we conducted a retrospective study on patients with HCL and hairy cell leukemia variant (HCLv) to assess diagnostic algorithms and treatment outcomes in a real-world setting. We analyzed 225 HCL and 26 HCLv patients with median follow-up of 67.9 months (HCL) and 20.1 months (HCLv). Median age at diagnosis was 56.2 (HCL) and 69.5 years (HCLv), male predominance was observed in both groups (76.0% vs. 73.1%). Diagnostics was mostly based on morphological evidence of hairy cells in the peripheral blood and bone marrow. At diagnosis, <i>BRAF</i> <i>V6</i>00E mutation was detected in 94.7% of examined HCL patients and in no HCLv patient. Front-line treatment was indicated in 205 (91.1%) HCL and 18 (69.2%) HCLv patients. The majority of HCL patients were administered a cladribine-based regimen (91.2%). Overall response rate (ORR) was higher in cladribine-treated patients compared to those given other treatments (97.7% vs. 81.3%), the same applied with achieving Complete remission (CR) (91.2% vs. 62.5%). HCLv treatment was heterogeneous, but cladribine remained the most frequent option (44.4%) with ORR 81.3% and CR rates 43.8%. Second-line treatment was indicated in 52 HCL and 8 HCLv patients, 25.4% and 44.4% of those treated in first-line. In the whole HCL group, median time to next treatment (TTNT) was not reached and 10-year TTNT was estimated at 74.1%. HCLv patients who underwent first-line treatment had a median TTNT of 56 months. The median overall survival (OS) in HCL patients was not reached compared to HCLv with a median OS of 9.5 years. These data confirm an excellent prognosis for HCL patients treated with cladribine-based therapy. On the contrary, HCLv with its aggressive behavior represents a group of patients in whom novel treatment approaches are needed.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3280","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916152","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}
Kaitlin Annunzio, Subodh Bhatta, Walter Hanel, Qiuhong Zhao, Mackenzie Owen, Havi Rosen, Timothy J. Voorhees, David A. Bond, Yazeed Sawalha, Audrey M. Sigmund, Lapo Alinari, Robert A. Baiocchi, Kami J. Maddocks, Daniel Jones, Beth Christian, Narendranath Epperla
Follicular lymphoma (FL) is the most common indolent B-cell non-Hodgkin lymphoma. Circulating lymphoma (CL) cells can be seen at diagnosis in some FL patients, however, previous studies evaluating this have shown mixed results. Therefore, we sought to evaluate the impact of CL at diagnosis on outcomes in patients with newly diagnosed FL using data from a single center. Patients were divided into CL+ and CL− based on immunophenotyping via peripheral blood (PB) flow cytometry. CL was defined as detectable clonally restricted B-cells that matched the actual or expected B-cell immunophenotype of FL. The primary endpoint was progression-free survival (PFS) after first-line treatment and secondary endpoints included overall response rate (ORR), overall survival (OS), diagnosis to treatment interval (DTI), progression of disease within 2 years of diagnosis (POD24), and cumulative incidence of transformation between the two groups. Among the 541 patients with FL, 204 had PB flow cytometry performed at diagnosis, and after excluding patients not meeting the eligibility criteria, 147 cases remained with 24 (16%) CL+ at diagnosis. Patients in the CL+ group were younger (53 vs. 58 years, p = 0.02), had more extranodal involvement (83% vs. 44%, p < 0.01), follicular lymphoma international prognostic index 3–5 (55% vs. 31%, p = 0.01), and a higher proportion received first-line immunochemotherapy (75% vs. 43%, p = 0.01) compared to the CL−group. The median PFS was not significantly different between CL+ (6.27 years, 95% CI = 3.61-NR) and CL− (6.61 years, 95% CI = 5.10–9.82) cohorts regardless of the first-line treatment or level of absolute PB CL cells. There was no significant difference in ORR, median OS, DTI, POD24, and cumulative incidence of transformation between the two groups. In our study, we found that the presence of CL cells at diagnosis in FL in the contemporary era did not impact outcomes and survival.
{"title":"Prognostic relevance of circulating lymphoma cells at diagnosis in newly diagnosed follicular lymphoma patients","authors":"Kaitlin Annunzio, Subodh Bhatta, Walter Hanel, Qiuhong Zhao, Mackenzie Owen, Havi Rosen, Timothy J. Voorhees, David A. Bond, Yazeed Sawalha, Audrey M. Sigmund, Lapo Alinari, Robert A. Baiocchi, Kami J. Maddocks, Daniel Jones, Beth Christian, Narendranath Epperla","doi":"10.1002/hon.3278","DOIUrl":"10.1002/hon.3278","url":null,"abstract":"<p>Follicular lymphoma (FL) is the most common indolent B-cell non-Hodgkin lymphoma. Circulating lymphoma (CL) cells can be seen at diagnosis in some FL patients, however, previous studies evaluating this have shown mixed results. Therefore, we sought to evaluate the impact of CL at diagnosis on outcomes in patients with newly diagnosed FL using data from a single center. Patients were divided into CL+ and CL− based on immunophenotyping via peripheral blood (PB) flow cytometry. CL was defined as detectable clonally restricted B-cells that matched the actual or expected B-cell immunophenotype of FL. The primary endpoint was progression-free survival (PFS) after first-line treatment and secondary endpoints included overall response rate (ORR), overall survival (OS), diagnosis to treatment interval (DTI), progression of disease within 2 years of diagnosis (POD24), and cumulative incidence of transformation between the two groups. Among the 541 patients with FL, 204 had PB flow cytometry performed at diagnosis, and after excluding patients not meeting the eligibility criteria, 147 cases remained with 24 (16%) CL+ at diagnosis. Patients in the CL+ group were younger (53 vs. 58 years, <i>p</i> = 0.02), had more extranodal involvement (83% vs. 44%, <i>p</i> < 0.01), follicular lymphoma international prognostic index 3–5 (55% vs. 31%, <i>p</i> = 0.01), and a higher proportion received first-line immunochemotherapy (75% vs. 43%, <i>p</i> = 0.01) compared to the CL−group. The median PFS was not significantly different between CL+ (6.27 years, 95% CI = 3.61-NR) and CL− (6.61 years, 95% CI = 5.10–9.82) cohorts regardless of the first-line treatment or level of absolute PB CL cells. There was no significant difference in ORR, median OS, DTI, POD24, and cumulative incidence of transformation between the two groups. In our study, we found that the presence of CL cells at diagnosis in FL in the contemporary era did not impact outcomes and survival.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897880","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}