Pub Date : 2024-05-21DOI: 10.1016/j.bneo.2024.100018
Ulrich Dührsen , Andreas Bockisch , Bernd Hertenstein , Imke E. Karsten , Frank Kroschinsky , Michael Heuser , Andreas Hochhaus , Heinz-Gert Höffkes , Dirk Behringer , Gabriele Prange-Krex , Mareike Tometten , Martin Grieshammer , Götz U. Grigoleit , Oliver Schmalz , Karin Jordan , Helga Bernhard , Tobias Gaska , Aristoteles Giagounidis , Roland Schroers , Uwe M. Martens , M. Neuhäuser
Abstract
The PETAL (Positron Emission Tomography–Guided Therapy of Aggressive Non-Hodgkin Lymphomas) trial investigated whether treatment intensification after 2 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; plus rituximab [R] for CD20+ lymphomas) improved survival in aggressive non-Hodgkin lymphoma. A total of 754 patients (87.5%) had a negative and 108 (12.5%) had a positive interim positron emission tomography (iPET) scan. iPET-positive patients were randomly assigned to receive another 6 (R-)CHOP cycles or 6 blocks of a more intensive protocol. Interim PET-negative patients received another 4 cycles of R-CHOP with or without 2 additional doses of R. After a median follow-up of 4 years, treatment intensification had not improved outcome. These results were confirmed after 10.3 years of follow-up. The present analysis also describes the management of relapse that was part of the study. Among 240 relapsing patients, 94 of 133 autologous transplantation–eligible patients (70.7%) and 16 of 107 ineligible patients (15.0%) received the salvage treatments recommended in the study protocol. Adherence to recommendations had no impact on outcome. Best results were seen after allogeneic transplantation, followed by autologous transplantation and treatment without transplantation (5-year overall survival rate, 64.3% vs 45.5% vs 22.6%), but patients undergoing allogeneic transplantation were significantly younger and their disease was well controlled at the time of transplantation. Early outcome prediction by iPET, alone or in combination with other methods, is a powerful tool to investigate the value of immunological treatment options for patients with a poor response to chemotherapy. This trial was registered at ClinicalTrials.gov as #NCT00554164.
摘要PETAL（正电子发射断层扫描引导的侵袭性非霍奇金淋巴瘤治疗）试验研究了在环磷酰胺、多柔比星、长春新碱和泼尼松（CHOP；CD20+淋巴瘤加利妥昔单抗[R]）治疗2个周期后加强治疗是否能提高侵袭性非霍奇金淋巴瘤患者的生存率。共有 754 名患者（87.5%）的中期正电子发射断层扫描（iPET）结果为阴性，108 名患者（12.5%）的中期正电子发射断层扫描（iPET）结果为阳性。中位随访 4 年后，强化治疗并未改善疗效。这些结果在随访 10.3 年后得到了证实。本分析报告还介绍了作为研究一部分的复发治疗情况。在240名复发患者中，133名符合自体移植条件的患者中有94名（70.7%）和107名不符合条件的患者中有16名（15.0%）接受了研究方案中建议的挽救治疗。遵守建议对结果没有影响。接受同种异体移植的疗效最好，其次是自体移植和不进行移植的治疗（5年总生存率分别为64.3% vs 45.5% vs 22.6%），但接受同种异体移植的患者明显更年轻，而且移植时病情控制良好。通过iPET单独或结合其他方法进行早期结果预测，是研究化疗反应不佳患者免疫治疗方案价值的有力工具。该试验已在 ClinicalTrials.gov 注册，编号为 #NCT00554164。
{"title":"Response-guided first-line therapy and treatment of relapse in aggressive lymphoma: 10-year follow-up of the PETAL trial","authors":"Ulrich Dührsen , Andreas Bockisch , Bernd Hertenstein , Imke E. Karsten , Frank Kroschinsky , Michael Heuser , Andreas Hochhaus , Heinz-Gert Höffkes , Dirk Behringer , Gabriele Prange-Krex , Mareike Tometten , Martin Grieshammer , Götz U. Grigoleit , Oliver Schmalz , Karin Jordan , Helga Bernhard , Tobias Gaska , Aristoteles Giagounidis , Roland Schroers , Uwe M. Martens , M. Neuhäuser","doi":"10.1016/j.bneo.2024.100018","DOIUrl":"10.1016/j.bneo.2024.100018","url":null,"abstract":"<div><h3>Abstract</h3><p>The PETAL (Positron Emission Tomography–Guided Therapy of Aggressive Non-Hodgkin Lymphomas) trial investigated whether treatment intensification after 2 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; plus rituximab [R] for CD20<sup>+</sup> lymphomas) improved survival in aggressive non-Hodgkin lymphoma. A total of 754 patients (87.5%) had a negative and 108 (12.5%) had a positive interim positron emission tomography (iPET) scan. iPET-positive patients were randomly assigned to receive another 6 (R-)CHOP cycles or 6 blocks of a more intensive protocol. Interim PET-negative patients received another 4 cycles of R-CHOP with or without 2 additional doses of R. After a median follow-up of 4 years, treatment intensification had not improved outcome. These results were confirmed after 10.3 years of follow-up. The present analysis also describes the management of relapse that was part of the study. Among 240 relapsing patients, 94 of 133 autologous transplantation–eligible patients (70.7%) and 16 of 107 ineligible patients (15.0%) received the salvage treatments recommended in the study protocol. Adherence to recommendations had no impact on outcome. Best results were seen after allogeneic transplantation, followed by autologous transplantation and treatment without transplantation (5-year overall survival rate, 64.3% vs 45.5% vs 22.6%), but patients undergoing allogeneic transplantation were significantly younger and their disease was well controlled at the time of transplantation. Early outcome prediction by iPET, alone or in combination with other methods, is a powerful tool to investigate the value of immunological treatment options for patients with a poor response to chemotherapy. This trial was registered at <span>ClinicalTrials.gov</span><svg><path></path></svg> as #NCT00554164.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 3","pages":"Article 100018"},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000189/pdfft?md5=0e7371b07f0b752e8ed5c88b58052061&pid=1-s2.0-S2950328024000189-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141145706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-20DOI: 10.1016/j.bneo.2024.100019
Christopher S. Strouse , Vanessa E. Siebert , Bradley T. Loeffler , Bradley D. McDowell , Brian J. Smith , Brian K. Link
Abstract
Bendamustine is among the most commonly used chemoimmunotherapies for patients with follicular lymphoma (FL). It is typically delivered with a goal regimen consisting of 6 cycles, but it is possible that treatment goals could be achieved with fewer cycles, particularly in older patients. We used data from the National Cancer Institute (NCI) linkage between Surveillance, Epidemiology, and End Results program and Medicare claims to evaluate the overall survival of patients with FL receiving 3 to 4 vs 5 to 6 cycles of bendamustine. Patients receiving 1 to 2 cycles of bendamustine chemotherapy were not included. Patients receiving 5 to 6 cycles of bendamustine were significantly younger (mean age, 75.0 vs 76.2 years; P < .01) and had fewer comorbidities by the NCI comorbidity index (mean score, 1.7 vs 2.0; P = .05) than those receiving 3 to 4 cycles of bendamustine, and on univariate analysis exhibited significantly lower risk of death (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.57-0.98; P = .04). However, multivariate analysis controlling for age and comorbidity did not reveal a significant association between overall survival and number of cycles of bendamustine (HR, 0.87; 95% CI, 0.66-1.15; P = .33). Limitations inherent to use of data such as these for causal inference are acknowledged. Nonetheless, these analyses suggest some older patients with FL achieve satisfactory survival outcomes even with lesser bendamustine exposure, and future efforts to prospectively identify such patients are warranted.
{"title":"Optimal number of cycles of bendamustine as initial chemoimmunotherapy for older patients with follicular lymphoma","authors":"Christopher S. Strouse , Vanessa E. Siebert , Bradley T. Loeffler , Bradley D. McDowell , Brian J. Smith , Brian K. Link","doi":"10.1016/j.bneo.2024.100019","DOIUrl":"10.1016/j.bneo.2024.100019","url":null,"abstract":"<div><h3>Abstract</h3><p>Bendamustine is among the most commonly used chemoimmunotherapies for patients with follicular lymphoma (FL). It is typically delivered with a goal regimen consisting of 6 cycles, but it is possible that treatment goals could be achieved with fewer cycles, particularly in older patients. We used data from the National Cancer Institute (NCI) linkage between Surveillance, Epidemiology, and End Results program and Medicare claims to evaluate the overall survival of patients with FL receiving 3 to 4 vs 5 to 6 cycles of bendamustine. Patients receiving 1 to 2 cycles of bendamustine chemotherapy were not included. Patients receiving 5 to 6 cycles of bendamustine were significantly younger (mean age, 75.0 vs 76.2 years; <em>P</em> < .01) and had fewer comorbidities by the NCI comorbidity index (mean score, 1.7 vs 2.0; <em>P</em> = .05) than those receiving 3 to 4 cycles of bendamustine, and on univariate analysis exhibited significantly lower risk of death (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.57-0.98; <em>P</em> = .04). However, multivariate analysis controlling for age and comorbidity did not reveal a significant association between overall survival and number of cycles of bendamustine (HR, 0.87; 95% CI, 0.66-1.15; <em>P</em> = .33). Limitations inherent to use of data such as these for causal inference are acknowledged. Nonetheless, these analyses suggest some older patients with FL achieve satisfactory survival outcomes even with lesser bendamustine exposure, and future efforts to prospectively identify such patients are warranted.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 3","pages":"Article 100019"},"PeriodicalIF":0.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000190/pdfft?md5=39bb4295030312550b540bb0e3d862e2&pid=1-s2.0-S2950328024000190-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141136987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-20DOI: 10.1016/j.bneo.2024.100020
Jun Y. Jiang , Chijioke Nze , Danielle Guffey , Rockbum Kim , Abiodun O. Oluyomi , Omar Rosales , Raka Bandyo , Courtney N. Miller-Chism , Mark M. Udden , Martha P. Mims , Hilary Ma , Gustavo A. Rivero , Akiva Diamond , Purnima S. Teegavarapu , Ang Li ∗ , Christopher R. Flowers ∗
Abstract
Real-world outcome data for patients with large B-cell lymphomas (LBCLs) who are uninsured or have socioeconomic barriers to care are limited. We performed a retrospective cohort study of patients with newly diagnosed LBCL treated in a large safety-net hospital system. Between January 2011 and June 2022, 496 patients aged >18 years were diagnosed with LBCL at Harris Health System, Houston, Texas. The median age was 53 years, 75% were uninsured, and 81% were in the most disadvantaged Area Deprivation Index national quartiles. Most (69%) had stage III/IV disease, 44% had poor-risk disease by the Revised International Prognostic Index (R-IPI), and 17% had a history of HIV infection. The median diagnosis-to-treatment interval was 17 days. The median follow-up time was 53.5 months. Among 464 evaluable patients, 66% achieved a complete response, and 11% had a partial response. Of 48 patients, 26 (54%) eligible for cell therapies received them. At 5 years, event-free and overall survival (OS) rates were 57% and 68%, respectively. Factors that affected OS included Hispanic ethnicity (hazard ratio [HR], 0.70; P = .027), R-IPI (HR, 4.67 for poor vs very good risk; P < .001), National Cancer Institute Comorbidity Index (HR, 1.53 per unit increment; P = .003), hemoglobin (HR, 0.89 per unit increment; P = .002), and International Normalized Ratio (HR, 2.17 per unit increment; P = .007). Insurance status was not associated with differences in OS. In our safety-net health system with robust financial assistance programs and limited access to cell therapies, uninsured status was not associated with inferior outcomes. Addressing barriers to care may improve outcomes in other settings.
{"title":"Clinical outcomes of patients with newly diagnosed large B-cell lymphoma in a safety-net hospital system","authors":"Jun Y. Jiang , Chijioke Nze , Danielle Guffey , Rockbum Kim , Abiodun O. Oluyomi , Omar Rosales , Raka Bandyo , Courtney N. Miller-Chism , Mark M. Udden , Martha P. Mims , Hilary Ma , Gustavo A. Rivero , Akiva Diamond , Purnima S. Teegavarapu , Ang Li ∗ , Christopher R. Flowers ∗","doi":"10.1016/j.bneo.2024.100020","DOIUrl":"10.1016/j.bneo.2024.100020","url":null,"abstract":"<div><h3>Abstract</h3><p>Real-world outcome data for patients with large B-cell lymphomas (LBCLs) who are uninsured or have socioeconomic barriers to care are limited. We performed a retrospective cohort study of patients with newly diagnosed LBCL treated in a large safety-net hospital system. Between January 2011 and June 2022, 496 patients aged >18 years were diagnosed with LBCL at Harris Health System, Houston, Texas. The median age was 53 years, 75% were uninsured, and 81% were in the most disadvantaged Area Deprivation Index national quartiles. Most (69%) had stage III/IV disease, 44% had poor-risk disease by the Revised International Prognostic Index (R-IPI), and 17% had a history of HIV infection. The median diagnosis-to-treatment interval was 17 days. The median follow-up time was 53.5 months. Among 464 evaluable patients, 66% achieved a complete response, and 11% had a partial response. Of 48 patients, 26 (54%) eligible for cell therapies received them. At 5 years, event-free and overall survival (OS) rates were 57% and 68%, respectively. Factors that affected OS included Hispanic ethnicity (hazard ratio [HR], 0.70; <em>P</em> = .027), R-IPI (HR, 4.67 for poor vs very good risk; <em>P</em> < .001), National Cancer Institute Comorbidity Index (HR, 1.53 per unit increment; <em>P</em> = .003), hemoglobin (HR, 0.89 per unit increment; <em>P</em> = .002), and International Normalized Ratio (HR, 2.17 per unit increment; <em>P</em> = .007). Insurance status was not associated with differences in OS. In our safety-net health system with robust financial assistance programs and limited access to cell therapies, uninsured status was not associated with inferior outcomes. Addressing barriers to care may improve outcomes in other settings.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 3","pages":"Article 100020"},"PeriodicalIF":0.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000207/pdfft?md5=e382f0d8e27c903ab9a7be1a0e9c73ff&pid=1-s2.0-S2950328024000207-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141144995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Glucocorticoids (GCs), such as dexamethasone and prednisone, are crucial components of B-cell precursor acute lymphoblastic leukemia (B-ALL) therapies. However, the molecular basis of GC-induced cell death remains elusive. Here, we show that GC suppresses mechanistic target of rapamycin complex 1 (mTORC1) signaling and that, conversely, oncogenic activation of mTORC1 confers resistance to GCs. Our genome-wide CRISPR/CRISPR-associated protein 9 (CRISPR/Cas9) dropout screens reveal that depletion of components of either the gap activity toward Rags 1 or tuberous sclerosis complexes, both negative regulators of mTORC1 signaling, significantly attenuates B-ALL cell sensitivity to dexamethasone. Dexamethasone primarily induces B-ALL cell death by downregulating mTORC1 activity, thus promoting autophagy and impairing protein synthesis. Dexamethasone treatment failed to suppress mTORC1 activity in B-ALL cells expressing mutant GC receptors lacking DNA-binding capacity, suggesting that dexamethasone transcriptionally represses mTORC1 activity. RNA-sequencing analysis identified multiple dexamethasone target genes that negatively regulate mTORC1 activity. Our findings suggest that GC sensitivity is significantly influenced by oncogenic stimuli and/or growth factors that activate the PI3K-AKT-mTORC1 pathway. This is consistent with the frequent GC resistance found in Ph and Ph-like ALLs.
{"title":"Central role of the mTORC1 pathway in glucocorticoid activity against B-ALL cells","authors":"Hiroshi Imanaga , Yuichiro Semba , Kensuke Sasaki , Kiyoko Setoguchi , Hillary Maniriho , Takuji Yamauchi , Tatsuya Terasaki , Shigeki Hirabayashi , Fumihiko Nakao , Jumpei Nogami , Shai Izraeli , Koichi Akashi , Takahiro Maeda","doi":"10.1016/j.bneo.2024.100015","DOIUrl":"https://doi.org/10.1016/j.bneo.2024.100015","url":null,"abstract":"<div><h3>Abstract</h3><p>Glucocorticoids (GCs), such as dexamethasone and prednisone, are crucial components of B-cell precursor acute lymphoblastic leukemia (B-ALL) therapies. However, the molecular basis of GC-induced cell death remains elusive. Here, we show that GC suppresses mechanistic target of rapamycin complex 1 (mTORC1) signaling and that, conversely, oncogenic activation of mTORC1 confers resistance to GCs. Our genome-wide CRISPR/CRISPR-associated protein 9 (CRISPR/Cas9) dropout screens reveal that depletion of components of either the gap activity toward Rags 1 or tuberous sclerosis complexes, both negative regulators of mTORC1 signaling, significantly attenuates B-ALL cell sensitivity to dexamethasone. Dexamethasone primarily induces B-ALL cell death by downregulating mTORC1 activity, thus promoting autophagy and impairing protein synthesis. Dexamethasone treatment failed to suppress mTORC1 activity in B-ALL cells expressing mutant GC receptors lacking DNA-binding capacity, suggesting that dexamethasone transcriptionally represses mTORC1 activity. RNA-sequencing analysis identified multiple dexamethasone target genes that negatively regulate mTORC1 activity. Our findings suggest that GC sensitivity is significantly influenced by oncogenic stimuli and/or growth factors that activate the PI3K-AKT-mTORC1 pathway. This is consistent with the frequent GC resistance found in Ph and Ph-like ALLs.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 2","pages":"Article 100015"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000153/pdfft?md5=ab04dd4c2a9ccc8ef49f43cf5cbbb31a&pid=1-s2.0-S2950328024000153-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141090068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-12DOI: 10.1016/j.bneo.2024.100010
Megan Metzger , Zachary M. Avigan , Pankit Vachhani , Julian Waksal , John Mascarenhas
Abstract
Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by constitutional symptoms, progressive cytopenias, and splenomegaly. Activating mutations in the JAK/STAT pathway and cytokine dysregulation driving bone marrow fibrosis and extramedullary hematopoiesis underlie the pathobiology of MF. Although multiple JAK inhibitors are currently approved and provide significant symptom improvement, these agents do not possess disease course modifying potential. Additionally, outcomes are poor for patients who fail JAK inhibitors, highlighting the need for novel mechanism-based therapies and innovative combination strategies. Selinexor, a novel Exportin 1 (XPO1) inhibitor that blocks nuclear export, increases nuclear localization and activity of p53 and other tumor suppressor pathways and decreases cytoplasmic activation of multiple proliferative and profibrotic pathways. Selinexor currently has approved indications in multiple myeloma and lymphoma, with broad potential applications in other malignancies, although it can be limited by toxicity in some settings. Selinexor has shown clinical activity and tolerability in MF, both as monotherapy and, particularly, in combination with ruxolitinib. The collective, early phase trial data support a phase 3 randomized, registration study of selinexor and ruxolitinib in patients with MF naïve to JAK inhibitor therapy. Further work is needed to elucidate the role of XPO1 inhibition as a potential disease-modifying strategy to improve outcomes in MF.
{"title":"A novel application of XPO1 inhibition for the treatment of myelofibrosis","authors":"Megan Metzger , Zachary M. Avigan , Pankit Vachhani , Julian Waksal , John Mascarenhas","doi":"10.1016/j.bneo.2024.100010","DOIUrl":"10.1016/j.bneo.2024.100010","url":null,"abstract":"<div><h3>Abstract</h3><p>Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by constitutional symptoms, progressive cytopenias, and splenomegaly. Activating mutations in the JAK/STAT pathway and cytokine dysregulation driving bone marrow fibrosis and extramedullary hematopoiesis underlie the pathobiology of MF. Although multiple JAK inhibitors are currently approved and provide significant symptom improvement, these agents do not possess disease course modifying potential. Additionally, outcomes are poor for patients who fail JAK inhibitors, highlighting the need for novel mechanism-based therapies and innovative combination strategies. Selinexor, a novel Exportin 1 (XPO1) inhibitor that blocks nuclear export, increases nuclear localization and activity of p53 and other tumor suppressor pathways and decreases cytoplasmic activation of multiple proliferative and profibrotic pathways. Selinexor currently has approved indications in multiple myeloma and lymphoma, with broad potential applications in other malignancies, although it can be limited by toxicity in some settings. Selinexor has shown clinical activity and tolerability in MF, both as monotherapy and, particularly, in combination with ruxolitinib. The collective, early phase trial data support a phase 3 randomized, registration study of selinexor and ruxolitinib in patients with MF naïve to JAK inhibitor therapy. Further work is needed to elucidate the role of XPO1 inhibition as a potential disease-modifying strategy to improve outcomes in MF.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 2","pages":"Article 100010"},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000104/pdfft?md5=ddc40a14d238e982837d9bb17da6c825&pid=1-s2.0-S2950328024000104-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140787629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-12DOI: 10.1016/j.bneo.2024.100012
Eli M. Soyfer , Jianhong C. Heidmann , Gajalakshmi Ramanathan , Hellen Nguyen , Simran Bhardwaj , Jane H. Chen , Yeowon Jung , Eshika Arora , Helen Huang , Lauren Chen , Aanya Amin , Eduard Mas Marin , W. Lucas Wadley , Hew Yeng Lai , Nahid Haghighi , Angela G. Fleischman
{"title":"Saliva as a feasible alternative to blood for interrogation of somatic hematopoietic variants","authors":"Eli M. Soyfer , Jianhong C. Heidmann , Gajalakshmi Ramanathan , Hellen Nguyen , Simran Bhardwaj , Jane H. Chen , Yeowon Jung , Eshika Arora , Helen Huang , Lauren Chen , Aanya Amin , Eduard Mas Marin , W. Lucas Wadley , Hew Yeng Lai , Nahid Haghighi , Angela G. Fleischman","doi":"10.1016/j.bneo.2024.100012","DOIUrl":"10.1016/j.bneo.2024.100012","url":null,"abstract":"","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 2","pages":"Article 100012"},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000128/pdfft?md5=9011b4acd7f6d26593a3ba3c30d89418&pid=1-s2.0-S2950328024000128-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140785997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-29DOI: 10.1016/j.bneo.2024.100009
Timothy S. Pardee , Bayard L. Powell , Richard A. Larson , Joseph Maly , Michael Keng , Matthew Foster , Eun-Ji Choi , Heinz Sill , Thomas Cluzeau , Deepa Jeyakumar , Olga Frankfurt , Prapti Patel , Michael Schuster , Elisabeth Koller , Regis Costello , Uwe Platzbecker , Pau Montesinos , Susana Vives , Aziz Nazha , Rachel Cook , Jorge Cortes
Abstract
Acute myeloid leukemia (AML) is an aggressive cancer of the myeloid lineage. Outcomes in older patients are poor, with high rates of resistant and relapsed disease. Devimistat is a lipoic acid analog that inhibits mitochondrial metabolism. Devimistat combined with high-dose cytarabine and mitoxantrone resulted in promising phase 1 and 2 response rates especially in older patients. Therefore, the phase 3 ARMADA 2000 trial was conducted in patients aged ≥50 years with relapsed or refractory AML. The study randomized patients between devimistat combined with high-dose cytarabine and mitoxantrone (CHAM) or 1 of 3 control treatment regimens without devimistat: high-dose cytarabine and mitoxantrone; mitoxantrone, etoposide, and cytarabine; or fludarabine, cytarabine, and filgrastim. Overall, 265 patients consented to participate from 56 sites across 11 countries, and 200 patients were randomized, 98 patients to the devimistat arm and 102 patients to the control arm. The safety profile was consistent with high-dose cytarabine–based salvage regimens. There were 18 (9%) deaths on study (11 on CHAM and 7 on control). The study failed to meet its primary end point, with a complete remission (CR) rate of 20.4% in the devimistat arm compared with 21.6% in the control arm (P = .57). Overall survival was not statistically significantly different between the study arms, with a median of 8.9 months in the CHAM arm compared with 6.2 months in the control arm (P = .62). In conclusion, devimistat added to chemotherapy did not improve the CR rate or survival in patients aged ≥50 years with relapsed or refractory AML. This trial was registered at www.ClinicalTrials.gov as #NCT03504410.
{"title":"Devimistat plus chemotherapy vs chemotherapy alone for older relapsed or refractory patients with AML: results of the ARMADA trial","authors":"Timothy S. Pardee , Bayard L. Powell , Richard A. Larson , Joseph Maly , Michael Keng , Matthew Foster , Eun-Ji Choi , Heinz Sill , Thomas Cluzeau , Deepa Jeyakumar , Olga Frankfurt , Prapti Patel , Michael Schuster , Elisabeth Koller , Regis Costello , Uwe Platzbecker , Pau Montesinos , Susana Vives , Aziz Nazha , Rachel Cook , Jorge Cortes","doi":"10.1016/j.bneo.2024.100009","DOIUrl":"10.1016/j.bneo.2024.100009","url":null,"abstract":"<div><h3>Abstract</h3><p>Acute myeloid leukemia (AML) is an aggressive cancer of the myeloid lineage. Outcomes in older patients are poor, with high rates of resistant and relapsed disease. Devimistat is a lipoic acid analog that inhibits mitochondrial metabolism. Devimistat combined with high-dose cytarabine and mitoxantrone resulted in promising phase 1 and 2 response rates especially in older patients. Therefore, the phase 3 ARMADA 2000 trial was conducted in patients aged ≥50 years with relapsed or refractory AML. The study randomized patients between devimistat combined with high-dose cytarabine and mitoxantrone (CHAM) or 1 of 3 control treatment regimens without devimistat: high-dose cytarabine and mitoxantrone; mitoxantrone, etoposide, and cytarabine; or fludarabine, cytarabine, and filgrastim. Overall, 265 patients consented to participate from 56 sites across 11 countries, and 200 patients were randomized, 98 patients to the devimistat arm and 102 patients to the control arm. The safety profile was consistent with high-dose cytarabine–based salvage regimens. There were 18 (9%) deaths on study (11 on CHAM and 7 on control). The study failed to meet its primary end point, with a complete remission (CR) rate of 20.4% in the devimistat arm compared with 21.6% in the control arm (<em>P</em> = .57). Overall survival was not statistically significantly different between the study arms, with a median of 8.9 months in the CHAM arm compared with 6.2 months in the control arm (<em>P</em> = .62). In conclusion, devimistat added to chemotherapy did not improve the CR rate or survival in patients aged ≥50 years with relapsed or refractory AML. This trial was registered at <span>www.ClinicalTrials.gov</span><svg><path></path></svg> as #NCT03504410.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 2","pages":"Article 100009"},"PeriodicalIF":0.0,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000098/pdfft?md5=8d5513d5e2eee809a51383d73851adc6&pid=1-s2.0-S2950328024000098-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140405002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guadecitabine (SGI-110) is a dinucleotide form of decitabine that has been studied in myelodysplastic syndrome (MDS) and acute myeloid leukemia. Here, we present the results of a single-center phase 2 trial of this agent for patients with higher-risk MDS or chronic myelomonocytic leukemia (CMML). Guadecitabine was administered at a dose of 60 mg/m2 subcutaneously for 5 days. Of 100 enrolled patients, 82% had MDS. The median age was 69 years, and International Prognostic Scoring System (IPSS) was intermediate-2 in 78% and high in 14%. Thirty-eight percent had complex cytogenetics, and 32% had TP53mut. By the International Working Group 2006 (IWG-2006) criteria, 25% achieved complete remission (CR), 30% marrow CR, and 33% no response (NR). Common grade 3 events were febrile neutropenia (32%) and infection (25%). Mortality rates at 4 and 8 weeks were 0% and 4%, respectively. The median overall survival (mOS) was 16.8 months. Patients who underwent transplantation (21%) had an mOS of 46.6 months. We then reanalyzed this data set using IPSS-Molecular (IPSS-M) and IWG-2023 response criteria. By IPSS-M, 60% of patients were classified as very high and 27% as high risk. By IWG-2023, overall response rate was 52%, with 30% CR, 14% CR with limited count recovery, and 42% NR. IPSS-M provided adequate risk stratification at enrollment. Patients classified as marrow CR had widely different outcomes when reclassified by IWG-2023. In conclusion, SGI-110 was active in high-risk MDS, but survival is unlikely to be superior to current hypomethylating agents. The study is registered at www.ClinicalTrials.gov as #NCT02131597.
{"title":"Prospective performance of the IWG-2023 criteria and IPSS-M in a phase 2 trial of guadecitabine for higher-risk MDS or CMML","authors":"Samuel Urrutia , Prithviraj Bose , Yesid Alvarado , Gautam Borthakur , Farhad Ravandi , Naval Daver , Naveen Pemmaraju , Elias Jabbour , Koichi Takahashi , Tapan Kadia , Courtney DiNardo , Steven Kornblau , Rashmi Kanagal-Shamanna , Xuelin Huang , Kristy Bodden , Hagop Kantarjian , Guillermo Garcia-Manero","doi":"10.1016/j.bneo.2024.100008","DOIUrl":"10.1016/j.bneo.2024.100008","url":null,"abstract":"<div><h3>Abstract</h3><p>Guadecitabine (SGI-110) is a dinucleotide form of decitabine that has been studied in myelodysplastic syndrome (MDS) and acute myeloid leukemia. Here, we present the results of a single-center phase 2 trial of this agent for patients with higher-risk MDS or chronic myelomonocytic leukemia (CMML). Guadecitabine was administered at a dose of 60 mg/m2 subcutaneously for 5 days. Of 100 enrolled patients, 82% had MDS. The median age was 69 years, and International Prognostic Scoring System (IPSS) was intermediate-2 in 78% and high in 14%. Thirty-eight percent had complex cytogenetics, and 32% had <em>TP53</em><sup><em>mut</em></sup>. By the International Working Group 2006 (IWG-2006) criteria, 25% achieved complete remission (CR), 30% marrow CR, and 33% no response (NR). Common grade 3 events were febrile neutropenia (32%) and infection (25%). Mortality rates at 4 and 8 weeks were 0% and 4%, respectively. The median overall survival (mOS) was 16.8 months. Patients who underwent transplantation (21%) had an mOS of 46.6 months. We then reanalyzed this data set using IPSS-Molecular (IPSS-M) and IWG-2023 response criteria. By IPSS-M, 60% of patients were classified as very high and 27% as high risk. By IWG-2023, overall response rate was 52%, with 30% CR, 14% CR with limited count recovery, and 42% NR. IPSS-M provided adequate risk stratification at enrollment. Patients classified as marrow CR had widely different outcomes when reclassified by IWG-2023. In conclusion, SGI-110 was active in high-risk MDS, but survival is unlikely to be superior to current hypomethylating agents. The study is registered at <span>www.ClinicalTrials.gov</span><svg><path></path></svg> as #NCT02131597.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 2","pages":"Article 100008"},"PeriodicalIF":0.0,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000086/pdfft?md5=7939e3a044510c2141a1112ae93823d1&pid=1-s2.0-S2950328024000086-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140402752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-29DOI: 10.1016/j.bneo.2024.100007
Wen-Kai Weng , Chaitanya Iragavarapu , Gavin M. Weng , Richard T. Hoppe , Susan Hiniker , Michael S. Khodadoust , Youn H. Kim
{"title":"Long-term remission with allogeneic transplant in patients with refractory/relapsed cutaneous cytotoxic T-cell lymphoma","authors":"Wen-Kai Weng , Chaitanya Iragavarapu , Gavin M. Weng , Richard T. Hoppe , Susan Hiniker , Michael S. Khodadoust , Youn H. Kim","doi":"10.1016/j.bneo.2024.100007","DOIUrl":"10.1016/j.bneo.2024.100007","url":null,"abstract":"","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 2","pages":"Article 100007"},"PeriodicalIF":0.0,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000074/pdfft?md5=2dd103e3b108c65386bc27ac3ce66988&pid=1-s2.0-S2950328024000074-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140402164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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