Clinical Lymphoma, Myeloma & Leukemia最新文献

{"title":"Clinical Characteristics and Survival Outcomes of Patients With Primary and Secondary Plasma Cell Leukemia According to the 2021 Definition: A Single Center Retrospective Study","authors":"Khalid Shalaby ,&nbsp;Farhan Azad ,&nbsp;Sarah Parker ,&nbsp;Chong Wang ,&nbsp;Han Yu ,&nbsp;Kristopher Attwood ,&nbsp;Jens Hillengass","doi":"10.1016/j.clml.2024.10.014","DOIUrl":"10.1016/j.clml.2024.10.014","url":null,"abstract":"<div><h3>Introduction</h3><div>Plasma cell leukemia (PCL) is a rare malignancy with poor overall survival (OS). Recently, its diagnostic criteria were revised by lowering the threshold of circulating plasma cells from ≥ 20% to ≥ 5%.</div></div><div><h3>Methods</h3><div>Between 2010 and 2024, patients with primary PCL (pPCL) and secondary PCL (sPCL) were identified at a tertiary center. We retrospectively analyzed baseline characteristics, treatment, and survival in months (m).</div></div><div><h3>Results</h3><div>We identified 30 patients with pPCL and 29 patients with sPCL. The median time to sPCL in patients who received Daratumumab (Dara)-containing regimens for multiple myeloma was 46.8m compared with 12.3m in patients who did not (P=0.007). Of the whole cohort, 51.9% received an induction regimen with novel agents without chemotherapy. Of the evaluable patients with pPCL and sPCL, 82.1% (23/28) and 64.7% (11/17) achieved partial response or better respectively. Median progression free survival was significantly worse in patients with sPCL than pPCL (2.2 vs. 38.3 months; HR 0.16; 95% CI (0.07-0.35), <em>P</em> &lt; .001). Median OS was also worse in patients with sPCL compared with pPCL (3.1 months vs. NR [not reached]; HR 0.09; 95%CI 0.04-0.23, <em>P</em> &lt; .001). The median post-SCT survival for patients with pPCL was NR compared with 6.7m for patients with sPCL (HR 0.17; 95% CI (0.03-0.83), <em>P</em> = .03). Dara-refractory status was associated with worse OS (HR 5.63; 95% CI (2.75-11.51), <em>P</em> &lt; .0001).</div></div><div><h3>Conclusion</h3><div>Outcomes of pPCL are improving but remain dismal for sPCL. We explored the role of novel agents, especially Dara, in the treatment of PCL. More prospective trials are needed to improve its outcomes.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 1","pages":"Pages 67-75"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692479","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":"DA-R-EPOCH May Mitigate the Adverse Prognostic Implication of the Diagnosis-to-Treatment Interval (DTI) in Large B-Cell Lymphomas","authors":"Jessica Allen ,&nbsp;Diana Abbott ,&nbsp;Joy Eskandar ,&nbsp;Steven M. Bair ,&nbsp;Bradley Haverkos ,&nbsp;Jagar Jasem ,&nbsp;Manali Kamdar ,&nbsp;Ajay Major","doi":"10.1016/j.clml.2024.09.012","DOIUrl":"10.1016/j.clml.2024.09.012","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Patients and Methods</h3><div>We retrospectively examined the association of DTI, categorically (short DTI ≤ 14 and long &gt; 14 days) and continuously, with clinical features and survival outcomes in DLBCL treated with first-line DA-R-EPOCH at our institution.</div></div><div><h3>Results</h3><div>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 (<em>P</em> = .033), with improved PFS in patients with bulky disease in the short DTI cohort.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 1","pages":"Pages e26-e33"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","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}

{"title":"Efficacy and Safety of the First-in-Class STAMP-Inhibitor Asciminib in Patients With Chronic Myeloid Leukemia","authors":"Hiroshi Ureshino ,&nbsp;Shinya Kimura","doi":"10.1016/j.clml.2024.10.010","DOIUrl":"10.1016/j.clml.2024.10.010","url":null,"abstract":"<div><div>The survival outcomes of patients with chronic myeloid leukemia (CML) have significantly improved due to the introduction of adenosine triphosphate (ATP) -competitive ABL1 tyrosine kinase inhibitors (TKIs). However, several patients with CML eventually develop treatment resistance or intolerance during the course of ATP-competitive ABL1 TKI treatment. ABL1 TKIs inhibit other tyrosine kinases via their off-target effects. This mechanism leads to the development of adverse events, which may result in treatment discontinuation. Asciminib is a first-in-class STAMP (specifically targeting the ABL myristoyl pocket) inhibitor used in patients with chronic-phase CML who exhibit resistance or intolerance to two prior TKI therapies. Asciminib was found to have excellent efficacy and safety therapeutic profiles. The lack of comprehensive reviews about asciminib, thus, the current study aimed to evaluate the clinical and preclinical evidence of the efficacy and safety of asciminib.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 1","pages":"Pages e57-e61"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603550","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 Real-World Analysis on Access to Triplet and Quadruplet Therapy in Newly Diagnosed Multiple Myeloma Patients in the United States","authors":"Ludovic Saba ,&nbsp;Chieh-Lin Fu ,&nbsp;Hong Liang ,&nbsp;Chakra P. Chaulagain","doi":"10.1016/j.clml.2024.10.006","DOIUrl":"10.1016/j.clml.2024.10.006","url":null,"abstract":"<div><h3>Background</h3><div>Disparities in access to triplet and quadruplet therapy for multiple myeloma (MM) patients remain a challenge in the United States. We aimed to investigate demographic and socioeconomic factors influencing treatment access using NCDB data.</div></div><div><h3>Patients and Methods</h3><div>We analyzed 101,867 MM patients diagnosed between 2004 and 2020. Multinomial logistic regression and multivariable cox regression were employed to assess factors influencing treatment access and survival, respectively.</div></div><div><h3>Results</h3><div>Black patients exhibited significantly lower odds of receiving triplet and quadruplet therapy compared to White patients. Socioeconomic factors such as insurance status and household income also influenced treatment access. However, Black and Hispanic patients demonstrated better survival outcomes despite disparities in access.</div></div><div><h3>Conclusion</h3><div>Racial, socioeconomic, and insurance-related disparities persist in access to optimal MM therapy in the USA. Addressing these barriers is essential for ensuring equitable healthcare delivery and improving patient outcomes.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 1","pages":"Pages e1-e10"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615967","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":"Estimated Financial Savings From Clinical Studies at Oslo Myeloma Center in the Period 2015-2021","authors":"Lars Henrik Dahl Hamnvik ,&nbsp;Stella Eide-Olsen ,&nbsp;Arne Fosseng ,&nbsp;Fredrik Hellem Schjesvold","doi":"10.1016/j.clml.2024.07.015","DOIUrl":"10.1016/j.clml.2024.07.015","url":null,"abstract":"<div><h3>Background</h3><div>The number of clinical studies in the Western world has been declining the last decade. Clinical studies offer valuable opportunities for cancer patients to access new treatments and serve as arenas for learning and competence development for health care workers. In addition to this, clinical studies can significantly contribute to financial savings for the health care system through the provision of drugs. The extent of these savings have not been evaluated before.</div></div><div><h3>Materials and Methods</h3><div>We assessed the financial savings from drugs provided in clinical studies conducted at Oslo Myeloma Center between 2015 and 2021. Only drugs that had marketing license or another equivalent drug with marketing license were considered to estimate savings.</div></div><div><h3>Results</h3><div>A total of 314 patients across 24 different studies were given treatment with drugs possessing marketing license. Drugs approved for clinical use and reimbursed by the national health care system gave a financial saving of 20.3 million USD and was considered a direct saving. Drugs not approved for clinical use, but having equivalent approved alternatives yielded a financial saving of 4.7 million USD.</div></div><div><h3>Conclusion</h3><div>Clinical studies not only offer new opportunities for patients and advancements in medical treatment and knowledge but also contribute significantly to financial saving for the health care system through reduced drug expenses.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 1","pages":"Pages e62-e69"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079447","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}

{"title":"Characteristics and Treatment Patterns of Long-surviving Patients With Multiple Myeloma: Over 13 Years of Follow-up in the ConnectⓇ MM Registry","authors":"Howard R. Terebelo ,&nbsp;James Omel ,&nbsp;Lynne I. Wagner ,&nbsp;James W. Hardin ,&nbsp;Robert M. Rifkin ,&nbsp;Sikander Ailawadhi ,&nbsp;Brian G.M. Durie ,&nbsp;Mohit Narang ,&nbsp;Kathleen Toomey ,&nbsp;Cristina J. Gasparetto ,&nbsp;Prashant Joshi ,&nbsp;Edward Yu ,&nbsp;E. Dawn Flick ,&nbsp;Ying-Ming Jou ,&nbsp;Hans C. Lee ,&nbsp;Rafat Abonour ,&nbsp;Sundar Jagannath","doi":"10.1016/j.clml.2024.11.001","DOIUrl":"10.1016/j.clml.2024.11.001","url":null,"abstract":"<div><h3>Background</h3><div>Over the last 15 years, improvements in patient management and treatments have been associated with longer survival in patients with multiple myeloma (MM). The Connect MM Registry is a long-running, US, multicenter, prospective observational cohort study of patients with newly diagnosed MM (NDMM). We assessed the demographics, clinical characteristics, and treatment patterns of long-term survivors (LTS) enrolled in this registry.</div></div><div><h3>Methods</h3><div>Adults with NDMM (<em>n</em> = 3,011) were enrolled from 250 community, academic, and government sites across the US from 2009-2016. Baseline characteristics, treatment patterns, quality of life (QoL), and overall survival (OS) were examined among LTS, defined as patients with follow-up of ≥ 8 years after enrollment.</div></div><div><h3>Results</h3><div>As of February 7, 2023, 518 patients were LTS and 2,493 were non-LTS. LTS were generally younger and had better performance status at enrollment compared with non-LTS. Most (65%) LTS received stem cell transplants and few (2%) experienced disease progression within 6 months of starting first line of therapy. At data cutoff, 63% of LTS were still on treatment at their most recent visit. QoL scores and QoL questionnaire completion rates were consistently higher among LTS than non-LTS. The estimated 8-year OS rate of all patients enrolled in the registry was 40%, comparable to an observed 8-year survival of 39% from the Surveillance, Epidemiology, and End Results (SEER) database.</div></div><div><h3>Conclusion</h3><div>This analysis provides insights on long-surviving patients with MM using real-world data and therefore presents generalizability beyond data obtained in long-term follow-up of clinical trials, underscoring the need for longitudinal follow-up through registries.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 1","pages":"Pages 58-66"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738660","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}

{"title":"Discontinuation of Tyrosine Kinase Inhibitor Therapy and Treatment Free Remission (TFR) in Chronic Myeloid Leukemia: Successful Achievement of TFR in More Than Two-Third of Patients in a Real-World Practice","authors":"Aamer Aleem ,&nbsp;Naila A. Shaheen ,&nbsp;Farjah Algahtani ,&nbsp;Ahmed Jamal ,&nbsp;Nora Alkhudair ,&nbsp;Mashail Alghafis ,&nbsp;Zafar Iqbal ,&nbsp;Hajar Wan Zuki Siti ,&nbsp;Abin Thomas ,&nbsp;Bader Alahmari ,&nbsp;Hind Salama ,&nbsp;Giamal Gmati ,&nbsp;Mohsen Alzahrani ,&nbsp;Ayman Alhejazi ,&nbsp;Mansour Alfayez ,&nbsp;Abdullah Alrajhi ,&nbsp;Mohammed A. Marei ,&nbsp;Ahmed Alaskar","doi":"10.1016/j.clml.2024.08.006","DOIUrl":"10.1016/j.clml.2024.08.006","url":null,"abstract":"<div><h3>Background</h3><div>Discontinuation of TKI therapy and treatment-free remission (TFR) have become new goals for chronic-phase chronic myeloid leukemia (CP-CML). The aim of this study was to estimate the TFR post discontinuation of TKI therapy at 3 tertiary-care centers.</div></div><div><h3>Patients and Methods</h3><div>CP-CML patients aged ≥16 years who had an attempt to discontinue TKI therapy till June 2022, were eligible. The collected data included patients’ demographics, prognostic score, type and duration of TKI therapy, response dates, relapse dates, response to re-initiation of TKI therapy, and risk factors for relapse.</div></div><div><h3>Results</h3><div>Fifty-five patients (35, 63.6% females) with a median age of 40 (range 16-74) years at diagnosis discontinued therapy. Forty-eight (87.3%) patients received imatinib as first line therapy. Twenty-nine (52.7%) patients were receiving imatinib at the time of TKI-discontinuation. Median time from diagnosis to TKI discontinuation was 86 months (IQR 60;132) and median duration of TKI therapy after achieving DMR was 66 months (IQR 47;114). After a median follow up of 34 (IQR 12;68) months, 15 (27.3%) patients relapsed. Median time to relapse was 5 months (range 2-38). Most of the relapses occurred during the first 6 months except 3 (20%) patients. All the relapsed patients achieved MMR after a median of 3 (range 2-6) months after restarting TKI therapy. None of the patients progressed to advanced-phase.</div></div><div><h3>Conclusion</h3><div>Our experience confirms that discontinuation of TKI therapy in CP-CML patients is feasible and safe in routine clinical practice, and can achieve TFR in more than two-third of carefully selected patients.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 1","pages":"Pages e50-e56"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281222","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":"CD10-Positive Lymphoplasmacytic Lymphoma: A Diagnostic Pitfall","authors":"Yaping Ju ,&nbsp;Sophie Stuart ,&nbsp;Yue Zhao ,&nbsp;Yi Xie ,&nbsp;Luis F. Carrillo ,&nbsp;Imran Siddiqi ,&nbsp;Ling Zhang ,&nbsp;Endi Wang","doi":"10.1016/j.clml.2024.09.004","DOIUrl":"10.1016/j.clml.2024.09.004","url":null,"abstract":"","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 1","pages":"Pages 23-25"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342792","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":"Deep Molecular Response Rate in Chronic Phase Chronic Myeloid Leukemia: Eligibility to Discontinuation Related to Time to Response and Different Frontline TKI in the Experience of the Gimema Labnet CML National Network","authors":"Massimo Breccia ,&nbsp;Rosalba Cucci ,&nbsp;Giovanni Marsili ,&nbsp;Fausto Castagnetti ,&nbsp;Sara Galimberti ,&nbsp;Barbara Izzo ,&nbsp;Federica Sorà ,&nbsp;Simona Soverini ,&nbsp;Monica Messina ,&nbsp;Alfonso Piciocchi ,&nbsp;Massimiliano Bonifacio ,&nbsp;Daniela Cilloni ,&nbsp;Alessandra Iurlo ,&nbsp;Giovanni Martinelli ,&nbsp;Gianantonio Rosti ,&nbsp;Fabio Stagno ,&nbsp;Paola Fazi ,&nbsp;Marco Vignetti ,&nbsp;Fabrizio Pane","doi":"10.1016/j.clml.2024.08.009","DOIUrl":"10.1016/j.clml.2024.08.009","url":null,"abstract":"<div><h3>Background</h3><div>In the last decade, TKIs improved the overall survival (OS) of chronic myeloid leukemia (CML) patients who achieved a deep and sustained molecular response (DMR, defined as stable MR4 and MR4.5). Those patients may attempt therapy discontinuation. In our analysis, we report the differences in eligibility criteria due to time of response and different TKI used as frontline treatment analyzed in a large cohort of CP-CML patients.</div></div><div><h3>Methods</h3><div>Data were exported by LabNet CML, a network founded by GIMEMA in 2014. The network standardized and harmonized the molecular methodology among 51 laboratories distributed all over Italy for the diagnosis and molecular residual disease (MRD) monitoring.</div></div><div><h3>Results</h3><div>Out of 1777 patients analyzed, 774 had all evaluable timepoints (3, 6, and 12 months). At 3 months, 40 patients obtained ≥MR4: of them 14 (3.6%) with imatinib, 8 (5.8%) with dasatinib, and 18 (7.4%) with nilotinib (<em>P</em> = .093); at 6 months, 146 patients were in MR4: 42 (11%) with imatinib, 38 (28%) with dasatinib, and 66 (27%) with nilotinib (<em>P</em> &lt; .001). At 12 months, 231 patients achieved a DMR: 85 (22%) with imatinib, 55 (40%) with dasatinib and 91 (38%) with nilotinib (<em>P</em> &lt; .001). Achieving at least ≥MR2 at 3 months, was predictive of a DMR at any timepoint of observation: with imatinib 67% versus 30% of patients with &lt;MR2, with dasatinib 66% versus 28% of patients with &lt;MR2, and with nilotinib 75% versus 30% of patients with &lt; MR2 (<em>P</em> &lt; .001). At the same time point, achieving at least ≥MR3 is even more predictive of a DMR at any timepoint: 89% versus 38% of patients with &lt;MR3 with imatinib (<em>P</em> &lt; .001), 84% versus 40% of patients with &lt;MR3 with dasatinib (<em>P</em> &lt; .001), and 89% versus 49% of patients with &lt;MR3 with nilotinib (<em>P</em> &lt; .001). Of 908 patients who reached a DMR, 461 (51%) lost it: the loss of response after &gt;2 years was significant for patients who at 3 months had ≥MR2 (18% vs. 9.9% of pts with &lt;MR2, <em>P</em> = .038).</div></div><div><h3>Conclusion</h3><div>In conclusion, reaching ≥MR2 and a MR3 at 3 months it seems predictive of a DMR at any time point. Considering the prerequisite for a discontinuation with a sustained DMR only a minority of patients can be eligible for the discontinuation, regardless the frontline treatment received.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 1","pages":"Pages e34-e39"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342793","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 Update and Next Questions: Current and Emerging Therapies for Systemic Mastocytosis","authors":"Helen T. Chifotides,&nbsp;Prithviraj Bose","doi":"10.1016/j.clml.2024.06.005","DOIUrl":"10.1016/j.clml.2024.06.005","url":null,"abstract":"<div><div>Systemic mastocytosis (SM) is a heterogeneous myeloid neoplasm, characterized by clonal proliferation of mast cells (MCs) in ≥ 1 extracutaneous organs, including the bone marrow (BM) and gastrointestinal tract. Aberrant MC proliferation is driven by mutation <em>KIT</em> D816V in <strong>≈</strong>90−95% of SM patients. Indolent SM (ISM) is the most common SM subtype with various symptoms that can be severe. Advanced SM (AdvSM) has markedly poor prognosis. The advent of KIT inhibitors, targeting mutant KIT and neoplastic MCs, led to a paradigm shift in SM management and markedly improved outcomes. Midostaurin inaugurated the era of KIT inhibitors and was approved for AdvSM in 2017. Avapritinib is the first highly potent and selective inhibitor of KIT D816V that was approved to treat AdvSM and symptomatic ISM (platelets ≥ 50 × 10⁹/L), in the US, in 2021 and 2023, respectively. Pooled analysis of the EXPLORER and PATHFINDER studies, assessing avapritinib in AdvSM, demonstrated rapid and profound reductions (≥ 50%) in markers of MC burden, high response rates (71−75%), and prolonged survival. In the PIONEER study, avapritinib significantly and rapidly improved symptoms/quality of life, and reduced markers of MC burden in ISM patients. The investigational agents bezuclastinib and elenestinib are highly potent and selective inhibitors of KIT D816V with minimal blood-brain barrier penetration. Bezuclastinib reduced markers of MC burden by ≥ 50% in <strong>≈</strong>50% of AdvSM patients and <strong>≈</strong>90−100% of nonAdvSM patients and reduced symptoms (≥ 50%) in the APEX and SUMMIT studies, respectively. Elenestinib demonstrated dose-dependent efficacy in reducing MC burden markers and improved symptoms in ISM patients in the HARBOR study.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 1","pages":"Pages 1-12"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016571","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}