Jessica Allen, Diana Abbott, Joy Eskandar, Steven M Bair, Bradley Haverkos, Jagar Jasem, Manali Kamdar, Ajay Major
{"title":"DA-R-EPOCH May Mitigate the Adverse Prognostic Implication of the Diagnosis-to-Treatment Interval (DTI) in Large B-Cell Lymphomas.","authors":"Jessica Allen, Diana Abbott, Joy Eskandar, Steven M Bair, Bradley Haverkos, Jagar Jasem, Manali Kamdar, Ajay Major","doi":"10.1016/j.clml.2024.09.012","DOIUrl":"https://doi.org/10.1016/j.clml.2024.09.012","url":null,"abstract":"<p><strong>Background: </strong>Short diagnosis-to-treatment interval (DTI) is associated with high-risk disease and poor survival in diffuse large B-cell lymphoma (DLBCL). There is a paucity of literature on DTI and survival in DLBCL treated with first-line DA-R-EPOCH. We hypothesized that rapid initiation of DA-R-EPOCH in aggressive and high-risk DLBCL mitigates the adverse prognostic implication of short DTI.</p><p><strong>Patients and methods: </strong>We retrospectively examined the association of DTI, categorically (short DTI ≤ 14 and long > 14 days) and continuously, with clinical features and survival outcomes in DLBCL treated with first-line DA-R-EPOCH at our institution.</p><p><strong>Results: </strong>A total 190 patients were analyzed, 21% with high-grade DLBCL subtypes, 56% IPI ≥ 3, and median DTI of 13 days. The short DTI cohort contained more patients with IPI ≥ 3, bulky disease, and elevated LDH. When analyzed categorically and continuously, DTI was not associated with significant differences in PFS or OS. There was significant multivariable interaction between bulky disease, DTI, and PFS (P = .033), with improved PFS in patients with bulky disease in the short DTI cohort.</p><p><strong>Conclusion: </strong>We found that negative prognostic implications of DTI are mitigated in DLBCL patients treated with first-line DA-R-EPOCH, suggesting that urgent initiation of DA-R-EPOCH in high-risk DLBCL, including bulky disease, may improve survival. Our study's shorter DTI compared with DTIs reported in prospective DLBCL trials highlights DTI as a marker of external validity in clinical trial results. Future trials should implement protocols encouraging shorter, realistic DTIs to avoid selection bias against high-risk patients who are unable to delay treatment.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459529","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}
Ehab L Atallah, David Wei, Dominick Latremouille-Viau, Carmine Rossi, Andrea Damon, Germano Ferreira, Annie Guérin, Kejal Jadhav
{"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: Real-world asciminib treatment outcomes in CML-CP.","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":"https://doi.org/10.1016/j.clml.2024.09.013","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":null,"pages":null},"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}
{"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":"https://doi.org/10.1016/j.clml.2024.09.009","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":null,"pages":null},"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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrew Lin, Nicole Pearl, Jessica Flynn, Sean Devlin, Parastoo Dahi, Miguel-Angel Perales, Michael Scordo, Gunjan L Shah
{"title":"Influence of Obesity on the Efficacy and Toxicity of Patients Undergoing Autologous Hematopoietic Cell Transplantation for Lymphoma.","authors":"Andrew Lin, Nicole Pearl, Jessica Flynn, Sean Devlin, Parastoo Dahi, Miguel-Angel Perales, Michael Scordo, Gunjan L Shah","doi":"10.1016/j.clml.2024.09.003","DOIUrl":"https://doi.org/10.1016/j.clml.2024.09.003","url":null,"abstract":"<p><p>Hematopoietic cell transplantation requires higher doses of chemotherapy, and practices of adjusting the weight because of concerns of organ toxicity are common. This retrospective analysis of 239 adult recipients of autologous hematopoietic cell transplantation for lymphoma assessed the effect of obesity on transplantation outcomes.</p><p><strong>Background: </strong>Prior data evaluating the impact of obesity in autologous hematopoietic cell transplantation (AHCT) for lymphomas have provided differing results when assessing overall (OS) and progression-free survival (PFS). Impact on survival outcomes have been described, but direct comparison of discrete toxicities is lacking.</p><p><strong>Patients and methods: </strong>We retrospectively compared outcomes with patients divided between 3 groups: nonobese patients (n = 129), obese patients dosed on adjusted body weight (AdjBW) (n = 32), and obese patients dosed on total body weight (TBW) (n = 78).</p><p><strong>Results: </strong>In multivariate analysis of OS with the nonobese group as the comparator, outcomes trended worse in obese patients dosed on AdjBW (HR 1.22, 95% CI 0.52-2.85) but were improved in obese patients dosed on TBW (HR 0.19, 95% CI 0.04-0.85, P = .012). PFS of obese patients dosed on AdjBW vs. the nonobese group was comparable (HR 1.19, 95% CI 0.63-2.24), but improved in obese patients dosed on TBW (HR 0.45, 95% CI 0.23-0.89, P = .021). Notably, no differences were noted between groups in gastrointestinal, infectious, renal, or hepatic toxicities.</p><p><strong>Conclusion: </strong>In summary, our data suggest that recipients of AHCT for lymphoma should be dosed on TBW to maximize curative outcomes with no apparent increase in toxicities.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342794","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}
{"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":null,"pages":null},"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}
Michael Schneider, Sunita D Nasta, Stefan K Barta, Elise A Chong, Jakub Svoboda, Stephen J Schuster, Daniel J Landsburg
{"title":"Analysis of Histologic, Immunohistochemical and Genomic Features of Large B Cell Lymphoma Tumors May Predict Response to Polatuzumab Vedotin Based Therapy in Patients With Relapsed/Refractory Disease.","authors":"Michael Schneider, Sunita D Nasta, Stefan K Barta, Elise A Chong, Jakub Svoboda, Stephen J Schuster, Daniel J Landsburg","doi":"10.1016/j.clml.2024.08.010","DOIUrl":"https://doi.org/10.1016/j.clml.2024.08.010","url":null,"abstract":"<p><strong>Background: </strong>Large B cell lymphoma (LBCL) is the most common form of lymphoma. Polatuzumab vedotin (polatuzumab) is an effective therapy for patients diagnosed with LBCL; however, only limited information regarding pathologic features detected by clinical laboratory assays is available to determine which patients are most likely to benefit from polatuzumab based therapies.</p><p><strong>Patients and methods: </strong>We collected data from real world patients with relapsed or refractory LBCL whose tumors underwent next generation sequencing and were treated with polatuzumab based therapy at a single large academic cancer center. Tumor and patient characteristics were analyzed to look for factors that predict response to polatuzumab based therapies.</p><p><strong>Results: </strong>We identified high grade B cell lymphoma (HGBL) -NOS or MYC/BCL2 histology and presence of MYC rearrangement as factors that predict inferior response to polatuzumab based therapy. Patients with germinal center B cell of origin (GCB COO) LBCL without these factors had a high response rate (73%) to polatuzumab based therapy.</p><p><strong>Conclusion: </strong>In a single center real world retrospective analysis of R/R LBCL patients with available genomic data, polatuzumab based therapy may be less effective in patients with HGBL-NOS or MYC/BCL2 histology and MYC rearrangements, but not in patients with GCB COO LBCL without these features. Routine performance of more comprehensive pathologic analysis of tumors may inform the use of polatuzumab based therapy in patients with LBCL.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364644","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}
{"title":"P-012 Real-World Safety and Early Efficacy of Talquetamab in Patients with Heavily-Pretreated Relapsed/Refractory Multiple Myeloma","authors":"","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":null,"pages":null},"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}
{"title":"P-015 Response of CD8+ T Lymphocytes Under Stimulation of Dendritic Cells Fused With Multiple Myeloma Plasma Cells","authors":"","doi":"10.1016/S2152-2650(24)01918-9","DOIUrl":"10.1016/S2152-2650(24)01918-9","url":null,"abstract":"","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142311864","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}
{"title":"OA-13 Belantamab Mafodotin, Pomalidomide, and Dexamethasone vs Pomalidomide, Bortezomib, and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: Patient-Reported Outcomes from DREAMM-8","authors":"","doi":"10.1016/S2152-2650(24)01854-8","DOIUrl":"10.1016/S2152-2650(24)01854-8","url":null,"abstract":"","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310311","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}