Pub Date : 2024-10-05DOI: 10.1016/j.clml.2024.10.004
Robert W. Gao , Ralph F. Fleuranvil , William S. Harmsen , Randa Tao , Sydney D. Pulsipher , Patricia T. Greipp , Linda B. Baughn , Dragan Jevremovic , Wilson I. Gonsalves , Taxiarchis V. Kourelis , Bradley J. Stish , Jennifer L. Peterson , William G. Rule , Bradford S. Hoppe , William G. Breen , Scott C. Lester
Introduction
We performed a retrospective analysis of patients with multiple myeloma (MM) receiving palliative radiotherapy (RT) and assessed factors associated with local control, with a focus on dose/fractionation and cytogenetics.
Materials and Methods
We included patients who received palliative RT for MM at our institution. Cytogenetics were collected via fluorescence in situ hybridization. Follow-up imaging was used to assess local control.
Results
A total of 239 patients with 362 treated lesions were included. Eighty-six (36.0%) patients had high-risk cytogenetics. Most lesions received 20 Gray (Gy) in 5 fractions (131, 36.2%), 8 Gy in 1 fraction (93, 25.7%), or 30 Gy in 10 fractions (48, 13.3%). At a median follow-up of 4.3 years, 4-year local progression was 13.4% (95% confidence interval [CI]: 10.3-17.5). No cytogenetic abnormalities were correlated with local progression, nor were double- and triple-hit status. There was a nonsignificant trend toward association between number of treated lesions and local progression (HR for >3 vs. 1: 2.43 [95% CI: 0.88-6.74], P = .059). Among patients with >3 treated lesions, equivalent dose in 2 Gy fractions ≥20 Gy reduced progression (HR: 0.05 [95% CI: 0.01-0.23], P = .0001).
Conclusion
In this large study of patients with MM, modern palliative RT achieved excellent rates of long-term local control. Although there was no dose-response observed in the overall cohort, patients with high volume symptomatic disease may benefit from EQD2 ≥20 Gy. High-risk cytogenetics did not appear to influence radioresponsiveness, and standard radiation doses appear to be effective for all MM patients regardless of cytogenetics.
{"title":"Predictors of Local Control With Palliative Radiotherapy for Multiple Myeloma","authors":"Robert W. Gao , Ralph F. Fleuranvil , William S. Harmsen , Randa Tao , Sydney D. Pulsipher , Patricia T. Greipp , Linda B. Baughn , Dragan Jevremovic , Wilson I. Gonsalves , Taxiarchis V. Kourelis , Bradley J. Stish , Jennifer L. Peterson , William G. Rule , Bradford S. Hoppe , William G. Breen , Scott C. Lester","doi":"10.1016/j.clml.2024.10.004","DOIUrl":"10.1016/j.clml.2024.10.004","url":null,"abstract":"<div><h3>Introduction</h3><div>We performed a retrospective analysis of patients with multiple myeloma (MM) receiving palliative radiotherapy (RT) and assessed factors associated with local control, with a focus on dose/fractionation and cytogenetics.</div></div><div><h3>Materials and Methods</h3><div>We included patients who received palliative RT for MM at our institution. Cytogenetics were collected via fluorescence in situ hybridization. Follow-up imaging was used to assess local control.</div></div><div><h3>Results</h3><div>A total of 239 patients with 362 treated lesions were included. Eighty-six (36.0%) patients had high-risk cytogenetics. Most lesions received 20 Gray (Gy) in 5 fractions (131, 36.2%), 8 Gy in 1 fraction (93, 25.7%), or 30 Gy in 10 fractions (48, 13.3%). At a median follow-up of 4.3 years, 4-year local progression was 13.4% (95% confidence interval [CI]: 10.3-17.5). No cytogenetic abnormalities were correlated with local progression, nor were double- and triple-hit status. There was a nonsignificant trend toward association between number of treated lesions and local progression (HR for >3 vs. 1: 2.43 [95% CI: 0.88-6.74], <em>P</em> = .059). Among patients with >3 treated lesions, equivalent dose in 2 Gy fractions ≥20 Gy reduced progression (HR: 0.05 [95% CI: 0.01-0.23], <em>P</em> = .0001).</div></div><div><h3>Conclusion</h3><div>In this large study of patients with MM, modern palliative RT achieved excellent rates of long-term local control. Although there was no dose-response observed in the overall cohort, patients with high volume symptomatic disease may benefit from EQD2 ≥20 Gy. High-risk cytogenetics did not appear to influence radioresponsiveness, and standard radiation doses appear to be effective for all MM patients regardless of cytogenetics.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 3","pages":"Pages 212-218"},"PeriodicalIF":2.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544102","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 : 2024-10-02DOI: 10.1016/j.clml.2024.09.011
Monica Mead , Beth Glenn , Joe Tuscano , Angshuman Saha , Sarah Larson , Sophie Carlson , Jasmine Zain
Background
Prognostic models in peripheral T cell lymphoma (PTCL) have identified biological factors including age, performance status, LDH, and BM involvement as prognostic for survival. The association of social determinants of health (SDH), on PTCL outcomes remains unexplored.
Methods
To evaluate the impact of actionable SDH on PTCL mortality across race groups, we conducted a retrospective cohort study that included all White, Hispanic, Asian/Pacific Islander (PI) and Black adult patients with nodal PTCLs , diagnosed 2000-2020, in California. We utilized Chi2 and Wilcoxon rank-sum tests for descriptive metrics and Kaplan-Meier statistics for mortality estimation. Regression models included patient- (age, sex, race, stage, Charlson Comorbidity Index, histology, treatment, academic center treatment, payer), and neighborhood-level factors (socioeconomic (SES) quintile, proportion without a high school diploma, and rural/urban). Risk factors significant in univariate regression of P < .10 were incorporated into the multivariable model.
Findings
Our analysis included 6158 patients: 51.8% White, 25.8% Hispanic, 14.7% Asians/PI, and 7.6% Black. Hispanics exhibited the longest median survival (33 months) followed by Whites, Blacks, and Asian/PI (25, 20, and 14 months, respectively; P = .011). Risk factors independently associated with inferior lymphoma-specific survival (LSS) included Asian/PI compared with NH Whites (HR, 1.23; 95% CI, 1.10-1.34; P = .0002), AITL/ALCL compared with PTCL, NOS (AITL HR, 1.14; 95% CI, 1.02-1.25; P = .011; ALCL HR, 1.15; 95% CI, 1.04-1.26; P = .004), academic compared to nonacademic facility-type (HR 0.71; 95% CI, 0.64-0.77; P < .01), Medicare compared with uninsured (HR 1.48, 95% CI, 1.25-1.73; P < .01), and the lowest 3 compared to the highest education quartiles (Q2 HR 1.13; 95% CI, 1.01-1.25; P = .021; Q3 HR 1.14; 95% CI, 1.02-1.26; P = .018; Q4 HR 1.22; 95% CI, 1.08-1.36; P < .001). In the least resourced patients, histology, treatment, treatment facility-type, payer and education were independently prognostic for LSS. Academic center treatment was associated with a striking improvement in LSS (academic institution: yes = 101 months, no = 17 months; P < .01).
Interpretation
Treatment facility-type, payer and education, areindependent actionable SDH for PTCL mortality. Treatment center-type had the strongest prognostic association with LSS, conferring a risk reduction of PTCL mortality by nearly 30%.
{"title":"The Impact of Social Determinants of Health on Peripheral T Cell Lymphoma Outcomes: Treatment Center-Type Emerges as a Powerful Prognostic Indicator","authors":"Monica Mead , Beth Glenn , Joe Tuscano , Angshuman Saha , Sarah Larson , Sophie Carlson , Jasmine Zain","doi":"10.1016/j.clml.2024.09.011","DOIUrl":"10.1016/j.clml.2024.09.011","url":null,"abstract":"<div><h3>Background</h3><div>Prognostic models in peripheral T cell lymphoma (PTCL) have identified biological factors including age, performance status, LDH, and BM involvement as prognostic for survival. The association of social determinants of health (SDH), on PTCL outcomes remains unexplored.</div></div><div><h3>Methods</h3><div>To evaluate the impact of actionable SDH on PTCL mortality across race groups, we conducted a retrospective cohort study that included all White, Hispanic, Asian/Pacific Islander (PI) and Black adult patients with nodal PTCLs , diagnosed 2000-2020, in California. We utilized Chi<sup>2</sup> and Wilcoxon rank-sum tests for descriptive metrics and Kaplan-Meier statistics for mortality estimation. Regression models included patient- (age, sex, race, stage, Charlson Comorbidity Index, histology, treatment, academic center treatment, payer), and neighborhood-level factors (socioeconomic (SES) quintile, proportion without a high school diploma, and rural/urban). Risk factors significant in univariate regression of <em>P</em> < .10 were incorporated into the multivariable model.</div></div><div><h3>Findings</h3><div>Our analysis included 6158 patients: 51.8% White, 25.8% Hispanic, 14.7% Asians/PI, and 7.6% Black. Hispanics exhibited the longest median survival (33 months) followed by Whites, Blacks, and Asian/PI (25, 20, and 14 months, respectively; <em>P</em> = .011). Risk factors independently associated with inferior lymphoma-specific survival (LSS) included Asian/PI compared with NH Whites (HR, 1.23; 95% CI, 1.10-1.34; <em>P</em> = .0002), AITL/ALCL compared with PTCL, NOS (AITL HR, 1.14; 95% CI, 1.02-1.25; <em>P</em> = .011; ALCL HR, 1.15; 95% CI, 1.04-1.26; <em>P</em> = .004), academic compared to nonacademic facility-type (HR 0.71; 95% CI, 0.64-0.77; <em>P</em> < .01), Medicare compared with uninsured (HR 1.48, 95% CI, 1.25-1.73; <em>P</em> < .01), and the lowest 3 compared to the highest education quartiles (Q2 HR 1.13; 95% CI, 1.01-1.25; <em>P</em> = .021; Q3 HR 1.14; 95% CI, 1.02-1.26; <em>P</em> = .018; Q4 HR 1.22; 95% CI, 1.08-1.36; <em>P</em> < .001). In the least resourced patients, histology, treatment, treatment facility-type, payer and education were independently prognostic for LSS. Academic center treatment was associated with a striking improvement in LSS (academic institution: yes = 101 months, no = 17 months; <em>P</em> < .01).</div></div><div><h3>Interpretation</h3><div>Treatment facility-type, payer and education, areindependent actionable SDH for PTCL mortality. Treatment center-type had the strongest prognostic association with LSS, conferring a risk reduction of PTCL mortality by nearly 30%.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 3","pages":"Pages 162-177"},"PeriodicalIF":2.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26DOI: 10.1016/j.clml.2024.09.013
Ehab L. Atallah , David Wei , Dominick Latremouille-Viau , Carmine Rossi , Andrea Damon , Germano Ferreira , Annie Guérin , Kejal Jadhav
Background
Tyrosine kinase inhibitors (TKIs) are the mainstay treatment for chronic myeloid leukemia in chronic phase (CML-CP). Asciminib, an ABL/BCR::ABL1 inhibitor which binds to the myristoyl pocket, was recently approved in the US for patients with CML-CP previously treated with ≥2 TKIs or with the T315I mutation. This study described treatment patterns and real-world clinical outcomes among patients with CML-CP treated with asciminib in US clinical practice.
Methods
Electronic health record data from adult patients with CML-CP who initiated asciminib after ≥2 prior TKIs, without the T315I mutation, were obtained from the Flatiron Health database. Time-to-treatment discontinuation and molecular response (MR; time-to-BCR::ABL ≤0.1% and time-to-BCR::ABL1 ≤1%, separately) were evaluated from asciminib initiation (index date) using Kaplan–Meier analyses.
Results
Overall, 97 patients initiated asciminib (median age: 63 years, 50.5% female, 64.9% White) after either 2 (47.4%) or 3 (24.7%), or ≥4 (27.8%) prior TKIs. In total, 85.7% and 78.1% of patients remained on asciminib by 12- and 24-weeks postindex, respectively. Among patients with ≥1 MR assessment postindex, 31.3% (95% confidence interval [CI]: 21.6%, 43.9%) and 49.7% (95% CI: 38.1%, 62.6%) achieved or maintained BCR::ABL1 ≤0.1%, while 51.3% (95% CI: 40.1%, 63.6%) and 64.2% (95% CI: 52.6%, 75.6%) achieved or maintained BCR::ABL1 ≤1%, by 12- and 24-weeks, respectively.
Conclusions
Results of this real-world study describing clinical outcomes among patients with CML-CP treated with asciminib after ≥2 prior TKIs in the US demonstrated that asciminib was well-tolerated and effective. These findings were consistent with results from the ASCEMBL trial.
{"title":"Real-World Evaluation of Treatment Patterns and Clinical Outcomes among Patients With Chronic Myeloid Leukemia in Chronic Phase Treated With Asciminib in Clinical Practice in the United States","authors":"Ehab L. Atallah , David Wei , Dominick Latremouille-Viau , Carmine Rossi , Andrea Damon , Germano Ferreira , Annie Guérin , Kejal Jadhav","doi":"10.1016/j.clml.2024.09.013","DOIUrl":"10.1016/j.clml.2024.09.013","url":null,"abstract":"<div><h3>Background</h3><div>Tyrosine kinase inhibitors (TKIs) are the mainstay treatment for chronic myeloid leukemia in chronic phase (CML-CP). Asciminib, an ABL/BCR::ABL1 inhibitor which binds to the myristoyl pocket, was recently approved in the US for patients with CML-CP previously treated with ≥2 TKIs or with the T315I mutation. This study described treatment patterns and real-world clinical outcomes among patients with CML-CP treated with asciminib in US clinical practice.</div></div><div><h3>Methods</h3><div>Electronic health record data from adult patients with CML-CP who initiated asciminib after ≥2 prior TKIs, without the T315I mutation, were obtained from the Flatiron Health database. Time-to-treatment discontinuation and molecular response (MR; time-to-BCR::ABL ≤0.1% and time-to-BCR::ABL1 ≤1%, separately) were evaluated from asciminib initiation (index date) using Kaplan–Meier analyses.</div></div><div><h3>Results</h3><div>Overall, 97 patients initiated asciminib (median age: 63 years, 50.5% female, 64.9% White) after either 2 (47.4%) or 3 (24.7%), or ≥4 (27.8%) prior TKIs. In total, 85.7% and 78.1% of patients remained on asciminib by 12- and 24-weeks postindex, respectively. Among patients with ≥1 MR assessment postindex, 31.3% (95% confidence interval [CI]: 21.6%, 43.9%) and 49.7% (95% CI: 38.1%, 62.6%) achieved or maintained BCR::ABL1 ≤0.1%, while 51.3% (95% CI: 40.1%, 63.6%) and 64.2% (95% CI: 52.6%, 75.6%) achieved or maintained BCR::ABL1 ≤1%, by 12- and 24-weeks, respectively.</div></div><div><h3>Conclusions</h3><div>Results of this real-world study describing clinical outcomes among patients with CML-CP treated with asciminib after ≥2 prior TKIs in the US demonstrated that asciminib was well-tolerated and effective. These findings were consistent with results from the ASCEMBL trial.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 3","pages":"Pages 178-187.e2"},"PeriodicalIF":2.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459532","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 : 2024-09-23DOI: 10.1016/j.clml.2024.09.009
Despina Fotiou, Meletios A. Dimopoulos
Multiple myeloma is a challenging hematological malignancy, with ongoing efforts toward finding a cure. Dr. Raymond Alexanian has been instrumental in advancing the understanding and treatment of multiple myeloma through his pioneering research. Trained at Dartmouth College and Harvard Medical School, Dr. Alexanian MD Anderson Cancer Center career spanned nearly 5 decades. He developed the highly effective MP (melphalan-prednisone) regimen, which became a standard treatment for years. Dr. Alexanian's exploration of steroids, particularly high-dose dexamethasone, and the collaboration with Dr. Bart Barlogie led to the development of the VAD (vincristine, doxorubicin, and dexamethasone) regimen, significantly improving outcomes for refractory cases. He also contributed to the establishment of high-dose melphalan with autologous stem cell transplantation. Dr. Alexanian's work identified critical prognostic factors and contributed understanding indolent and localized myeloma. His efforts in evaluating new agents, including thalidomide and bortezomib, further enhanced treatment options. Beyond research, his compassionate patient care and advocacy have had a profound impact. Dr. Alexanian's legacy continues to inspire advancements in multiple myeloma treatment, with his innovative approaches reshaping the field and fostering the pursuit of a cure.
{"title":"Dr. Raymond Alexanian: Pioneering Contributions to Multiple Myeloma Research, Treatment, and the Concept of Curability","authors":"Despina Fotiou, Meletios A. Dimopoulos","doi":"10.1016/j.clml.2024.09.009","DOIUrl":"10.1016/j.clml.2024.09.009","url":null,"abstract":"<div><div>Multiple myeloma is a challenging hematological malignancy, with ongoing efforts toward finding a cure. Dr. Raymond Alexanian has been instrumental in advancing the understanding and treatment of multiple myeloma through his pioneering research. Trained at Dartmouth College and Harvard Medical School, Dr. Alexanian MD Anderson Cancer Center career spanned nearly 5 decades. He developed the highly effective MP (melphalan-prednisone) regimen, which became a standard treatment for years. Dr. Alexanian's exploration of steroids, particularly high-dose dexamethasone, and the collaboration with Dr. Bart Barlogie led to the development of the VAD (vincristine, doxorubicin, and dexamethasone) regimen, significantly improving outcomes for refractory cases. He also contributed to the establishment of high-dose melphalan with autologous stem cell transplantation. Dr. Alexanian's work identified critical prognostic factors and contributed understanding indolent and localized myeloma. His efforts in evaluating new agents, including thalidomide and bortezomib, further enhanced treatment options. Beyond research, his compassionate patient care and advocacy have had a profound impact. Dr. Alexanian's legacy continues to inspire advancements in multiple myeloma treatment, with his innovative approaches reshaping the field and fostering the pursuit of a cure.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 3","pages":"Pages 156-161"},"PeriodicalIF":2.7,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-21DOI: 10.1016/j.clml.2024.09.002
Muhammad Ali Khan, Jeanne Palmer
Myelofibrosis (MF) is a rare hematologic malignancy that is characterized by dysregulation of the JAK-STAT pathway resulting in fibrosis of the bone marrow, splenomegaly, and abnormalities in peripheral blood counts including anemia, leukocytosis, and thrombocytopenia. This disease has 2 phenotypic extremes - myeloproliferative and cytopenic. Cytopenic myelofibrosis presents with pronounced cytopenia and a different landscape of genetic mutations which results in worse clinical outcomes and a poor prognosis. Patients with cytopenic MF are at high risk of developing various complications like bleeding, infections, and transfusion dependency. Historically, the only Federal Drug Administration (FDA) approved therapy was ruxolitinib, a JAK1/2 inhibitor, which improved constitutional symptoms and splenomegaly, however, exacerbated anemia and thrombocytopenia.1,2 There were very few options for patients with anemia and thrombocytopenia, and supportive treatments for these problems lack efficacy. Fortunately, there are newer treatment options which may allow for treatment of the symptoms and splenomegaly in the setting of cytopenias and even improve cytopenias. This up-to-date review not only highlights the prevalent options in therapeutic marketplace, but also sheds light on the significant unmet need of addressing anemia and thrombocytopenia in cytopenic MF.
{"title":"SOHO State of the Art Updates and Next Questions | Updates on Myelofibrosis With Cytopenia.","authors":"Muhammad Ali Khan, Jeanne Palmer","doi":"10.1016/j.clml.2024.09.002","DOIUrl":"https://doi.org/10.1016/j.clml.2024.09.002","url":null,"abstract":"<p><p>Myelofibrosis (MF) is a rare hematologic malignancy that is characterized by dysregulation of the JAK-STAT pathway resulting in fibrosis of the bone marrow, splenomegaly, and abnormalities in peripheral blood counts including anemia, leukocytosis, and thrombocytopenia. This disease has 2 phenotypic extremes - myeloproliferative and cytopenic. Cytopenic myelofibrosis presents with pronounced cytopenia and a different landscape of genetic mutations which results in worse clinical outcomes and a poor prognosis. Patients with cytopenic MF are at high risk of developing various complications like bleeding, infections, and transfusion dependency. Historically, the only Federal Drug Administration (FDA) approved therapy was ruxolitinib, a JAK1/2 inhibitor, which improved constitutional symptoms and splenomegaly, however, exacerbated anemia and thrombocytopenia.<sup>1</sup><sup>,</sup><sup>2</sup> There were very few options for patients with anemia and thrombocytopenia, and supportive treatments for these problems lack efficacy. Fortunately, there are newer treatment options which may allow for treatment of the symptoms and splenomegaly in the setting of cytopenias and even improve cytopenias. This up-to-date review not only highlights the prevalent options in therapeutic marketplace, but also sheds light on the significant unmet need of addressing anemia and thrombocytopenia in cytopenic MF.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616056","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 : 2024-09-12DOI: 10.1016/j.clml.2024.09.001
Michael J Hochman, Colin A Vale, Anthony M Hunter
Myelofibrosis (MF) is a chronic myeloid neoplasm characterized by myeloproliferation, bone marrow fibrosis, splenomegaly, and constitutional symptoms related to pro-inflammatory cytokine signaling. Biologically, MF is characterized by constitutive activation of JAK-STAT signaling; accordingly, JAK inhibitors have been rationally developed to treat MF. Following the initial approval of ruxolitinib in 2011, three additional agents have been approved: fedratinib, pacritinib, and momelotinib. As these therapies are noncurative, allogeneic stem cell transplantation remains a key treatment modality and patients with MF who are deemed candidates should be referred to a transplant center. This potentially curative but toxic approach is typically reserved for patients with higher-risk disease, and JAK inhibitors are recommended in the pretransplant setting. JAK inhibitors have proven effective at managing splenomegaly and constitutional symptoms and should be started early in the disease course in patients presenting with these clinical manifestations; asymptomatic patients may initially be followed with close surveillance. Drug-related myelosuppression has been a challenge with initial JAK inhibitors, particularly in patients presenting with a cytopenic phenotype. However, newer agents, namely pacritinib and momelotinib, have proven more effective in this setting and are approved for patients with significant thrombocytopenia and anemia, respectively. Resistance or disease progression is clinically challenging and may be defined by several possible events, such as increasing splenomegaly or progression to accelerated or blast phase disease. However, with multiple JAK inhibitors now approved, sequencing of these agents appears poised to improve outcomes. Additionally, novel JAK inhibitors and JAK inhibitor-based combinations are in clinical development.
骨髓纤维化（MF）是一种慢性骨髓肿瘤，其特征是骨髓增生、骨髓纤维化、脾脏肿大以及与促炎细胞因子信号有关的体征。从生物学角度看，骨髓增生性疾病的特征是 JAK-STAT 信号的构成性激活；因此，人们合理地开发了 JAK 抑制剂来治疗骨髓增生性疾病。继 2011 年首次批准鲁索利替尼之后，又有三种药物获得批准：非瑞替尼、帕克替尼和莫美罗替尼。由于这些疗法都是非根治性的，异基因干细胞移植仍然是一种重要的治疗方式，被认为是候选者的MF患者应被转介到移植中心。这种可能治愈但有毒性的方法通常只用于风险较高的患者，建议在移植前使用JAK抑制剂。事实证明，JAK抑制剂可有效控制脾肿大和体征，对于出现这些临床表现的患者，应在病程早期开始使用；无症状的患者最初可进行密切监测。与药物相关的骨髓抑制一直是最初的 JAK 抑制剂所面临的挑战，尤其是在出现细胞减少表型的患者中。然而，较新的药物，即帕克替尼（pacritinib）和莫美罗替尼（momelotinib），已被证明在这种情况下更为有效，并已获准分别用于有明显血小板减少和贫血的患者。耐药或疾病进展在临床上具有挑战性，可由几种可能发生的情况来定义，如脾脏肿大或进展为加速期或爆发期疾病。不过，随着多种 JAK 抑制剂的获批，对这些药物进行排序似乎有望改善治疗效果。此外，新型 JAK 抑制剂和基于 JAK 抑制剂的联合用药也在临床开发中。
{"title":"SOHO State of the Art Updates and Next Questions | Choosing and Properly Using a JAK Inhibitor in Myelofibrosis.","authors":"Michael J Hochman, Colin A Vale, Anthony M Hunter","doi":"10.1016/j.clml.2024.09.001","DOIUrl":"https://doi.org/10.1016/j.clml.2024.09.001","url":null,"abstract":"<p><p>Myelofibrosis (MF) is a chronic myeloid neoplasm characterized by myeloproliferation, bone marrow fibrosis, splenomegaly, and constitutional symptoms related to pro-inflammatory cytokine signaling. Biologically, MF is characterized by constitutive activation of JAK-STAT signaling; accordingly, JAK inhibitors have been rationally developed to treat MF. Following the initial approval of ruxolitinib in 2011, three additional agents have been approved: fedratinib, pacritinib, and momelotinib. As these therapies are noncurative, allogeneic stem cell transplantation remains a key treatment modality and patients with MF who are deemed candidates should be referred to a transplant center. This potentially curative but toxic approach is typically reserved for patients with higher-risk disease, and JAK inhibitors are recommended in the pretransplant setting. JAK inhibitors have proven effective at managing splenomegaly and constitutional symptoms and should be started early in the disease course in patients presenting with these clinical manifestations; asymptomatic patients may initially be followed with close surveillance. Drug-related myelosuppression has been a challenge with initial JAK inhibitors, particularly in patients presenting with a cytopenic phenotype. However, newer agents, namely pacritinib and momelotinib, have proven more effective in this setting and are approved for patients with significant thrombocytopenia and anemia, respectively. Resistance or disease progression is clinically challenging and may be defined by several possible events, such as increasing splenomegaly or progression to accelerated or blast phase disease. However, with multiple JAK inhibitors now approved, sequencing of these agents appears poised to improve outcomes. Additionally, novel JAK inhibitors and JAK inhibitor-based combinations are in clinical development.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364645","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 : 2024-09-01DOI: 10.1016/S2152-2650(24)01915-3
Bruno Costa, Carlyn Tan, Tala Shekarkhand, Ross Firestone, Eric Jurgens, Kevin Miller, Alexander Lesokhin, Gunjan Shah, Neha Korde, Sridevi Rajeeve, David Chung, Heather Landau, Michael Scordo, Hani Hassoun, Kylee Maclachlan, Urvi Shah, Malin Hultcrantz, Issam Hamadeh, Sergio Giralt, Sham Mailankody, Hamza Hashmi
{"title":"P-012 Real-World Safety and Early Efficacy of Talquetamab in Patients with Heavily-Pretreated Relapsed/Refractory Multiple Myeloma","authors":"Bruno Costa, Carlyn Tan, Tala Shekarkhand, Ross Firestone, Eric Jurgens, Kevin Miller, Alexander Lesokhin, Gunjan Shah, Neha Korde, Sridevi Rajeeve, David Chung, Heather Landau, Michael Scordo, Hani Hassoun, Kylee Maclachlan, Urvi Shah, Malin Hultcrantz, Issam Hamadeh, Sergio Giralt, Sham Mailankody, Hamza Hashmi","doi":"10.1016/S2152-2650(24)01915-3","DOIUrl":"10.1016/S2152-2650(24)01915-3","url":null,"abstract":"","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"24 ","pages":"Pages S46-S47"},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310727","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 : 2024-09-01DOI: 10.1016/S2152-2650(24)01900-1
Christopher Parrish, Alexandra Welsh, John Ashcroft, Catherine Olivier, Anna Hockaday, Jamie Cavenagh, John Snowden, Mark Drayson, Ruth De Tute, Roger Owen, Kwee Yong, Mamta Garg, Kevin Boyd, Hamdi Sati, Sharon Gillson, Jeanine Richards, Mark Cook, Lesley Roberts, David Cairns, Gordon Cook
Pub Date : 2024-09-01DOI: 10.1016/S2152-2650(24)01853-6
Andrew Spencer, Marc-Steffen Raab, Shinsuke Iida, María-Victoria Mateos Manteca, Michele Cavo, Paula Rodriguez-Otero, P. Joy Ho, Yunxin Chen, Paul Ferguson, Irit Avivi, Paolo Corradini, Esther Chan, Andy Chen, Bertrand Arnulf, Udo Holtick, Adam Sperling, Jufen Chu, David Pearson, Davide Germano, Ronan Feighery, Nikhil Munshi
{"title":"OA-12 Interim Phase 2 Study Results of Durcabtagene Autoleucel (PHE885), a T-Charge™ Manufactured BCMA-Directed CAR-T Cell Therapy in Patients (pts) with r/r Multiple Myeloma (RRMM)","authors":"Andrew Spencer, Marc-Steffen Raab, Shinsuke Iida, María-Victoria Mateos Manteca, Michele Cavo, Paula Rodriguez-Otero, P. Joy Ho, Yunxin Chen, Paul Ferguson, Irit Avivi, Paolo Corradini, Esther Chan, Andy Chen, Bertrand Arnulf, Udo Holtick, Adam Sperling, Jufen Chu, David Pearson, Davide Germano, Ronan Feighery, Nikhil Munshi","doi":"10.1016/S2152-2650(24)01853-6","DOIUrl":"10.1016/S2152-2650(24)01853-6","url":null,"abstract":"","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"24 ","pages":"Pages S8-S9"},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310310","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}
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