Pub Date : 2024-12-17DOI: 10.1038/s41375-024-02490-6
Nicole Seifert, Sarah Reinke, Johanna Grund, Berit Müller-Meinhard, Julia Richter, Thorsten Heilmann, Hans Schlößer, Michaela Kotrova, Monika Brüggemann, Peter Borchmann, Paul J. Bröckelmann, Michael Altenbuchinger, Wolfram Klapper
The Tumor Microenvironment (TME) in classical Hodgkin Lymphoma (HL) contains abundant immune cells and only few neoplastic Hodgkin and Reed-Sternberg cells (HRSC). We analyzed the T-cell receptor (TCR) repertoire to detect T-cell expansion in the TME and blood. In contrast to solid cancer tissue, T-cells in the TME of HL are highly polyclonal at first diagnosis and show only minor clonal expansion during anti-PD1 immune checkpoint blockade (ICB). At relapse and during ICB, pre-amplified T-cell populations increase in the TME of solid cancers but to a much lesser extent in HL. In contrast, T-cell populations in the peripheral blood of HL patients display higher clonality than healthy controls reaching clonality levels comparable to solid cancer. However, pre-amplified blood T-cells in HL patients show only minor additional clonal expansion during ICB. Moreover, blood-derived T-cells do not repopulate the TME of HL to the same extent as observed in solid cancers. Thus, the T-cell repertoire in the TME of HL appears unique by a relatively low clonal T-cell content and the exclusion of clonally expanded T-cells from the peripheral blood. Exclusion of clonally expanded tumor-specific T-cells from the TME may present a novel mechanism of immune evasion in HL.
经典霍奇金淋巴瘤（HL）的肿瘤微环境（TME）中含有大量免疫细胞，只有少数肿瘤性霍奇金细胞和里德-斯特恩伯格细胞（HRSC）。我们分析了T细胞受体（TCR）谱系，以检测TME和血液中T细胞的扩增情况。与实体瘤组织不同，HL的TME中的T细胞在初诊时高度多克隆，在抗PD1免疫检查点阻断（ICB）期间仅表现出轻微的克隆扩增。在复发和 ICB 期间，实体瘤 TME 中的预扩增 T 细胞群会增加，但在 HL 中增加的程度要小得多。相比之下，HL 患者外周血中的 T 细胞群的克隆度高于健康对照组，达到了与实体癌相当的克隆度水平。然而，HL 患者的预扩增血液 T 细胞在 ICB 期间仅表现出轻微的额外克隆扩增。此外，血液中的 T 细胞在 HL 的 TME 中的重新填充程度与实体瘤中观察到的不同。因此，HL 的 TME 中的 T 细胞谱似乎是独特的，其克隆 T 细胞含量相对较低，外周血中排除了克隆扩增的 T 细胞。将克隆扩增的肿瘤特异性T细胞排除在TME之外可能是HL免疫逃避的一种新机制。
{"title":"T-cell diversity and exclusion of blood-derived T-cells in the tumor microenvironment of classical Hodgkin Lymphoma","authors":"Nicole Seifert, Sarah Reinke, Johanna Grund, Berit Müller-Meinhard, Julia Richter, Thorsten Heilmann, Hans Schlößer, Michaela Kotrova, Monika Brüggemann, Peter Borchmann, Paul J. Bröckelmann, Michael Altenbuchinger, Wolfram Klapper","doi":"10.1038/s41375-024-02490-6","DOIUrl":"10.1038/s41375-024-02490-6","url":null,"abstract":"The Tumor Microenvironment (TME) in classical Hodgkin Lymphoma (HL) contains abundant immune cells and only few neoplastic Hodgkin and Reed-Sternberg cells (HRSC). We analyzed the T-cell receptor (TCR) repertoire to detect T-cell expansion in the TME and blood. In contrast to solid cancer tissue, T-cells in the TME of HL are highly polyclonal at first diagnosis and show only minor clonal expansion during anti-PD1 immune checkpoint blockade (ICB). At relapse and during ICB, pre-amplified T-cell populations increase in the TME of solid cancers but to a much lesser extent in HL. In contrast, T-cell populations in the peripheral blood of HL patients display higher clonality than healthy controls reaching clonality levels comparable to solid cancer. However, pre-amplified blood T-cells in HL patients show only minor additional clonal expansion during ICB. Moreover, blood-derived T-cells do not repopulate the TME of HL to the same extent as observed in solid cancers. Thus, the T-cell repertoire in the TME of HL appears unique by a relatively low clonal T-cell content and the exclusion of clonally expanded T-cells from the peripheral blood. Exclusion of clonally expanded tumor-specific T-cells from the TME may present a novel mechanism of immune evasion in HL.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 3","pages":"684-693"},"PeriodicalIF":12.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02490-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142832007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-16DOI: 10.1038/s41375-024-02493-3
Tommaso Balestra, Lisa M Niswander, Asen Bagashev, Joseph P Loftus, Savannah L Ross, Robert K Chen, Samantha M McClellan, Jacob J Junco, Diego A Bárcenas López, Karen R. Rabin, Terry J Fry, Sarah K Tasian
CRLF2 rearrangements occur in >50% of Ph-like and Down syndrome (DS)-associated B-acute lymphoblastic leukemia (ALL) and induce constitutive kinase signaling targetable by the JAK1/2 inhibitor ruxolitinib under current clinical investigation. While chimeric antigen receptor T cell (CART) immunotherapies have achieved remarkable remission rates in children with relapsed/refractory B-ALL, ~50% of CD19CART-treated patients relapse again, many with CD19 antigen loss. We previously reported preclinical activity of thymic stromal lymphopoietin receptor-targeted cellular immunotherapy (TSLPRCART) against CRLF2-overexpressing ALL as an alternative approach. In this study, we posited that combinatorial TSLPRCART and ruxolitinib would have superior activity and first validated potent TSLPRCART-induced inhibition of leukemia proliferation in vitro in CRLF2-rearranged ALL cell lines and in vivo in Ph-like and DS-ALL patient-derived xenograft (PDX) models. However, simultaneous TSLPRCART/ruxolitinib or CD19CART/ruxolitinib treatment during initial CART expansion diminished T cell proliferation, blunted cytokine production, and/or facilitated leukemia relapse, which was abrogated by time-sequenced/delayed ruxolitinib co-exposure. Importantly, ruxolitinib co-administration prevented fatal TSLPRCART cytokine-associated toxicity in ALL PDX mice. Upon ruxolitinib withdrawal, TSLPRCART functionality recovered in vivo with clearance of subsequent ALL rechallenge. These translational studies demonstrate an effective two-pronged therapeutic strategy that mitigates acute CART-induced hyperinflammation and provides potential anti-leukemia ‘maintenance’ relapse prevention for CRLF2-rearranged Ph-like and DS-ALL.
{"title":"Co-targeting of the thymic stromal lymphopoietin receptor to decrease immunotherapeutic resistance in CRLF2-rearranged Ph-like and Down syndrome acute lymphoblastic leukemia","authors":"Tommaso Balestra, Lisa M Niswander, Asen Bagashev, Joseph P Loftus, Savannah L Ross, Robert K Chen, Samantha M McClellan, Jacob J Junco, Diego A Bárcenas López, Karen R. Rabin, Terry J Fry, Sarah K Tasian","doi":"10.1038/s41375-024-02493-3","DOIUrl":"10.1038/s41375-024-02493-3","url":null,"abstract":"CRLF2 rearrangements occur in >50% of Ph-like and Down syndrome (DS)-associated B-acute lymphoblastic leukemia (ALL) and induce constitutive kinase signaling targetable by the JAK1/2 inhibitor ruxolitinib under current clinical investigation. While chimeric antigen receptor T cell (CART) immunotherapies have achieved remarkable remission rates in children with relapsed/refractory B-ALL, ~50% of CD19CART-treated patients relapse again, many with CD19 antigen loss. We previously reported preclinical activity of thymic stromal lymphopoietin receptor-targeted cellular immunotherapy (TSLPRCART) against CRLF2-overexpressing ALL as an alternative approach. In this study, we posited that combinatorial TSLPRCART and ruxolitinib would have superior activity and first validated potent TSLPRCART-induced inhibition of leukemia proliferation in vitro in CRLF2-rearranged ALL cell lines and in vivo in Ph-like and DS-ALL patient-derived xenograft (PDX) models. However, simultaneous TSLPRCART/ruxolitinib or CD19CART/ruxolitinib treatment during initial CART expansion diminished T cell proliferation, blunted cytokine production, and/or facilitated leukemia relapse, which was abrogated by time-sequenced/delayed ruxolitinib co-exposure. Importantly, ruxolitinib co-administration prevented fatal TSLPRCART cytokine-associated toxicity in ALL PDX mice. Upon ruxolitinib withdrawal, TSLPRCART functionality recovered in vivo with clearance of subsequent ALL rechallenge. These translational studies demonstrate an effective two-pronged therapeutic strategy that mitigates acute CART-induced hyperinflammation and provides potential anti-leukemia ‘maintenance’ relapse prevention for CRLF2-rearranged Ph-like and DS-ALL.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 3","pages":"555-567"},"PeriodicalIF":12.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02493-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-16DOI: 10.1038/s41375-024-02489-z
Kenzie Lee, Taxiarchis Kourelis, Marcella Tschautscher, Rahma Warsame, Francis Buadi, Morie Gertz, Eli Muchtar, David Dingli, Suzanne Hayman, Ronald Go, Lisa Hwa, Amie Fonder, Wilson Gonsalves, Miriam Hobbs, Robert Kyle, Prashant Kapoor, Nelson Leung, Moritz Binder, Joselle Cook, Yi Lin, Michelle Rogers, S. Vincent Rajkumar, Shaji Kumar, Angela Dispenzieri
Cause of death (COD) in POEMS (polyneuropathy, organomegaly, endocrinopathies, monoclonal protein and skin changes) syndrome is not well described. We investigated COD in patients with POEMS syndrome treated at Mayo Clinic between 2000 and 2022. Of the 89 deaths, 49 patients had known COD and were the subject of this study. Seventeen patients died of unrelated causes, while 32 patients (65%) died from causes related to POEMS syndrome including secondary malignancies like myelodysplastic syndrome and acute leukemia (n = 5) and complications from active therapy (n = 5). Notably, 19 patients died with a stereotypic syndrome we termed capillary leak phenotype (CLP), which was characterized by refractory ascites, effusions and/or anasarca that ultimately resulted in hypotension, renal failure and cardiopulmonary arrest. Alternate causes for these symptoms, such as cardiac and hepatic etiologies, were excluded. CLP as a COD was an earlier event with a median time from diagnosis to death of 2.5 years compared to 12.0 years for all other deceased patients (p = <0.0001). By definition, treatment of terminal CLP was unsuccessful with median survival of only 4 months after CLP onset. The driver of CLP is unknown, but recognition as an entity should allow for systematic study.
{"title":"Capillary leak phenotype as a major cause of death in patients with POEMS syndrome","authors":"Kenzie Lee, Taxiarchis Kourelis, Marcella Tschautscher, Rahma Warsame, Francis Buadi, Morie Gertz, Eli Muchtar, David Dingli, Suzanne Hayman, Ronald Go, Lisa Hwa, Amie Fonder, Wilson Gonsalves, Miriam Hobbs, Robert Kyle, Prashant Kapoor, Nelson Leung, Moritz Binder, Joselle Cook, Yi Lin, Michelle Rogers, S. Vincent Rajkumar, Shaji Kumar, Angela Dispenzieri","doi":"10.1038/s41375-024-02489-z","DOIUrl":"10.1038/s41375-024-02489-z","url":null,"abstract":"Cause of death (COD) in POEMS (polyneuropathy, organomegaly, endocrinopathies, monoclonal protein and skin changes) syndrome is not well described. We investigated COD in patients with POEMS syndrome treated at Mayo Clinic between 2000 and 2022. Of the 89 deaths, 49 patients had known COD and were the subject of this study. Seventeen patients died of unrelated causes, while 32 patients (65%) died from causes related to POEMS syndrome including secondary malignancies like myelodysplastic syndrome and acute leukemia (n = 5) and complications from active therapy (n = 5). Notably, 19 patients died with a stereotypic syndrome we termed capillary leak phenotype (CLP), which was characterized by refractory ascites, effusions and/or anasarca that ultimately resulted in hypotension, renal failure and cardiopulmonary arrest. Alternate causes for these symptoms, such as cardiac and hepatic etiologies, were excluded. CLP as a COD was an earlier event with a median time from diagnosis to death of 2.5 years compared to 12.0 years for all other deceased patients (p = <0.0001). By definition, treatment of terminal CLP was unsuccessful with median survival of only 4 months after CLP onset. The driver of CLP is unknown, but recognition as an entity should allow for systematic study.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 3","pages":"703-709"},"PeriodicalIF":12.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02489-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-13DOI: 10.1038/s41375-024-02465-7
RP Gale, A. Hochhaus
{"title":"Mpox in people with haematological cancers","authors":"RP Gale, A. Hochhaus","doi":"10.1038/s41375-024-02465-7","DOIUrl":"10.1038/s41375-024-02465-7","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"275-275"},"PeriodicalIF":12.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02465-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-12DOI: 10.1038/s41375-024-02497-z
Corentin Orvain, Filippo Milano, Eduardo Rodríguez-Arbolí, Megan Othus, Effie W. Petersdorf, Brenda M. Sandmaier, Frederick R. Appelbaum, Roland B. Walter
Lack of HLA-matched related/unrelated donor remains a barrier to allogeneic hematopoietic cell transplantation (HCT) for adult acute myeloid leukemia (AML), with ongoing uncertainty about optimal donor type if more than one alternative donor is available. To assess the relationship between donor type, pre-HCT measurable residual disease (MRD), and post-HCT outcomes, we retrospectively analyzed 1265 myelodysplastic neoplasm (MDS)/AML and AML patients allografted in first or second remission with an HLA-matched sibling (MSD) or unrelated donor (MUD), HLA-mismatched unrelated donor (MMD), an HLA-haploidentical donor, or umbilical cord blood (UCB) at a single institution. Relapse risk was non-significantly higher after HLA-haploidentical and lower after UCB HCT. Non-relapse mortality (NRM) was significantly higher in patients undergoing MMD HCT, HLA-haploidentical HCT, and UCB, translating into significantly lower relapse-free survival (RFS) and overall survival for MMD and HLA-haploidentical HCT. There was a significant interaction between conditioning intensity and post-HCT outcomes for UCB HCT with better RFS for UCB HCT after MAC but higher NRM after non-MAC. In patients with pre-HCT MRD receiving MAC, relapse risk was significantly lower and RFS higher in those who underwent UCB HCT in comparison to MSD/MUD. Together, UCB HCT is a valuable alternative for MAC HCT, particularly in patients with pre-HCT MRD.
{"title":"Relationship between donor source, pre-transplant measurable residual disease, and outcome after allografting for adults with acute myeloid leukemia","authors":"Corentin Orvain, Filippo Milano, Eduardo Rodríguez-Arbolí, Megan Othus, Effie W. Petersdorf, Brenda M. Sandmaier, Frederick R. Appelbaum, Roland B. Walter","doi":"10.1038/s41375-024-02497-z","DOIUrl":"10.1038/s41375-024-02497-z","url":null,"abstract":"Lack of HLA-matched related/unrelated donor remains a barrier to allogeneic hematopoietic cell transplantation (HCT) for adult acute myeloid leukemia (AML), with ongoing uncertainty about optimal donor type if more than one alternative donor is available. To assess the relationship between donor type, pre-HCT measurable residual disease (MRD), and post-HCT outcomes, we retrospectively analyzed 1265 myelodysplastic neoplasm (MDS)/AML and AML patients allografted in first or second remission with an HLA-matched sibling (MSD) or unrelated donor (MUD), HLA-mismatched unrelated donor (MMD), an HLA-haploidentical donor, or umbilical cord blood (UCB) at a single institution. Relapse risk was non-significantly higher after HLA-haploidentical and lower after UCB HCT. Non-relapse mortality (NRM) was significantly higher in patients undergoing MMD HCT, HLA-haploidentical HCT, and UCB, translating into significantly lower relapse-free survival (RFS) and overall survival for MMD and HLA-haploidentical HCT. There was a significant interaction between conditioning intensity and post-HCT outcomes for UCB HCT with better RFS for UCB HCT after MAC but higher NRM after non-MAC. In patients with pre-HCT MRD receiving MAC, relapse risk was significantly lower and RFS higher in those who underwent UCB HCT in comparison to MSD/MUD. Together, UCB HCT is a valuable alternative for MAC HCT, particularly in patients with pre-HCT MRD.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"381-390"},"PeriodicalIF":12.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02497-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-12DOI: 10.1038/s41375-024-02470-w
Mylène Gerritsen, Florentien E. M. in ’t Hout, Ruth Knops, Bas L. R. Mandos, Melanie Decker, Tim Ripperger, Bert A. van der Reijden, Joost H. A. Martens, Joop H. Jansen
{"title":"Acute myeloid leukemia associated RUNX1 variants induce aberrant expression of transcription factor TCF4","authors":"Mylène Gerritsen, Florentien E. M. in ’t Hout, Ruth Knops, Bas L. R. Mandos, Melanie Decker, Tim Ripperger, Bert A. van der Reijden, Joost H. A. Martens, Joop H. Jansen","doi":"10.1038/s41375-024-02470-w","DOIUrl":"10.1038/s41375-024-02470-w","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"520-523"},"PeriodicalIF":12.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-11DOI: 10.1038/s41375-024-02474-6
Eleni A. Argyriadi, Ingo G. Steffen, Christiane Chen-Santel, Andrej Lissat, Andishe Attarbaschi, Jean-Pierre Bourquin, Guenter Henze, Arend von Stackelberg
Relapsed Acute Lymphoblastic Leukemia (ALL) is among the most common causes of cancer-associated deaths in children. However, little is known about the implications of deviations from ALL treatment protocols on survival rates. The present study elucidates the various characteristics of treatment deviations in children with relapsed ALL included in the ALL-REZ BFM 2002 (i.e., Relapse Berlin-Frankfurt- Münster) trial and determines their prognostic relevance for relapse and death rates. Among 687 patients, 100 were identified with treatment deviations, further classified, and examined by occurrence time, cause and type. Protocol deviation was considered a time-dependent variable and its impact on Disease Free Survival (DFS) and Overall Survival (OS) was examined using the time-dependent model Mantel Byar. Five years after the relapse diagnosis, deviations were significantly related to both inferior DFS (38%) and OS (57%) rates compared to protocol conformed treatment (DFS = 61%; OS = 70%, P < 0.001). Based on multivariate analyses, protocol deviation proved to be an independent adverse prognostic factor of DFS. Moreover, deviations triggered by chemotherapy-induced toxicity were associated with a higher relapse rate compared to deviations due to insufficient response. Therefore, to avoid impairment of results by deviations, future clinical trials, and treatment strategies should focus on less toxic treatments and stricter protocol compliance.
{"title":"Prognostic relevance of treatment deviations in children with relapsed acute lymphoblastic leukemia who were treated in the ALL-REZ BFM 2002 study","authors":"Eleni A. Argyriadi, Ingo G. Steffen, Christiane Chen-Santel, Andrej Lissat, Andishe Attarbaschi, Jean-Pierre Bourquin, Guenter Henze, Arend von Stackelberg","doi":"10.1038/s41375-024-02474-6","DOIUrl":"10.1038/s41375-024-02474-6","url":null,"abstract":"Relapsed Acute Lymphoblastic Leukemia (ALL) is among the most common causes of cancer-associated deaths in children. However, little is known about the implications of deviations from ALL treatment protocols on survival rates. The present study elucidates the various characteristics of treatment deviations in children with relapsed ALL included in the ALL-REZ BFM 2002 (i.e., Relapse Berlin-Frankfurt- Münster) trial and determines their prognostic relevance for relapse and death rates. Among 687 patients, 100 were identified with treatment deviations, further classified, and examined by occurrence time, cause and type. Protocol deviation was considered a time-dependent variable and its impact on Disease Free Survival (DFS) and Overall Survival (OS) was examined using the time-dependent model Mantel Byar. Five years after the relapse diagnosis, deviations were significantly related to both inferior DFS (38%) and OS (57%) rates compared to protocol conformed treatment (DFS = 61%; OS = 70%, P < 0.001). Based on multivariate analyses, protocol deviation proved to be an independent adverse prognostic factor of DFS. Moreover, deviations triggered by chemotherapy-induced toxicity were associated with a higher relapse rate compared to deviations due to insufficient response. Therefore, to avoid impairment of results by deviations, future clinical trials, and treatment strategies should focus on less toxic treatments and stricter protocol compliance.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"337-345"},"PeriodicalIF":12.8,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02474-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-10DOI: 10.1038/s41375-024-02483-5
Florian Simon, Othman Al-Sawaf, John F. Seymour, Barbara Eichhorst
Indolent mature B-cell neoplasms are a group of diseases in which recent therapeutic advances have led to an improved overall survival (OS) extending beyond several years. While cause of celebration for patients and caregivers, the increasingly long observation periods necessary to capture treatment effects are complicating trial design and possibly hindering swift access to more effective therapies. Surrogate endpoints are a tool with the potential of earlier study readouts, however, their validity needs to be proven in each individual disease and therapeutic setting. The validation of surrogate endpoints and available data for mature B-cell neoplasms are discussed within this perspective article, followed by an outlook on the potential of precise tools such as measurable residual disease assessment as novel surrogate candidates.
{"title":"Surrogate endpoints in mature B-cell neoplasms – meaningful or misleading?","authors":"Florian Simon, Othman Al-Sawaf, John F. Seymour, Barbara Eichhorst","doi":"10.1038/s41375-024-02483-5","DOIUrl":"10.1038/s41375-024-02483-5","url":null,"abstract":"Indolent mature B-cell neoplasms are a group of diseases in which recent therapeutic advances have led to an improved overall survival (OS) extending beyond several years. While cause of celebration for patients and caregivers, the increasingly long observation periods necessary to capture treatment effects are complicating trial design and possibly hindering swift access to more effective therapies. Surrogate endpoints are a tool with the potential of earlier study readouts, however, their validity needs to be proven in each individual disease and therapeutic setting. The validation of surrogate endpoints and available data for mature B-cell neoplasms are discussed within this perspective article, followed by an outlook on the potential of precise tools such as measurable residual disease assessment as novel surrogate candidates.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 1","pages":"25-28"},"PeriodicalIF":12.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02483-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-10DOI: 10.1038/s41375-024-02492-4
Paul J. Hampel, Kari G. Rabe, Yucai Wang, Steven R. Hwang, Saad S. Kenderian, Eli Muchtar, Jose F. Leis, Amber B. Koehler, Mazie Tsang, Talal Hilal, Ricardo Parrondo, Rachel J. Bailen, Susan M. Schwager, Curtis A. Hanson, Esteban Braggio, Susan L. Slager, Min Shi, Cinthya J. Zepeda-Mendoza, Daniel L. Van Dyke, Tait D. Shanafelt, Rebecca L. King, Timothy G. Call, Neil E. Kay, Wei Ding, Sameer A. Parikh
{"title":"Incidence of Richter transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma in the targeted therapy era","authors":"Paul J. Hampel, Kari G. Rabe, Yucai Wang, Steven R. Hwang, Saad S. Kenderian, Eli Muchtar, Jose F. Leis, Amber B. Koehler, Mazie Tsang, Talal Hilal, Ricardo Parrondo, Rachel J. Bailen, Susan M. Schwager, Curtis A. Hanson, Esteban Braggio, Susan L. Slager, Min Shi, Cinthya J. Zepeda-Mendoza, Daniel L. Van Dyke, Tait D. Shanafelt, Rebecca L. King, Timothy G. Call, Neil E. Kay, Wei Ding, Sameer A. Parikh","doi":"10.1038/s41375-024-02492-4","DOIUrl":"10.1038/s41375-024-02492-4","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"503-507"},"PeriodicalIF":12.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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