Clinical Lymphoma, Myeloma & Leukemia最新文献

{"title":"A Real-World Evaluation of Frontline Treatment for Acute Myeloid Leukemia With Azacitidine Plus Venetoclax.","authors":"Joseph Brandwein, David Page, Elena Liew, Mark Hnatiuk, Lauren Bolster, Marlene Hamilton, Daniel Sawler, Peng Wang","doi":"10.1016/j.clml.2025.01.024","DOIUrl":"https://doi.org/10.1016/j.clml.2025.01.024","url":null,"abstract":"<p><strong>Background: </strong>The combination of venetoclax + azacitidine (VenAza) has become the standard frontline treatment for older unfit AML patients.</p><p><strong>Methods: </strong>We analyzed outcomes using VenAza for previously untreated unfit AML patients at a single center between 2020-2024.</p><p><strong>Results: </strong>The overall response rate (ORR) was 69/105 (66%), was highest for patients with NPM1 (78%) and IDH1/2 (82%) mutations and lowest with TP53 mutations (40%). The median overall survival (OS) was 9.6 months, and 16.3 months for those achieving CR/CRi. There was no significant difference in OS between those achieving CR and CRi (p = 0.077). Patients treated between 2022-24 had a lower early death rate (8% vs. 22%) and better OS (median 10.4 vs 5.8 mos, p = 0.033) than those treated between 2020-21. There was no difference in OS between by age grouping or for patients with prior hypomethylating agent exposure. Patients with FLT3-ITD/RAS or TP53 mutations had an inferior OS compared with the other patients (median OS 8.1, 1.7 and 16 months, respectively). On multivariate analysis, achievement of CR/CRi was associated with better OS (p < 0.001), and FLT3-ITS/RAS/TP53 mutations were associated with inferior OS (p = 0.003), while ELN2022 risk group was not associated with OS. The median DFS for patients achieving CR/CRi was 7.1, 4.9 and 21 mos, for those with FLT3-ITD/RAS, TP53 and others, respectively (p = 0.003).</p><p><strong>Conclusions: </strong>This real-world analysis confirmed the prognostic importance of the mutational risk classification with VenAza treatment. OS was inferior to that reported in the VIALE A study but did improve over time.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536701","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":"Enhancing Multiple Myeloma Care: Implementation of Pharmacist-Led Prescribing of Immunomodulatory Drugs in an Academic Medical Setting.","authors":"Amy Indorf, Mary Kwok, Mark Jao, Ashley Chen, Grace T Baek, Rahul Banerjee, Kara I Cicero, Andrew J Cowan, Andrew J Portuguese, Linda Yoon, Eve M Segal","doi":"10.1016/j.clml.2025.01.013","DOIUrl":"https://doi.org/10.1016/j.clml.2025.01.013","url":null,"abstract":"<p><strong>Background: </strong>The oncology healthcare landscape has transformed and has demonstrated the need for efficient care delivery models due to improved survival resulting in larger patient panels. Pharmacists can prescribe oral anticancer agents (OAA), laboratory orders, and supportive care treatments as licensed independent practitioners (LIP) under their pharmacist license. Using immunomodulators (IMiDs) for patients with multiple myeloma (MM) has complexities with regulatory requirements for prescribing. At our institution, the care team was spending about 240 hours per month satisfying regulatory activities. We aim to characterize the effectiveness of pharmacist LIPs for patients with MM receiving IMiD treatment.</p><p><strong>Methods: </strong>A multidisciplinary quality improvement team implemented a model for OAA management with pharmacist LIPs. Patients were evaluated for IMiD adherence. Medication possession ratios (MPR) were collected using fill history for patients with 6 months of fill history pre and postpharmacist LIPs involvement, and paired McNemar's Test assessed differences in adherence. A care team survey gauged satisfaction.</p><p><strong>Results: </strong>The pharmacist patient panel comprised 246 patients. There were similar adherence rates, with an MPR of 96% preintervention and 96.55% postintervention. All survey participants recommended the pharmacist prescriber for IMiDs and reported positive reviews of pharmacist involvement.</p><p><strong>Conclusion: </strong>Management of OAAs by pharmacist LIPs is viable clinical model. The care team reduced their administrative burden while empowering pharmacists to practice at the top of their license. This framework serves as a guide for institutions to adapt and optimize OAA management in an increasingly complex therapeutic landscape.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522695","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":"Role of Pulmonary Function Tests to Predict Complications After Chimeric Antigen Receptor T-Cell Therapy.","authors":"Jeremy Walder, Felipe Soto-Lanza, Lei Feng, Sairah Ahmed, Sattva Neelapu, Amy Ayers, Horiana B Grosu, Saadia A Faiz, Loretta Nastoupil, Ajay Sheshadri","doi":"10.1016/j.clml.2025.01.019","DOIUrl":"https://doi.org/10.1016/j.clml.2025.01.019","url":null,"abstract":"<p><strong>Background: </strong>Chimeric antigen receptor T-cell therapy (CAR-T) has transformed the treatment of certain hematologic malignancies, but toxicities limit efficacy. The role of pre-CAR-T pulmonary function testing (PFT) to predict toxicities is unclear.</p><p><strong>Objective: </strong>Our aim was to examine the association between PFTs obtained prior to CAR-T and subsequent complications in patients with lymphoma.</p><p><strong>Study design: </strong>We conducted a retrospective study of patients who underwent standard-of-care CAR-T at our institution with pretherapy PFTs. Race-neutral normative equations from the Global Lung Initiative were used to generate percent-predicted values (PPV) for spirometry and diffusing capacity of the lungs for carbon monoxide (DLCO). Lung function score (LFS) was calculated by combining the forced expiratory volume in the first second (FEV₁) and the diffusion capacity of the lung for carbon monoxide corrected for hemoglobin level (cDLCO) in an equally distributed manner, with higher score denoting worse lung function. Binary logistic regression models were used to compare the association of PFTs with complications after CAR-T. Cox regression models were additionally fit to identify predictors of mortality.</p><p><strong>Results: </strong>Of 218 individuals who underwent CAR-T therapy, 66 had PFTs performed within 12 months prior to lymphodepletion. Higher LFS was associated with higher risk of CRS (OR 4.3, 95% CI, 1.4-29, P = .048), after adjusting for lines of treatment. When adjusting for lines of treatment, both FEV₁ (OR = 0.96, 95% CI, 0.93-0.99, P = .05) and FVC (OR = 0.96, 95% CI 0.92-0.99, P = .03) are protective for ICANS. PFT abnormalities were not associated with early or late mortality.</p><p><strong>Conclusion: </strong>The combination of pre-CAR-T spirometry and cDLCO may help clinicians understand the risk for toxicities after CAR-T cell therapy.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499439","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":"Follicular Lymphoma: Paving the Path to Cures Through Philanthropy.","authors":"Mitchell R Smith, Michel Azoulay, Lee M Greenberger","doi":"10.1016/j.clml.2025.01.020","DOIUrl":"https://doi.org/10.1016/j.clml.2025.01.020","url":null,"abstract":"","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457101","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 | Novel Immunotherapy Combinations for the Treatment of Indolent B-Cell Lymphoma.","authors":"Tony Z Zhuang, Chen Zhang, Paolo Strati","doi":"10.1016/j.clml.2025.01.021","DOIUrl":"https://doi.org/10.1016/j.clml.2025.01.021","url":null,"abstract":"<p><p>Chemoimmunotherapy (CIT) is the standard frontline treatment for advanced indolent non-Hodgkin lymphomas (iNHL). While lenalidomide-based immunotherapy remains the standard of care for relapsed iNHL, its frontline use is limited, due to nonsuperiority as compared to CIT. Agents that engage T-cells, polarize macrophage phenotype to a more antitumoral phenotype, and/or to target epigenetic pathways could enhance immunotherapy. We summarize in this review safety plus efficacy data from published and/or ongoing clinical trials investigating the combination of lenalidomide-based immunotherapy with T-cell engagers (including anti-CD3/CD20 bispecific antibodies), macrophage-targeting agents (including BTK inhibitors and anti-CD47 antibodies), and epigenetic modifiers (including EZH2 inhibitors). We also summarize the activity in iNHL of agents targeting antigens other than CD20 (including CD19 and CD79b), and novel immunotherapies and cellular therapies (including NK-cell based treatments). The therapeutic landscape of iNHL is soon to significantly change.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514876","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":"A First-in-Human Phase I Study of LOXO-338, an Oral Selective Bcl-2 Inhibitor, in Patients With Advanced Hematologic Malignancies.","authors":"Michal Kwiatek, Guru Subramanian Guru Murthy, Marc Hoffmann, Benoit Tessoulin, Alexey Danilov, Alvaro J Alencar, Nirav N Shah, Hervé Ghesquieres, Steven Le Gouill, Wojciech Jurczak, Hongmei Han, Eunice Yuen, Vishalkumar Patel, Yingying Guo-Avrutin, James M Pauff, Lindsey E Roeker","doi":"10.1016/j.clml.2025.01.018","DOIUrl":"https://doi.org/10.1016/j.clml.2025.01.018","url":null,"abstract":"<p><strong>Background: </strong>LOXO-338 is a novel, orally bioavailable small-molecule inhibitor of Bcl-2, designed to achieve selectivity for Bcl-2 over Bcl-xL, thus avoiding dose-limiting thrombocytopenia associated with Bcl-xL inhibition. This first-in-human, open-label, Phase 1 study investigated LOXO-338 in patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or B-cell non-Hodgkin lymphoma (NHL) (NCT05024045).</p><p><strong>Patients and methods: </strong>Patients with histologically confirmed advanced B-cell malignancies who had received ≥ 2 prior therapies were enrolled in Phase 1 dose escalation (interval 3 + 3 design). LOXO-338 was administered orally as 50 to 300 mg once-daily dose until discontinuation due to progressive disease or unacceptable toxicity. The primary objective was to determine the maximum tolerated dose (MTD)/recommended Phase 2 dose of LOXO-338. Secondary objectives included safety, tolerability, pharmacokinetics, and preliminary antitumor activity.</p><p><strong>Results: </strong>In total, 27 patients with CLL/SLL (n = 10) or NHL (n = 17) were treated. No dose-limiting toxicities occurred and the MTD was not reached. Treatment-emergent adverse events occurred in 23 patients (85%); anemia (22%) and fatigue (22%) were the most prevalent. Treatment-related adverse events (TRAEs) occurred in 15% and were mostly grade 1 (11%) or 2 (4%); grade ≥ 3 or serious TRAEs were not reported. Tumor lysis syndrome was not observed. The overall response rate was 19% (95% CI: 6.3, 38.1) and disease control rate was 67% (95% CI: 46, 83.5). LOXO-338 was orally bioavailable with dose-dependent increases in exposure.</p><p><strong>Conclusion: </strong>LOXO-338 was well tolerated with a favorable safety profile in previously treated patients with advanced hematologic malignancies. Preliminary efficacy was observed in this heavily pretreated population supporting further investigation.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499406","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":"Real-World Safety and Tolerability of Rapid, 30-Minutes, Intravenous Isatuximab in Patients With Multiple Myeloma.","authors":"Rami Kotb, Marc Geirnaert, Emily Rimmer, Vi Dao, Jayne Kasian, Leonard Minuk, Ivan Landego","doi":"10.1016/j.clml.2025.01.022","DOIUrl":"https://doi.org/10.1016/j.clml.2025.01.022","url":null,"abstract":"<p><strong>Background: </strong>Isatuximab-based combinations are widely used to treat patients with relapsed or refractory multiple myeloma, and will soon become part of the standard first-line therapies in transplant-eligible and transplant-ineligible newly diagnosed patients. Isatuximab is currently approved for intravenous fixed volume (250ml) administration, with a maximum infusion rate of 200 ml/h and at least 75 minutes required for 1 administration. A recent clinical trial suggested the safety of a faster, 30-minute administration of isatuximab. Other trials are ongoing. Based on this early data as well as previous experience with monoclonal antibody therapies, the rapid, 30-minutes intravenous isatuximab administration was adopted at our institution as standard of care.</p><p><strong>Methodology: </strong>We here report the early real-world data on this new standard.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499359","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":"The Prospective Use of Avapritinib in Relapsed/Refractory (R/R) RUNX1-RUNX1T1-Positive AML Patients With KIT Mutation.","authors":"Si-Yi Han, Xiao-Yan Xu, Meng Zhou, Jin-Wen Su, Hai-Xia Zhou, Yue Han","doi":"10.1016/j.clml.2025.01.007","DOIUrl":"https://doi.org/10.1016/j.clml.2025.01.007","url":null,"abstract":"","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457103","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":"Is t(11;14) Always a Standard-Risk Cytogenetic Abnormality? Results From GEM05MENOS65 and GEM2012 PETHEMA/GEM Transplantation Trials.","authors":"David F Moreno, Albert Oriol, Javier de la Rubia, Miguel T Hernández, María Belén Iñigo, Luis Palomera, Felipe de Arriba, Yolanda González, Ana Isabel Teruel, Jordi López Pardo, Ana López de la Guía, Antonia Sampol, Rafael Ríos-Tamayo, Anna Sureda, Norma C Gutiérrez, Maria-Jose Calasanz, María Luisa Martín Ramos, María Victoria Mateos, Jesús San Miguel, Juan José Lahuerta, Joan Bladé, Laura Rosiñol","doi":"10.1016/j.clml.2025.01.014","DOIUrl":"https://doi.org/10.1016/j.clml.2025.01.014","url":null,"abstract":"<p><strong>Purpose: </strong>Recent studies describe inferior outcomes in newly diagnosed multiple myeloma (NDMM) patients with t(11;14) treated with novel agents.</p><p><strong>Materials and methods: </strong>We analyzed 240 NDMM transplant eligible (TE) patients who received triplet induction regimen in the GEM05MENOS65 (bortezomib, thalidomide and dexamethasone - VTD) and GEM2012 (bortezomib, lenalidomide and dexamethasone - VRD) clinical trials.</p><p><strong>Results: </strong>t(11;14) and standard risk (SR) non-t(11;14) were prevalent in 51 (21%) and 189 (79%) patients, respectively. Patients with t(11;14) treated with VTD had a lower overall response rate (ORR) (84% vs. 97%, P = .044) and lower negative minimal residual disease (MRD) (7.7% vs 35.1%, P = .049) after induction, as compared to SR non-t(11;14), while there were no differences in ORR (87% vs. 89%) or negative MRD (13.2% vs. 24.4%, P = .2) for these 2 subgroups in patients treated with VRD. The presence of t(11;14) impacted negatively on PFS in patients with VTD (hazard ratio 2.70; P = .005), while no differences were observed in those treated with VRD.</p><p><strong>Conclusion: </strong>TE NDMM patients harboring t(11;14) had an inferior outcome compared with SR patients when receiving induction therapy with VTD while no differences were observed when receiving a lenalidomide containing regimen.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425106","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":"Characteristics and Survival of Secondary Acute Myeloid Leukemia From Myelodysplastic Syndromes in Older Adults: A Population Analysis.","authors":"Akshee Batra, Andrew Sparks, Rohit Singh, Neil A Zakai, Diego Adrianzen Herrera","doi":"10.1016/j.clml.2025.01.012","DOIUrl":"https://doi.org/10.1016/j.clml.2025.01.012","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) arising from myelodysplastic syndromes (MDS) is a unique subtype of secondary AML (sAML) with poor prognosis. We defined its epidemiologic profile in older adults.</p><p><strong>Methods: </strong>Using the SEER-Medicare database, we identified MDS cases that progressed to AML between 2007 and 2017, during the era of hypomethylating agents (HMA). Established algorithms determined demographics, MDS histology, MDS risk by Simplified Myelodysplastic Syndrome Risk Score (SMMRS), comorbidity, transfusion burden, and HMA therapy. We defined overall survival (OS) after sAML, and examined factors associated with AML and mortality, including the impact of prior HMA therapy.</p><p><strong>Results: </strong>Of 15,227 MDS patients, 12.3% developed AML. Incidence varied by MDS histology and SMMRS. Time to AML was shorter with higher SMMRS. Older age and higher comorbidity were associated with lower odds of AML. Higher SMMRS (OR = 2.5, 95CI: 2.0-3.0), transfusion dependence (OR = 2.6, 95CI: 2.1-3.2), and HMA use (OR = 4.9, 95CI: 4.4-5.5) were associated with increased transformation risk. Median OS after AML diagnosis was 3 months. OS rates at 1 and 2 years were 25% and 12%. Survival varied by antecedent MDS histology, being longest in those with ringed sideroblasts (P < .001). Older age (HR = 1.4, 95CI: 1.1-1.9) and higher SMMRS (HR = 1.8, 95CI: 1.5-2.2) were associated with risk of death. Antecedent HMA exposure was associated with longer OS (4 vs. 2 months, P < .01), with 4 or more HMA cycles associated with decreased risk of death (HR = 0.53, 95CI: 0.47-0.60).</p><p><strong>Conclusion: </strong>Risk of sAML is significant even in lower-risk MDS histologies. Survival is poor and varies by antecedent MDS characteristics. HMA exposure association with longer survival warrants further analysis.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425104","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}