Pub Date : 2025-01-05DOI: 10.1080/10428194.2024.2446617
Gaurav Varma, Lindsay Fogel, Beth Gordon, Mateo Mejia Saldarriaga, Jaeil Ahn, Adolfo Aleman, Jessica Caro, Maya C Rosenberg, Jorge Monge, Harsh Parmar, David Kaminetzky, Tibor Moskovits, David S Siegel, Gareth J Morgan, Ruben Niesvizky, Faith E Davies, Noa Biran
Patients participating in clinical trials are highly selected and may not represent the general population. The pivotal study of teclistamab (MajesTEC-1), a B-cell maturation antigen (BCMA)xCD3 bispecific antibody, demonstrated impressive response rates and progression free survival in relapsed/refractory multiple myeloma (RRMM) with acceptable toxicity. We performed a retrospective study of 58 patients treated as standard of care at four US academic centers to determine how these results translated to the real-world. Most patients (87.9%) would not have been eligible for the MajesTEC-1 study due to either disease related factors, patient related comorbidities or socio-economic/geographical factors. Despite these 'less-favorable' characteristics we observed similar efficacy and toxicity to MajesTEC-1. A meta-analysis with six other published real-world series (n = 546) confirmed these results. These data support the significant clinical activity of teclistamab in RRMM and highlights the importance of real-world data to accompany the pivotal trial data to further inform daily clinical practice.
{"title":"Real-world safety and efficacy of teclistamab in relapsed/refractory multiple myeloma: results from a multicenter, retrospective study and descriptive meta-analysis.","authors":"Gaurav Varma, Lindsay Fogel, Beth Gordon, Mateo Mejia Saldarriaga, Jaeil Ahn, Adolfo Aleman, Jessica Caro, Maya C Rosenberg, Jorge Monge, Harsh Parmar, David Kaminetzky, Tibor Moskovits, David S Siegel, Gareth J Morgan, Ruben Niesvizky, Faith E Davies, Noa Biran","doi":"10.1080/10428194.2024.2446617","DOIUrl":"https://doi.org/10.1080/10428194.2024.2446617","url":null,"abstract":"<p><p>Patients participating in clinical trials are highly selected and may not represent the general population. The pivotal study of teclistamab (MajesTEC-1), a B-cell maturation antigen (BCMA)xCD3 bispecific antibody, demonstrated impressive response rates and progression free survival in relapsed/refractory multiple myeloma (RRMM) with acceptable toxicity. We performed a retrospective study of 58 patients treated as standard of care at four US academic centers to determine how these results translated to the real-world. Most patients (87.9%) would not have been eligible for the MajesTEC-1 study due to either disease related factors, patient related comorbidities or socio-economic/geographical factors. Despite these 'less-favorable' characteristics we observed similar efficacy and toxicity to MajesTEC-1. A meta-analysis with six other published real-world series (n = 546) confirmed these results. These data support the significant clinical activity of teclistamab in RRMM and highlights the importance of real-world data to accompany the pivotal trial data to further inform daily clinical practice.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":" ","pages":"1-10"},"PeriodicalIF":2.2,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-05DOI: 10.1080/10428194.2024.2447371
Efrat Luttwak, Anita Kumar, Gilles Salles
Follicular lymphoma (FL) represents the second most frequent type of non-Hodgkin lymphoma and the most common indolent histology. The disease course of FL is heterogeneous, likely resulting from diverse molecular and immunological features that drive a broad spectrum of clinical presentations. While some patients with low-volume and asymptomatic disease are suitable for observation, patients with high tumor burden, advanced-stage, or symptomatic disease more often necessitate treatment initiation. The decision to begin therapy is personalized and typically initiated when GELF criteria are met. The introduction of novel agents has modified the treatment landscape for FL, allowing for more personalized strategies based on the specific characteristics of patients and diseases. In this review, we discuss the indications for treatment initiation and optimization, focusing on long-term follow-up of pivotal studies and emerging non-chemotherapy regimens. We further consider effective novel combination regimens and future directions for the evolution of frontline immunotherapy for the treatment of patients with FL.
{"title":"Advances in the treatment of high burden Follicular lymphoma: a Comprehensive review.","authors":"Efrat Luttwak, Anita Kumar, Gilles Salles","doi":"10.1080/10428194.2024.2447371","DOIUrl":"https://doi.org/10.1080/10428194.2024.2447371","url":null,"abstract":"<p><p>Follicular lymphoma (FL) represents the second most frequent type of non-Hodgkin lymphoma and the most common indolent histology. The disease course of FL is heterogeneous, likely resulting from diverse molecular and immunological features that drive a broad spectrum of clinical presentations. While some patients with low-volume and asymptomatic disease are suitable for observation, patients with high tumor burden, advanced-stage, or symptomatic disease more often necessitate treatment initiation. The decision to begin therapy is personalized and typically initiated when GELF criteria are met. The introduction of novel agents has modified the treatment landscape for FL, allowing for more personalized strategies based on the specific characteristics of patients and diseases. In this review, we discuss the indications for treatment initiation and optimization, focusing on long-term follow-up of pivotal studies and emerging non-chemotherapy regimens. We further consider effective novel combination regimens and future directions for the evolution of frontline immunotherapy for the treatment of patients with FL.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":" ","pages":"1-12"},"PeriodicalIF":2.2,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This retrospective study aimed to evaluate the efficacy and safety of PBVD (pegylated liposomal doxorubicin [PLD], bleomycin, vinblastine, and dacarbazine) in the first-line treatment of classical Hodgkin lymphoma (cHL) patients with cardiovascular risk factors. Overall, 84 patients (53 had stage I-II and 31 had stage III-IV disease) received PBVD. The median PLD treatment duration was 16 weeks (interquartile range [IQR]: 8-24) for stage I-II and 24 weeks (IQR: 12-24) for stage III-IV. Among them, 56 (66.7%) received radiotherapy (45 with stage I-II and 11 with stage III-IV disease). Seventy-four (88.1%) patients achieved complete response. At a median follow-up of 49.7 months, 2- and 5-year progression-free survival were both 83.2%, and overall survival was 98.7% and 94.9%. Adverse events occurred in 73.8% of patients, including 7.1% cardiac events. No treatment-related deaths were observed. This approach showed a favorable benefit-to-risk profile in this population.
{"title":"PBVD regimen (pegylated liposomal doxorubicin, bleomycin, vincristine, dacarbazine) in classical Hodgkin lymphoma patients with cardiovascular risk factors: a retrospective study.","authors":"Jia Jin, Dan-Dan Meng, Yu Wen, Qun-Ling Zhang, Fang-Fang Lv, Guang-Liang Chen, Xue-Jun Ma, Bao-Hua Yu, Sheng-Jian Zhang, Chang Liu, Zu-Guang Xia","doi":"10.1080/10428194.2024.2447888","DOIUrl":"https://doi.org/10.1080/10428194.2024.2447888","url":null,"abstract":"<p><p>This retrospective study aimed to evaluate the efficacy and safety of PBVD (pegylated liposomal doxorubicin [PLD], bleomycin, vinblastine, and dacarbazine) in the first-line treatment of classical Hodgkin lymphoma (cHL) patients with cardiovascular risk factors. Overall, 84 patients (53 had stage I-II and 31 had stage III-IV disease) received PBVD. The median PLD treatment duration was 16 weeks (interquartile range [IQR]: 8-24) for stage I-II and 24 weeks (IQR: 12-24) for stage III-IV. Among them, 56 (66.7%) received radiotherapy (45 with stage I-II and 11 with stage III-IV disease). Seventy-four (88.1%) patients achieved complete response. At a median follow-up of 49.7 months, 2- and 5-year progression-free survival were both 83.2%, and overall survival was 98.7% and 94.9%. Adverse events occurred in 73.8% of patients, including 7.1% cardiac events. No treatment-related deaths were observed. This approach showed a favorable benefit-to-risk profile in this population.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":" ","pages":"1-10"},"PeriodicalIF":2.2,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-03DOI: 10.1080/10428194.2024.2447882
Pedro Martins Almeida, Thomas Relander, Ola Linden
{"title":"Salvage therapy for Burkitt lymphoma with glofitamab: a case report.","authors":"Pedro Martins Almeida, Thomas Relander, Ola Linden","doi":"10.1080/10428194.2024.2447882","DOIUrl":"https://doi.org/10.1080/10428194.2024.2447882","url":null,"abstract":"","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":" ","pages":"1-4"},"PeriodicalIF":2.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-02DOI: 10.1080/10428194.2024.2447362
Loic Ysebaert, Pierre-Luc Mouchel, Camille Laurent, Anne Quillet-Mary
In this review, we focus on the pro-oncogene MYC, the modes of deregulation in mouse and human B-cells, its undisputable importance in the evaluation of biological prognostication of patients, but also how it impacts on response to modern therapeutics, and how it should be targeted to improve the overall survival of chronic lymphocytic lymphoma (CLL) patients. After an overview of the current understanding of the molecular dysregulation of c-MYC, we will show how CLL, both in its indolent and transformed phases, has developed among other B-cell lymphomas a tight regulation of its expression through the chronic activation of B-Cell Receptors (among others). This is particularly important if one desires to understand the mechanisms at stake in the over-expression of c-MYC especially in the lymph nodes compartment. So doing, we will show how this oncogene orchestrates pivotal cellular functions such as metabolism, drug resistance, proliferation and histologic transformation (Richter syndrome).
{"title":"The multi-faceted roles of MYC in the prognosis of chronic lymphocytic leukemia.","authors":"Loic Ysebaert, Pierre-Luc Mouchel, Camille Laurent, Anne Quillet-Mary","doi":"10.1080/10428194.2024.2447362","DOIUrl":"https://doi.org/10.1080/10428194.2024.2447362","url":null,"abstract":"<p><p>In this review, we focus on the pro-oncogene MYC, the modes of deregulation in mouse and human B-cells, its undisputable importance in the evaluation of biological prognostication of patients, but also how it impacts on response to modern therapeutics, and how it should be targeted to improve the overall survival of chronic lymphocytic lymphoma (CLL) patients. After an overview of the current understanding of the molecular dysregulation of c-MYC, we will show how CLL, both in its indolent and transformed phases, has developed among other B-cell lymphomas a tight regulation of its expression through the chronic activation of B-Cell Receptors (among others). This is particularly important if one desires to understand the mechanisms at stake in the over-expression of c-MYC especially in the lymph nodes compartment. So doing, we will show how this oncogene orchestrates pivotal cellular functions such as metabolism, drug resistance, proliferation and histologic transformation (Richter syndrome).</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":" ","pages":"1-13"},"PeriodicalIF":2.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-02DOI: 10.1080/10428194.2024.2447886
Dennis A Eichenauer, Peter Borchmann
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity accounting for ≈5% of all Hodgkin lymphoma (HL) cases. As some characteristics of NLPHL resemble B-cell non-Hodgkin lymphoma (B-NHL), nodular lymphocyte-predominant B-cell lymphoma has been proposed as alternative name. Unlike classical HL (cHL), NLPHL is mostly diagnosed in early stages. The clinical course is usually indolent. Overall, NLPHL patients have an excellent prognosis and the majority experiences long-term survival. Except for stage IA disease which is sufficiently treated with radiotherapy alone, treatment of newly diagnosed NLPHL is often very similar to cHL. However, activity has also been demonstrated for rituximab-containing protocols applied in B-NHL. Second-line treatment is chosen individually and mostly less intensive than in cHL. Chimeric antigen receptor T-cell therapy and bispecific antibodies may be part of future treatment strategies for NLPHL. This review aims at summarizing recent data on treatment approaches and discussing future perspectives in NLPHL.
{"title":"Nodular lymphocyte-predominant Hodgkin lymphoma revisited: current management strategies and future perspectives.","authors":"Dennis A Eichenauer, Peter Borchmann","doi":"10.1080/10428194.2024.2447886","DOIUrl":"https://doi.org/10.1080/10428194.2024.2447886","url":null,"abstract":"<p><p>Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity accounting for ≈5% of all Hodgkin lymphoma (HL) cases. As some characteristics of NLPHL resemble B-cell non-Hodgkin lymphoma (B-NHL), nodular lymphocyte-predominant B-cell lymphoma has been proposed as alternative name. Unlike classical HL (cHL), NLPHL is mostly diagnosed in early stages. The clinical course is usually indolent. Overall, NLPHL patients have an excellent prognosis and the majority experiences long-term survival. Except for stage IA disease which is sufficiently treated with radiotherapy alone, treatment of newly diagnosed NLPHL is often very similar to cHL. However, activity has also been demonstrated for rituximab-containing protocols applied in B-NHL. Second-line treatment is chosen individually and mostly less intensive than in cHL. Chimeric antigen receptor T-cell therapy and bispecific antibodies may be part of future treatment strategies for NLPHL. This review aims at summarizing recent data on treatment approaches and discussing future perspectives in NLPHL.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":" ","pages":"1-8"},"PeriodicalIF":2.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alterations in the RAS pathway underscore the pathogenic complexity of acute myeloid leukemia (AML), yet the full spectrum, including CBL, NF1, PTPN11, KRAS, and NRAS, remains to be fully elucidated. In this retrospective study of 735 adult AML patients, the incidence of RAS pathway alterations was 32.4%, each with distinct clinical characteristics. Venetoclax combined with hypomethylating agents (VEN + HMA) did not significantly improve response rates compared to intensive chemotherapy (IC) group. In the IC group, PTPN11 mutations in the N-SH2 domain showed a trend toward poorer prognosis, though not statistically significant in multivariate analysis, while NRAS mutations correlated with improved outcomes. In the VEN + HMA group, PTPN11 mutations in the N-SH2 domain emerged as an independent adverse prognostic marker. NRAS or KRAS mutations showed no survival advantage compared to wild-type, aligning with their intermediate-risk classification in the 2024 ELN guidelines. These findings emphasize the need for treatment-specific risk stratification for RAS pathway mutations in AML.
{"title":"Molecular, clinical, and prognostic implications of RAS pathway alterations in adult acute myeloid leukemia.","authors":"Fenghong Zhang, Yizi Liu, Yiyan Zhu, Qingyuan Wang, Xiangyu Zhao, Qian Wang, Yu Chen, Suning Chen","doi":"10.1080/10428194.2024.2441855","DOIUrl":"https://doi.org/10.1080/10428194.2024.2441855","url":null,"abstract":"<p><p>Alterations in the RAS pathway underscore the pathogenic complexity of acute myeloid leukemia (AML), yet the full spectrum, including <i>CBL</i>, <i>NF1</i>, <i>PTPN11</i>, <i>KRAS</i>, and <i>NRAS</i>, remains to be fully elucidated. In this retrospective study of 735 adult AML patients, the incidence of RAS pathway alterations was 32.4%, each with distinct clinical characteristics. Venetoclax combined with hypomethylating agents (VEN + HMA) did not significantly improve response rates compared to intensive chemotherapy (IC) group. In the IC group, <i>PTPN11</i> mutations in the N-SH2 domain showed a trend toward poorer prognosis, though not statistically significant in multivariate analysis, while <i>NRAS</i> mutations correlated with improved outcomes. In the VEN + HMA group, <i>PTPN11</i> mutations in the N-SH2 domain emerged as an independent adverse prognostic marker. <i>NRAS</i> or <i>KRAS</i> mutations showed no survival advantage compared to wild-type, aligning with their intermediate-risk classification in the 2024 ELN guidelines. These findings emphasize the need for treatment-specific risk stratification for RAS pathway mutations in AML.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":" ","pages":"1-11"},"PeriodicalIF":2.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-10-22DOI: 10.1080/10428194.2024.2410942
Alejandro Del Rio Verduzco, Ali Al Darobi, Alex Heimbigner, Hayley Heers, Matthew Ulrickson
{"title":"Enasidenib in relapsed aggressive systemic mastocytosis with IDH2 mutation.","authors":"Alejandro Del Rio Verduzco, Ali Al Darobi, Alex Heimbigner, Hayley Heers, Matthew Ulrickson","doi":"10.1080/10428194.2024.2410942","DOIUrl":"10.1080/10428194.2024.2410942","url":null,"abstract":"","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":" ","pages":"170-173"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2025-01-02DOI: 10.1080/10428194.2024.2404247
Arturo Bonometti, Alexandar Tzankov, Ilaria Alborelli, Philip Went, Stefan Dirnhofer
{"title":"CD1a + histiocytoses in primary myelofibrosis patients: just a casual association? A case report and systematic review of the literature.","authors":"Arturo Bonometti, Alexandar Tzankov, Ilaria Alborelli, Philip Went, Stefan Dirnhofer","doi":"10.1080/10428194.2024.2404247","DOIUrl":"https://doi.org/10.1080/10428194.2024.2404247","url":null,"abstract":"","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":"66 1","pages":"139-146"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}