Wei-Ying Jen, Jennifer Croden, Emmanuel Almanza-Huante, Courtney DiNardo, Kelly Chien, Danielle Hammond, Wei Qiao, Yesid Alvarado, Lucia Masarova, Andres E. Quesada, Sherry Pierce, Alex Bataller, Guillermo Garcia-Manero, Amin Alousi, Nicholas Short, Naval Daver, Farhad Ravandi, Hagop Kantarjian, Tapan M. Kadia
Venetoclax has been combined with intensive chemotherapy regimens in the treatment of acute myeloid leukemia (AML). We aimed to investigate the safety and efficacy of venetoclax combined with full-dose CPX-351 (CPX + VEN) in newly diagnosed (ND) AML. Seventeen patients with a median age of 59 years (range, 43–69) were treated; 71% had secondary AML, 47% had prior hypomethylating agent (HMA) exposure, 59% had myelodysplastic syndrome (MDS)-related (MR) mutations, 47% had complex karyotype, and 29% were TP53 mutated. The overall response rate (ORR) was 82% (95% CI, 57–96) with a composite complete remission rate (CRc) of 71% (95% CI, 50–93). Patients with MR mutations had an ORR of 100% (95% CI, 69–100), including a CRc of 90% (95% CI, 55–100). Patients with prior HMA exposure had a CRc of 63% (95% CI, 24–91). With a median follow-up time of 11.8 months, the median overall survival (OS) was 12.8 months (95% CI, 5–NE) with a 2-year OS of 34% (95% CI, 10–61). Patients with MR mutations had a median OS of 17.9 months versus 5.1 months in patients without MR mutations (P = 0.039). Twelve (86%) of 14 responding patients proceeded to stem cell transplant (SCT); the median recurrence-free survival and OS landmarked from date of SCT were 14.7 months (95% CI, 1–32) and 14.7 months (95% CI, 4–25), respectively. The 4-week mortality was 0% and the 8-week mortality was 17%. The most common adverse events were related to myelosuppression. CPX + VEN resulted in high remission rates and enabled progression to allogenic SCT for the majority of a highly adverse group of ND AML patients.
{"title":"A Phase 2 study of CPX-351 in combination with venetoclax in patients with newly diagnosed high-risk acute myeloid leukemia","authors":"Wei-Ying Jen, Jennifer Croden, Emmanuel Almanza-Huante, Courtney DiNardo, Kelly Chien, Danielle Hammond, Wei Qiao, Yesid Alvarado, Lucia Masarova, Andres E. Quesada, Sherry Pierce, Alex Bataller, Guillermo Garcia-Manero, Amin Alousi, Nicholas Short, Naval Daver, Farhad Ravandi, Hagop Kantarjian, Tapan M. Kadia","doi":"10.1002/hem3.70214","DOIUrl":"10.1002/hem3.70214","url":null,"abstract":"<p>Venetoclax has been combined with intensive chemotherapy regimens in the treatment of acute myeloid leukemia (AML). We aimed to investigate the safety and efficacy of venetoclax combined with full-dose CPX-351 (CPX + VEN) in newly diagnosed (ND) AML. Seventeen patients with a median age of 59 years (range, 43–69) were treated; 71% had secondary AML, 47% had prior hypomethylating agent (HMA) exposure, 59% had myelodysplastic syndrome (MDS)-related (MR) mutations, 47% had complex karyotype, and 29% were <i>TP53</i> mutated. The overall response rate (ORR) was 82% (95% CI, 57–96) with a composite complete remission rate (CRc) of 71% (95% CI, 50–93). Patients with MR mutations had an ORR of 100% (95% CI, 69–100), including a CRc of 90% (95% CI, 55–100). Patients with prior HMA exposure had a CRc of 63% (95% CI, 24–91). With a median follow-up time of 11.8 months, the median overall survival (OS) was 12.8 months (95% CI, 5–NE) with a 2-year OS of 34% (95% CI, 10–61). Patients with MR mutations had a median OS of 17.9 months versus 5.1 months in patients without MR mutations (P = 0.039). Twelve (86%) of 14 responding patients proceeded to stem cell transplant (SCT); the median recurrence-free survival and OS landmarked from date of SCT were 14.7 months (95% CI, 1–32) and 14.7 months (95% CI, 4–25), respectively. The 4-week mortality was 0% and the 8-week mortality was 17%. The most common adverse events were related to myelosuppression. CPX + VEN resulted in high remission rates and enabled progression to allogenic SCT for the majority of a highly adverse group of ND AML patients.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 10","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12542300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marco Picardi, Annamaria Vincenzi, Novella Pugliese, Claudia Giordano, Maria Prastaro, Roberta Esposito, Fabrizio Pane
<p>Although anthracycline-based chemotherapy provides the best outcomes for Hodgkin lymphoma (HL) patients,<span><sup>1</sup></span> reducing the use of doxorubicin hydrochloride is desirable to lower the risk of anthracycline-induced cardiac dysfunction, especially in the elderly.<span><sup>2-4</sup></span> The most common clinical manifestation of cardiotoxicity is a dose-dependent cardiomyopathy (CMP) leading to chronic heart failure (HF). According to recent reports,<span><sup>2-4</sup></span> the cut-off to prevent cardiotoxicity is 210 mg/m<sup>2</sup>. Data from oncology literature indicate that about 5% of patients receiving >210 mg/m<sup>2</sup> of cumulative anthracycline will develop overt HF 10–20 years after treatment, increasing to 10% when mediastinal radiotherapy is added.<span><sup>2-4</sup></span> However, this incidence is likely underestimated, since over half of elderly patients show some degree of cardiac dysfunction.<span><sup>2-4</sup></span> The 2022 Task Force for Cancer Treatments and Cardiovascular Toxicity of the European Society of Cardiology (ESC) Guidelines<span><sup>4</sup></span> strongly recommend systematic echocardiographic monitoring, including strain rate imaging with measures of global radial and circumferential strain (global longitudinal strain [GLS]) in addition to left ventricular ejection fraction (LVEF) for exploring subclinical signs of impaired ventricular function. The authors advocate diagnosis of anthracycline-induced CMP in the asymptomatic phase, that is, at the onset when GLS declines ≥15% from baseline and/or LVEF falls ≥10% to 40%–49%, allowing early modern HF treatment.<span><sup>2-4</sup></span></p><p>We read with interest the multicenter phase II study by Bröckelmann et al. reporting the outcomes of 49 elderly (median age: 66 years) classic-HL patients with advanced-stage treated frontline between 2015 and 2017, with six cycles of B-CAP, consisting of Brentuximab Vedotin (1.8 mg/kg i.v. Day 1), cyclophosphamide (750 mg/m<sup>2</sup> i.v. d1), doxorubicin (50 mg/m<sup>2</sup> i.v. d1), and prednisone (100 mg po Days 2–6) at 3-weekly intervals.<span><sup>5</sup></span> The maximum dose level of antineoplastic drugs was maintained in 86% of patients, and the mean relative dose intensity, defined as the relative dose over relative duration, was 93%. Ten patients (20%) received consolidative 30-Gy radiotherapy to residual nodal masses (RNMs) with 2-deoxy-2[F-18] fluoro-<span>D</span>-glucose (FDG) uptake in positron emission tomography/computed tomography (PET/CT) scans after completion of B-CAP treatment. At 3 years, progression-free survival (PFS) and overall survival (OS) were 64% and 91%, respectively, with a median follow-up of 35 months. Any grade heart toxicity (according to the National Cancer Institute Common Terminology Criteria for Adverse Events) was reported in 10% of patients (<i>N</i> = 5), with grade 1–2 in 6% (<i>N</i> = 3) and grade 3 in 4% (<i>N</i> = 2). The authors conc
{"title":"Liposomal doxorubicin in place of doxorubicin hydrochloride to prevent anthracycline-induced cardiomyopathy in elderly patients with Hodgkin lymphoma","authors":"Marco Picardi, Annamaria Vincenzi, Novella Pugliese, Claudia Giordano, Maria Prastaro, Roberta Esposito, Fabrizio Pane","doi":"10.1002/hem3.70240","DOIUrl":"https://doi.org/10.1002/hem3.70240","url":null,"abstract":"<p>Although anthracycline-based chemotherapy provides the best outcomes for Hodgkin lymphoma (HL) patients,<span><sup>1</sup></span> reducing the use of doxorubicin hydrochloride is desirable to lower the risk of anthracycline-induced cardiac dysfunction, especially in the elderly.<span><sup>2-4</sup></span> The most common clinical manifestation of cardiotoxicity is a dose-dependent cardiomyopathy (CMP) leading to chronic heart failure (HF). According to recent reports,<span><sup>2-4</sup></span> the cut-off to prevent cardiotoxicity is 210 mg/m<sup>2</sup>. Data from oncology literature indicate that about 5% of patients receiving >210 mg/m<sup>2</sup> of cumulative anthracycline will develop overt HF 10–20 years after treatment, increasing to 10% when mediastinal radiotherapy is added.<span><sup>2-4</sup></span> However, this incidence is likely underestimated, since over half of elderly patients show some degree of cardiac dysfunction.<span><sup>2-4</sup></span> The 2022 Task Force for Cancer Treatments and Cardiovascular Toxicity of the European Society of Cardiology (ESC) Guidelines<span><sup>4</sup></span> strongly recommend systematic echocardiographic monitoring, including strain rate imaging with measures of global radial and circumferential strain (global longitudinal strain [GLS]) in addition to left ventricular ejection fraction (LVEF) for exploring subclinical signs of impaired ventricular function. The authors advocate diagnosis of anthracycline-induced CMP in the asymptomatic phase, that is, at the onset when GLS declines ≥15% from baseline and/or LVEF falls ≥10% to 40%–49%, allowing early modern HF treatment.<span><sup>2-4</sup></span></p><p>We read with interest the multicenter phase II study by Bröckelmann et al. reporting the outcomes of 49 elderly (median age: 66 years) classic-HL patients with advanced-stage treated frontline between 2015 and 2017, with six cycles of B-CAP, consisting of Brentuximab Vedotin (1.8 mg/kg i.v. Day 1), cyclophosphamide (750 mg/m<sup>2</sup> i.v. d1), doxorubicin (50 mg/m<sup>2</sup> i.v. d1), and prednisone (100 mg po Days 2–6) at 3-weekly intervals.<span><sup>5</sup></span> The maximum dose level of antineoplastic drugs was maintained in 86% of patients, and the mean relative dose intensity, defined as the relative dose over relative duration, was 93%. Ten patients (20%) received consolidative 30-Gy radiotherapy to residual nodal masses (RNMs) with 2-deoxy-2[F-18] fluoro-<span>D</span>-glucose (FDG) uptake in positron emission tomography/computed tomography (PET/CT) scans after completion of B-CAP treatment. At 3 years, progression-free survival (PFS) and overall survival (OS) were 64% and 91%, respectively, with a median follow-up of 35 months. Any grade heart toxicity (according to the National Cancer Institute Common Terminology Criteria for Adverse Events) was reported in 10% of patients (<i>N</i> = 5), with grade 1–2 in 6% (<i>N</i> = 3) and grade 3 in 4% (<i>N</i> = 2). The authors conc","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 10","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145317218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hanna Kirchhoff, Caroline Schoenherr, Lisa Fleischer, Elizabeth K. Schweighart, Ruth Esser, Steven R. Talbot, Axel Schambach, Ulrike Koehl, Olaf Heidenreich, Matthias Eder, Michaela Scherr
Anti-CD19 CAR NK cells may provide a promising non-HLA-restricted immune cell product and have been clinically studied primarily on low-grade B-cell lymphoma patients. We used retroviral gene transfer to generate aCD19 CAR NK cells from the peripheral blood of healthy volunteers. We evaluated their efficacy in B-lineage acute lymphoblastic leukemia (BCP-ALL) using patient-derived xenograft (PDX) cells in vitro and in vivo. aCD19 CAR NK cells showed potent specific cytotoxicity against eleven BCP-ALL PDX models in vitro. When used as monotherapy in vivo, they provided a survival benefit, albeit complete remissions were not achieved. Due to the low accumulation of aCD19 CAR NK cells in the bone marrow, we used targeted pharmacotherapy based on venetoclax, dexamethasone, and dasatinib to induce remission in BCR-ABL-positive ALL and combined it with aCD19 NK cell therapy for consolidation. Overlapping therapy enhanced aCD19 CAR NK cell cytotoxicity in vitro and significantly prolonged survival in two high-risk BCP-ALL PDX models with individual long-term remissions. Relapse cells showed no signs of therapy-induced evolution as CD19 expression, sensitivity to venetoclax, and aCD19 CAR cell cytotoxicity remained unchanged. These data demonstrate the potential of aCD19 CAR NK cells as a component of combinatorial therapy for BCP-ALL, which should be further evaluated in clinical trials.
抗cd19 CAR - NK细胞可能是一种很有前途的非hla限制性免疫细胞产物，并已在低级别b细胞淋巴瘤患者中进行了临床研究。我们使用逆转录病毒基因转移从健康志愿者的外周血中产生aCD19 CAR NK细胞。我们在体外和体内使用患者来源的异种移植（PDX）细胞评估了它们对b系急性淋巴细胞白血病（BCP-ALL）的疗效。aCD19 CAR NK细胞在体外对11种BCP-ALL PDX模型显示出强大的特异性细胞毒性。当用作体内单药治疗时，它们提供了生存益处，尽管没有实现完全缓解。由于aCD19 CAR NK细胞在骨髓中的积累较低，我们采用基于venetoclax、地塞米松和达沙替尼的靶向药物治疗诱导bcr - abl阳性ALL缓解，并联合aCD19 NK细胞治疗巩固。重叠治疗增强了体外aCD19 CAR NK细胞的细胞毒性，显著延长了两种高风险BCP-ALL PDX模型的生存期，个体长期缓解。复发细胞没有表现出治疗诱导的进化迹象，因为CD19表达、对venetoclax的敏感性和aCD19 CAR细胞毒性保持不变。这些数据表明aCD19 CAR - NK细胞作为BCP-ALL联合治疗的一个组成部分的潜力，应该在临床试验中进一步评估。
{"title":"Combination of targeted pharmacotherapy and immunotherapy with anti-CD19 CAR NK cells in acute lymphoblastic leukemia","authors":"Hanna Kirchhoff, Caroline Schoenherr, Lisa Fleischer, Elizabeth K. Schweighart, Ruth Esser, Steven R. Talbot, Axel Schambach, Ulrike Koehl, Olaf Heidenreich, Matthias Eder, Michaela Scherr","doi":"10.1002/hem3.70238","DOIUrl":"10.1002/hem3.70238","url":null,"abstract":"<p>Anti-CD19 CAR NK cells may provide a promising non-HLA-restricted immune cell product and have been clinically studied primarily on low-grade B-cell lymphoma patients. We used retroviral gene transfer to generate aCD19 CAR NK cells from the peripheral blood of healthy volunteers. We evaluated their efficacy in B-lineage acute lymphoblastic leukemia (BCP-ALL) using patient-derived xenograft (PDX) cells in vitro and in vivo. aCD19 CAR NK cells showed potent specific cytotoxicity against eleven BCP-ALL PDX models in vitro. When used as monotherapy in vivo, they provided a survival benefit, albeit complete remissions were not achieved. Due to the low accumulation of aCD19 CAR NK cells in the bone marrow, we used targeted pharmacotherapy based on venetoclax, dexamethasone, and dasatinib to induce remission in BCR-ABL-positive ALL and combined it with aCD19 NK cell therapy for consolidation. Overlapping therapy enhanced aCD19 CAR NK cell cytotoxicity in vitro and significantly prolonged survival in two high-risk BCP-ALL PDX models with individual long-term remissions. Relapse cells showed no signs of therapy-induced evolution as CD19 expression, sensitivity to venetoclax, and aCD19 CAR cell cytotoxicity remained unchanged. These data demonstrate the potential of aCD19 CAR NK cells as a component of combinatorial therapy for BCP-ALL, which should be further evaluated in clinical trials.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 10","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12527222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tarec Christoffer El-Galaly, Ananda Plate, Gita Thanarajasingam, Robin Doeswijk, Martin Dreyling, Paul J. Bröckelmann
<p>The treatment landscape of hematologic malignancies is changing with a shift away from chemo- and radiotherapy towards targeted approaches and immunotherapies.<span><sup>1</sup></span> These novel treatment strategies often result in longer survival and, in some cases, have turned cancers with historically dismal outcomes into chronic or even curable disease.<span><sup>2, 3</sup></span> However, comprehensive characterization of distinct side effect profiles in clinically meaningful ways remains a major challenge. There are many relevant stakeholders with an interest in safety reporting, and diverging perceptions of importance can create tensions between patients, clinicians, investigators, commercial sponsors, and regulatory authorities.<span><sup>4</sup></span> Clinical research, including interventional clinical trials (CTs), is a key factor in ensuring patient safety through establishing evidence-based treatments that truly benefit patients. The European Hematology Association (EHA) has championed several activities to promote better safety reporting with less administrative burden in CTs. Herein, we summarize current initiatives and perspectives to modernize the assessment and reporting of treatment tolerability in hematologic malignancies.</p><p>Since its foundation and first position paper in 2018,<span><sup>5</sup></span> The Lancet Haematology (TLH) Commission on Adverse Event (AE) Reporting has advocated for improving how tolerability of treatment is measured and reported. This international, multistakeholder consortium asserts that evaluation of treatment-related toxicity should go beyond reporting of maximum grade toxicities, currently the standard approach by which key safety data are presented in scientific communications. The Commission includes patient advocates, clinicians, clinical investigators, biostatistician, pharmacists, and multiple regulatory agency representatives. The first position papers were presented in an event at the EHA annual congress in 2018 with a follow-up to monitor progress in 2022. In the 2025 update,<span><sup>6</sup></span> the authors provided an actionable framework to substantially improve and harmonize how toxicities are collected, analyzed, and reported. Specifically, they advocate for a more comprehensive depiction of longitudinal toxicity trajectories, improved visualization, implementation of interactive dashboards to explore tolerability data, and increasing use of patient-reported outcomes (PROs),<span><sup>7, 8</sup></span> including in early-phase trials and throughout the regulatory process. Drawing on our growing knowledge of the toxicity patterns associated with novel therapies, the authors additionally propose a practical framework to enhance the evaluation, reporting, and interpretation of treatment tolerability in the context of targeted and immunotherapies.<span><sup>9</sup></span> Thereby, the TLH AE Commission aims to put patients first and outlines pragmatic steps to revise our a
{"title":"Patient-centered and proportionate safety reporting in clinical trials facilitates evidence-based medicine for the benefit of patients and society: An EHA priority","authors":"Tarec Christoffer El-Galaly, Ananda Plate, Gita Thanarajasingam, Robin Doeswijk, Martin Dreyling, Paul J. Bröckelmann","doi":"10.1002/hem3.70239","DOIUrl":"10.1002/hem3.70239","url":null,"abstract":"<p>The treatment landscape of hematologic malignancies is changing with a shift away from chemo- and radiotherapy towards targeted approaches and immunotherapies.<span><sup>1</sup></span> These novel treatment strategies often result in longer survival and, in some cases, have turned cancers with historically dismal outcomes into chronic or even curable disease.<span><sup>2, 3</sup></span> However, comprehensive characterization of distinct side effect profiles in clinically meaningful ways remains a major challenge. There are many relevant stakeholders with an interest in safety reporting, and diverging perceptions of importance can create tensions between patients, clinicians, investigators, commercial sponsors, and regulatory authorities.<span><sup>4</sup></span> Clinical research, including interventional clinical trials (CTs), is a key factor in ensuring patient safety through establishing evidence-based treatments that truly benefit patients. The European Hematology Association (EHA) has championed several activities to promote better safety reporting with less administrative burden in CTs. Herein, we summarize current initiatives and perspectives to modernize the assessment and reporting of treatment tolerability in hematologic malignancies.</p><p>Since its foundation and first position paper in 2018,<span><sup>5</sup></span> The Lancet Haematology (TLH) Commission on Adverse Event (AE) Reporting has advocated for improving how tolerability of treatment is measured and reported. This international, multistakeholder consortium asserts that evaluation of treatment-related toxicity should go beyond reporting of maximum grade toxicities, currently the standard approach by which key safety data are presented in scientific communications. The Commission includes patient advocates, clinicians, clinical investigators, biostatistician, pharmacists, and multiple regulatory agency representatives. The first position papers were presented in an event at the EHA annual congress in 2018 with a follow-up to monitor progress in 2022. In the 2025 update,<span><sup>6</sup></span> the authors provided an actionable framework to substantially improve and harmonize how toxicities are collected, analyzed, and reported. Specifically, they advocate for a more comprehensive depiction of longitudinal toxicity trajectories, improved visualization, implementation of interactive dashboards to explore tolerability data, and increasing use of patient-reported outcomes (PROs),<span><sup>7, 8</sup></span> including in early-phase trials and throughout the regulatory process. Drawing on our growing knowledge of the toxicity patterns associated with novel therapies, the authors additionally propose a practical framework to enhance the evaluation, reporting, and interpretation of treatment tolerability in the context of targeted and immunotherapies.<span><sup>9</sup></span> Thereby, the TLH AE Commission aims to put patients first and outlines pragmatic steps to revise our a","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 10","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12526710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Central nervous system multiple myeloma (CNS-MM) is a rare and aggressive extramedullary manifestation of multiple myeloma, associated with poor prognosis and significant treatment challenges. Due to its rarity, data on incidence, risk factors, optimal therapeutic approaches, and long-term outcomes remain limited. This review aims to elucidate the current diagnostic and therapeutic challenges of CNS-MM and provide practical insights into real-life management strategies.
{"title":"Central nervous system myeloma: Pathogenesis, diagnostic challenges, and practical management strategies","authors":"Eirini Katodritou, Evangelos Terpos","doi":"10.1002/hem3.70213","DOIUrl":"10.1002/hem3.70213","url":null,"abstract":"<p>Central nervous system multiple myeloma (CNS-MM) is a rare and aggressive extramedullary manifestation of multiple myeloma, associated with poor prognosis and significant treatment challenges. Due to its rarity, data on incidence, risk factors, optimal therapeutic approaches, and long-term outcomes remain limited. This review aims to elucidate the current diagnostic and therapeutic challenges of CNS-MM and provide practical insights into real-life management strategies.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 10","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12516910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karl Haller, Asita Behzadi, Johannes C. Ehrenthal, Lars Bullinger, Johann Ahn
<p>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option for various hematological malignancies and autoimmune diseases, and typically requires a 4–6-week hospital stay in protective isolation.<span><sup>1</sup></span> Patients frequently endure intense physical and psychological distress, with up to a third developing clinically significant anxiety or depression.<span><sup>2</sup></span> Isolation limits contact with family and peers, exacerbating distress and thus poses a particular challenge.<span><sup>3</sup></span> Despite this, few supportive interventions target allo-HSCT patients during hospitalization, and none focus on group therapy in this phase.<span><sup>4</sup></span> Yet group programs can benefit cancer patients by fostering peer support, coping strategy exchange, and emotional self-efficacy.<span><sup>5, 6</sup></span></p><p>Challenges such as immunosuppression, unpredictable treatment schedules, high symptom burden, and potential emotional strain when sharing concerns with others complicate group interventions. A recent prehabilitation group program for allo-HSCT patients reported similar obstacles, including time constraints, other medical priorities, and low initial distress to motivate participation.<span><sup>7</sup></span> Given these complexities, feasibility studies are necessary before larger trials. This study developed and tested a novel online group intervention tailored to allo-HSCT inpatients.</p><p>Following CONSORT guidelines for pilot and feasibility trials, a quasi-experimental matched-control study was conducted to assess the feasibility, acceptability, and exploratory outcomes. Feasibility was assessed via recruitment and retention rates, while acceptability was evaluated using self-report satisfaction measures. Potential adverse effects and deviations from the intervention manual were monitored. A randomized controlled design was deemed inappropriate due to the early stage of intervention development and high disease burden, instead, a matched-control design allowed all interested patients to participate while providing comparative data. The target sample size was 18 per group, considered realistic for the 6-month study period. Eligibility criteria included age > 18, current inpatient allo-HSCT, and sufficient German language proficiency. Assessments occurred at admission and discharge.</p><p>The intervention was developed and manualized based on literature, patient interviews, and expert input, including hematologists, nurses, psycho-oncologists, and patient representatives.<span><sup>8</sup></span> Patients expressed interest in peer exchange, flexible participation, and psycho-oncological guidance. The final format consisted of weekly 60-min sessions via a privacy-compliant video platform, featuring tailored group rules, an opening round, thematic discussions (topics: 1. Coping with Isolation and Daily Routines, 2. Communication and social support, 3. Coping with ill
{"title":"Feasibility and acceptability of an online psychological group intervention for allogeneic hematopoietic stem cell transplantation inpatients","authors":"Karl Haller, Asita Behzadi, Johannes C. Ehrenthal, Lars Bullinger, Johann Ahn","doi":"10.1002/hem3.70237","DOIUrl":"10.1002/hem3.70237","url":null,"abstract":"<p>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option for various hematological malignancies and autoimmune diseases, and typically requires a 4–6-week hospital stay in protective isolation.<span><sup>1</sup></span> Patients frequently endure intense physical and psychological distress, with up to a third developing clinically significant anxiety or depression.<span><sup>2</sup></span> Isolation limits contact with family and peers, exacerbating distress and thus poses a particular challenge.<span><sup>3</sup></span> Despite this, few supportive interventions target allo-HSCT patients during hospitalization, and none focus on group therapy in this phase.<span><sup>4</sup></span> Yet group programs can benefit cancer patients by fostering peer support, coping strategy exchange, and emotional self-efficacy.<span><sup>5, 6</sup></span></p><p>Challenges such as immunosuppression, unpredictable treatment schedules, high symptom burden, and potential emotional strain when sharing concerns with others complicate group interventions. A recent prehabilitation group program for allo-HSCT patients reported similar obstacles, including time constraints, other medical priorities, and low initial distress to motivate participation.<span><sup>7</sup></span> Given these complexities, feasibility studies are necessary before larger trials. This study developed and tested a novel online group intervention tailored to allo-HSCT inpatients.</p><p>Following CONSORT guidelines for pilot and feasibility trials, a quasi-experimental matched-control study was conducted to assess the feasibility, acceptability, and exploratory outcomes. Feasibility was assessed via recruitment and retention rates, while acceptability was evaluated using self-report satisfaction measures. Potential adverse effects and deviations from the intervention manual were monitored. A randomized controlled design was deemed inappropriate due to the early stage of intervention development and high disease burden, instead, a matched-control design allowed all interested patients to participate while providing comparative data. The target sample size was 18 per group, considered realistic for the 6-month study period. Eligibility criteria included age > 18, current inpatient allo-HSCT, and sufficient German language proficiency. Assessments occurred at admission and discharge.</p><p>The intervention was developed and manualized based on literature, patient interviews, and expert input, including hematologists, nurses, psycho-oncologists, and patient representatives.<span><sup>8</sup></span> Patients expressed interest in peer exchange, flexible participation, and psycho-oncological guidance. The final format consisted of weekly 60-min sessions via a privacy-compliant video platform, featuring tailored group rules, an opening round, thematic discussions (topics: 1. Coping with Isolation and Daily Routines, 2. Communication and social support, 3. Coping with ill","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 10","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12516907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Niccolò Bolli, Mattia D'Agostino, Tina Bagratuni, Mario Boccadoro, Michele Cavo, Christoph Driessen, Hermann Einsele, Monika Engelhardt, Francesca Gay, Norma C. Gutiérrez, Roman Hájek, Toril Holien, Cristina João, Martin Kaiser, K. Martin Kortüm, Lisa Leypoldt, Philippe Moreau, Pellegrino Musto, Enrique M. Ocio, Marc S. Raab, Leo Rasche, Fredrik Schjesvold, Tereza Sevcikova, Evangelos Terpos, Cyrille Touzeau, Niels W. C. J. Van de Donk, Mark van Duin, Katja Weisel, Elena Zamagni, Tom Cupedo, Pieter Sonneveld, Carolina Terragna
Given the evolving understanding of genetic risk factors in multiple myeloma (MM), this paper assesses whether next-generation sequencing (NGS) could complement or even replace fluorescence in situ hybridization (FISH) at diagnosis. A structured consensus process within European Myeloma Network (EMN) clinical and laboratory groups was conducted to establish recommendations on routine clinical deployment of NGS in MM risk assessment. Four key questions were addressed: (1) should NGS be used in addition to, or alternatively to FISH in identifying prognostic genetic markers, (2) which prognostic markers are most relevant for analysis by NGS, (3) which patients should be offered NGS testing, and (4) what is the optimal timing for performing NGS. The panel reviewed current literature, evaluated available NGS technologies, and compared their performance with that of FISH-based methodologies. The paper reviews current standard NGS protocols, quality control measures, and provides practical points for the implementation of an NGS diagnosis in MM. While NGS shows promise in improving risk stratification, challenges such as cost, accessibility, and clinical workflow integration must be addressed. The consensus supports the initial incorporation of NGS as a complementary tool to FISH. Recommendations emphasize that: a broader list of genetic events should be incorporated into such a test than what currently requested by risk scores; the test should be offered at least to the fit patients who could be candidates for modern triplet or quadruplet treatments; the test should be repeated at the time relapse, especially in the future when targeted treatments may mandate the use of predictive markers of response. This consensus provides a foundation for future research and policy development, guiding the adoption of NGS in MM risk assessment.
{"title":"European Myeloma Network Group Consensus Statement on the use of next-generation sequencing for prognostic stratification of newly diagnosed multiple myeloma","authors":"Niccolò Bolli, Mattia D'Agostino, Tina Bagratuni, Mario Boccadoro, Michele Cavo, Christoph Driessen, Hermann Einsele, Monika Engelhardt, Francesca Gay, Norma C. Gutiérrez, Roman Hájek, Toril Holien, Cristina João, Martin Kaiser, K. Martin Kortüm, Lisa Leypoldt, Philippe Moreau, Pellegrino Musto, Enrique M. Ocio, Marc S. Raab, Leo Rasche, Fredrik Schjesvold, Tereza Sevcikova, Evangelos Terpos, Cyrille Touzeau, Niels W. C. J. Van de Donk, Mark van Duin, Katja Weisel, Elena Zamagni, Tom Cupedo, Pieter Sonneveld, Carolina Terragna","doi":"10.1002/hem3.70216","DOIUrl":"10.1002/hem3.70216","url":null,"abstract":"<p>Given the evolving understanding of genetic risk factors in multiple myeloma (MM), this paper assesses whether next-generation sequencing (NGS) could complement or even replace fluorescence in situ hybridization (FISH) at diagnosis. A structured consensus process within European Myeloma Network (EMN) clinical and laboratory groups was conducted to establish recommendations on routine clinical deployment of NGS in MM risk assessment. Four key questions were addressed: (1) should NGS be used in addition to, or alternatively to FISH in identifying prognostic genetic markers, (2) which prognostic markers are most relevant for analysis by NGS, (3) which patients should be offered NGS testing, and (4) what is the optimal timing for performing NGS. The panel reviewed current literature, evaluated available NGS technologies, and compared their performance with that of FISH-based methodologies. The paper reviews current standard NGS protocols, quality control measures, and provides practical points for the implementation of an NGS diagnosis in MM. While NGS shows promise in improving risk stratification, challenges such as cost, accessibility, and clinical workflow integration must be addressed. The consensus supports the initial incorporation of NGS as a complementary tool to FISH. Recommendations emphasize that: a broader list of genetic events should be incorporated into such a test than what currently requested by risk scores; the test should be offered at least to the fit patients who could be candidates for modern triplet or quadruplet treatments; the test should be repeated at the time relapse, especially in the future when targeted treatments may mandate the use of predictive markers of response. This consensus provides a foundation for future research and policy development, guiding the adoption of NGS in MM risk assessment.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 10","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12517052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Koschmieder S. Novel approaches in myelofibrosis. HemaSphere. 2024;8(12):e70056. doi:10.1002/hem3.70056
A funder was not acknowledged in the original article. The following statement has now been added in the Funding section: “Open Access funding enabled and organized by Projekt DEAL.”
The original article has been updated. We apologize for this error.
[这更正了文章DOI: 10.1002/hem3.70056.]。
{"title":"Correction to “Novel approaches in myelofibrosis”","authors":"","doi":"10.1002/hem3.70222","DOIUrl":"10.1002/hem3.70222","url":null,"abstract":"<p>Koschmieder S. Novel approaches in myelofibrosis. <i>HemaSphere</i>. 2024;8(12):e70056. doi:10.1002/hem3.70056</p><p>A funder was not acknowledged in the original article. The following statement has now been added in the Funding section: “Open Access funding enabled and organized by Projekt DEAL.”</p><p>The original article has been updated. We apologize for this error.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 10","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12516912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adrian Mosquera Orgueira, Marta Sonia Gonzalez Perez, Mattia D'Agostino, David A. Cairns, Alessandra Larocca, Juan José Lahuerta Palacios, Ruth Wester, Uta Bertsch, Anders Waage, Elena Zamagni, Carlos Pérez Míguez, Javier Alberto Rojas Martínez, Elias K. Mai, Davide Crucitti, Hans Salwender, Daniele Dall'Olio, Gastone Castellani, Manuel Piñeiro Fiel, Sara Bringhen, Sonja Zweegman, Michele Cavo, Sofía Iqbal, Jesus Maria Hernandez Rivas, Benedetto Bruno, Gordon Cook, Martin F. Kaiser, Hartmut Goldschmidt, Niels W. C. J. Van De Donk, Graham Jackson, Jesús F. San-Miguel, Mario Boccadoro, Maria-Victoria Mateos, Pieter Sonneveld
Traditional risk stratification in multiple myeloma (MM) relies on clinical and cytogenetic parameters but has limited predictive accuracy. Machine learning (ML) offers a novel approach by leveraging large datasets and complex variable interactions. This study aimed to develop and validate novel ML-driven prognostic scores for newly diagnosed MM (NDMM), with the goal of improving upon existing ones. To this end, we analyzed data from the EMN–HARMONY MM cohort, comprising 14,345 patients, including 10,843 NDMM patients enrolled across 16 clinical trials. Three ML models were developed: (1) a comprehensive model incorporating 20 variables, (2) a reduced model including six key variables (age, hemoglobin, β2-microglobulin, albumin, 1q gain, and 17p deletion), and (3) a cytogenetics-free model. All models were internally validated using out-of-bag cross-validation and externally validated with data from the Myeloma XI trial. Model performance was evaluated using the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (ROC-AUC). The comprehensive model achieved C-index values of 0.666 (training) and 0.667 (test) for overall survival (OS) and 0.620/0.627 for progression-free survival (PFS). The reduced model maintained accuracy (OS: 0.658/0.657; PFS: 0.608/0.614). The cytogenetics-free model showed C-index values of 0.636/0.643 for OS and 0.600/0.610 for PFS. Incorporating treatment type and best response to first-line treatment further improved performance. The new prognostic models improved over the International Staging System (ISS), Revised International Staging System (R-ISS), and Second Revision of the International Staging System (R2-ISS) and were reproducible in real-world and relapsed/refractory MM, including daratumumab-treated patients. This ML-based risk stratification strategy provides individualized risk predictions, surpassing traditional group-based methods and demonstrating broad applicability across patient subgroups. An online calculator is available at https://taxonomy.harmony-platform.eu/riskcalculator/.
{"title":"Machine learning risk stratification strategy for multiple myeloma: Insights from the EMN–HARMONY Alliance platform","authors":"Adrian Mosquera Orgueira, Marta Sonia Gonzalez Perez, Mattia D'Agostino, David A. Cairns, Alessandra Larocca, Juan José Lahuerta Palacios, Ruth Wester, Uta Bertsch, Anders Waage, Elena Zamagni, Carlos Pérez Míguez, Javier Alberto Rojas Martínez, Elias K. Mai, Davide Crucitti, Hans Salwender, Daniele Dall'Olio, Gastone Castellani, Manuel Piñeiro Fiel, Sara Bringhen, Sonja Zweegman, Michele Cavo, Sofía Iqbal, Jesus Maria Hernandez Rivas, Benedetto Bruno, Gordon Cook, Martin F. Kaiser, Hartmut Goldschmidt, Niels W. C. J. Van De Donk, Graham Jackson, Jesús F. San-Miguel, Mario Boccadoro, Maria-Victoria Mateos, Pieter Sonneveld","doi":"10.1002/hem3.70228","DOIUrl":"https://doi.org/10.1002/hem3.70228","url":null,"abstract":"<p>Traditional risk stratification in multiple myeloma (MM) relies on clinical and cytogenetic parameters but has limited predictive accuracy. Machine learning (ML) offers a novel approach by leveraging large datasets and complex variable interactions. This study aimed to develop and validate novel ML-driven prognostic scores for newly diagnosed MM (NDMM), with the goal of improving upon existing ones. To this end, we analyzed data from the EMN–HARMONY MM cohort, comprising 14,345 patients, including 10,843 NDMM patients enrolled across 16 clinical trials. Three ML models were developed: (1) a comprehensive model incorporating 20 variables, (2) a reduced model including six key variables (age, hemoglobin, β2-microglobulin, albumin, 1q gain, and 17p deletion), and (3) a cytogenetics-free model. All models were internally validated using out-of-bag cross-validation and externally validated with data from the Myeloma XI trial. Model performance was evaluated using the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (ROC-AUC). The comprehensive model achieved C-index values of 0.666 (training) and 0.667 (test) for overall survival (OS) and 0.620/0.627 for progression-free survival (PFS). The reduced model maintained accuracy (OS: 0.658/0.657; PFS: 0.608/0.614). The cytogenetics-free model showed C-index values of 0.636/0.643 for OS and 0.600/0.610 for PFS. Incorporating treatment type and best response to first-line treatment further improved performance. The new prognostic models improved over the International Staging System (ISS), Revised International Staging System (R-ISS), and Second Revision of the International Staging System (R2-ISS) and were reproducible in real-world and relapsed/refractory MM, including daratumumab-treated patients. This ML-based risk stratification strategy provides individualized risk predictions, surpassing traditional group-based methods and demonstrating broad applicability across patient subgroups. An online calculator is available at https://taxonomy.harmony-platform.eu/riskcalculator/.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 10","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70228","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145272232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kazianka L, Pichler A, Agreiter C, et al. Comparing functional and genomic-based precision medicine in blood cancer patients. HemaSphere. 2025;9(4):e70129. doi:10.1002/hem3.70129
A funder was not acknowledged in the original article. The following statement has now been added in the Funding section: “Open Access funding provided by Medizinische Universitat Wien/KEMÖ.”
The original article has been updated. We apologize for this error.
[这更正了文章DOI: 10.1002/hem3.70129]。
{"title":"Correction to “Comparing functional and genomic-based precision medicine in blood cancer patients”","authors":"","doi":"10.1002/hem3.70220","DOIUrl":"10.1002/hem3.70220","url":null,"abstract":"<p>Kazianka L, Pichler A, Agreiter C, et al. Comparing functional and genomic-based precision medicine in blood cancer patients. <i>HemaSphere</i>. 2025;9(4):e70129. doi:10.1002/hem3.70129</p><p>A funder was not acknowledged in the original article. The following statement has now been added in the Funding section: “Open Access funding provided by Medizinische Universitat Wien/KEMÖ.”</p><p>The original article has been updated. We apologize for this error.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 10","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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