Publications by authors named "Steven Treon"
Editorial Expression of Concern: Activation of NF-κB and upregulation of intracellular anti-apoptotic proteins via the IGF-1/Akt signaling in human multiple myeloma cells: therapeutic implications.
Oncogene
November 2024
Article Synopsis
- The ASPEN study is a Phase III clinical trial that compares the effectiveness of two drugs, zanubrutinib and ibrutinib, in treating patients with Waldenström macroglobulinemia (WM).
- A total of 201 patients participated, with 102 receiving zanubrutinib and 99 receiving ibrutinib, and the outcomes were evaluated using patient-reported questionnaires.
- Results indicated that zanubrutinib led to better improvements in health-related quality of life, particularly regarding symptoms like diarrhea and nausea/vomiting, as well as overall physical functioning and fatigue in patients who achieved a very good partial response to treatment.
Article Synopsis
- The study focuses on the prognosis of patients with Waldenström macroglobulinemia (WM) and reassesses traditional prognostic scoring systems in light of new therapies and genetic data.
- Researchers analyzed records of 889 treatment-naïve WM patients to identify clinical predictors influencing overall survival, leading to a new prognostic model based on factors like age and serum levels.
- The newly developed Modified Staging System for WM (MSS-WM) successfully categorizes patients into four distinct risk groups based on their clinical data, demonstrating significant differences in 5-year overall survival rates.
Article Synopsis
- Histologic transformation of Waldenström macroglobulinemia (HT-WM) usually results in a poor outlook when treated with standard therapies.* -
- This report presents the first cases of HT-WM being treated with chimeric antigen receptor T cells (CAR-T), which showed promising effectiveness.* -
- The treatment with CAR-T cells did not cause any unexpected side effects, indicating it might be a safer option for these patients.*
Article Synopsis
- BTK inhibitors have improved outcomes for mantle cell lymphoma (MCL) patients, but the disease remains incurable due to resistance issues.
- Research indicates that HCK, a Src-family tyrosine kinase, is linked to poor prognosis in MCL and its inhibition can limit cell growth and adhesion.
- The dual inhibitor KIN-8194 effectively targets both BTK and HCK, showing strong anti-growth effects on MCL cells regardless of their resistance to existing BTK inhibitors, suggesting its potential as a new treatment option.
Article Synopsis
- The phase 3 ASPEN trial compared the effectiveness of two BTK inhibitors, zanubrutinib and ibrutinib, in treating Waldenström macroglobulinemia, analyzing genetic mutations' impact on treatment response.
- The study found that patients with mutations in CXCR4 and TP53 had poorer responses and survival rates but those treated with zanubrutinib generally showed better outcomes than those given ibrutinib.
- Overall, the research indicated that zanubrutinib offers improved clinical outcomes for patients with specific mutations compared to ibrutinib, highlighting the importance of genetic testing in treatment decision-making.
Article Synopsis
- Mutations in the MYD88 and CXCR4 genes are frequently found in patients with Waldenström macroglobulinemia, affecting treatment responses and survival outcomes.
- Covalent BTK inhibitors (cBTKi) are effective in 70%-80% of WM patients, with individual mutation status influencing the effectiveness and occurrence of side effects.
- New treatment strategies, including pirtobrutinib or venetoclax, are available for those who develop resistance to cBTKis, with specific approaches recommended based on patient genetics and previous treatments.
Article Synopsis
- A clinical trial was conducted to investigate the effects of combining two drugs, ibrutinib and venetoclax, for treating symptomatic, treatment-naïve patients with MYD88-mutated Waldenström macroglobulinemia (WM).
- Out of 45 patients enrolled, 42% achieved a very good partial response (VGPR), and the study noted significant adverse events, including a concerning rate of ventricular arrhythmia.
- After a median follow-up of 24.4 months, the study reported strong progression-free survival (76%) and overall survival (96%) rates, even though it was terminated early due to safety concerns.
Article Synopsis
- The phase III ASPEN study showed that zanubrutinib is as effective as ibrutinib but has better safety for treating patients with Waldenström macroglobulinemia (WM).
- In a long-term follow-up, zanubrutinib demonstrated higher rates of very good partial response and complete response compared to ibrutinib in both cohorts of WM patients.
- Adverse events like diarrhea, muscle spasms, and hypertension were more common with ibrutinib, while zanubrutinib had a lower risk of treatment-related discontinuation.
Consensus Panel 4 (CP4) of the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11) was tasked with reviewing the current criteria for diagnosis and response assessment. Since the initial consensus reports of the 2nd International Workshop, there have been updates in the understanding of the mutational landscape of IgM related diseases, including the discovery and prevalence of MYD88 and CXCR4 mutations; an improved recognition of disease related morbidities attributed to monoclonal IgM and tumor infiltration; and a better understanding of response assessment based on multiple, prospective trials that have evaluated diverse agents in Waldenstrom's macroglobulinemia. The key recommendations from IWWM-11 CP4 included: (1) reaffirmation of IWWM-2 consensus panel recommendations that arbitrary values for laboratory parameters such as minimal IgM level or bone marrow infiltration should not be used to distinguish Waldenstrom's macroglobulinemia from IgM MGUS; (2) delineation of IgM MGUS into 2 subclasses including a subtype characterized by clonal plasma cells and MYD88 wild-type, and the other by presence of monotypic or monoclonal B cells which may carry the MYD88 mutation; and (3) recognition of "simplified" response assessments that use serum IgM only for determining partial and very good partial responses (simplified IWWM-6/new IWWM-11 response criteria).
View Article and Find Full Text PDFConsensus Panel 6 (CP6) of the 11th International Workshop on Waldenström's Macroglobulinemia (IWWM-11) was tasked with reviewing the state of the art for diagnosis, prognosis, and therapy of AL amyloidosis associated with Waldenström macroglobulinemia (WM). Since significant advances have been made in the management of AL amyloidosis an update for this rare disease associated with WM was necessary. The key recommendations from IWWM-11 CP6 included: (1) The need to improve the diagnostic process by recognizing red flags and using biomarkers and imaging; (2) The essential tests for appropriate workup; (3) The diagnostic flowchart, including mandatory amyloid typing, that improves the differential diagnosis with transthyretin amyloidosis; (4) Criteria for therapy response assessment; (5) State of the art of the treatment including therapy of wild type transthyretin amyloidosis associated with WM.
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- The Consensus Panel 1 (CP1) of IWWM-11 focused on updating guidelines for managing symptomatic, treatment-naïve Waldenstrom's Macroglobulinemia (WM) patients, asserting that watchful waiting is best for asymptomatic cases.
- Current first-line treatments include chemoimmunotherapy regimens like DRC and Benda-R, which are effective, usually well-tolerated, and cost-effective; covalent BTK inhibitors like zanubrutinib also provide a viable alternative, showing fewer side effects and better remissions compared to ibrutinib.
- The panel also noted the importance of testing for MYD88 and CXCR4 mutations prior to treatment, as these can influence the effectiveness of certain
Article Synopsis
- Waldenström macroglobulinaemia (WM) is linked to a MYD88 mutation that aids the growth of malignant cells, and ibrutinib is a key treatment that inhibits Bruton tyrosine kinase (BTK).
- A study found that 27% of WM patients required a dose reduction of ibrutinib due to side effects, with older patients and females experiencing more frequent reductions.
- After dose reduction, most patients (65%) reported improvements in side effects, and 79% maintained or enhanced their hematologic response during a three-year follow-up.
Article Synopsis
- Waldenström macroglobulinemia (WM) is a rare non-Hodgkin lymphoma marked by malignant lymphoplasmacytic cells in the bone marrow, where researchers studied the tumor microenvironment using mass cytometry (CyTOF).
- The study found a significant increase in specific B cell types and changes in immune cell populations, indicating that certain immune responses in the bone marrow are linked to better overall survival in WM patients.
- Results showed that immune checkpoints had a role in altering the immune landscape, and the effectiveness of the drug ibrutinib was connected to the levels of immature B cells and specific T cell subsets, highlighting CyTOF as a valuable tool for understanding WM and guiding treatments.
Bruton tyrosine kinase (BTK) inhibitors have taken a central role in the management of patients with Waldenström macroglobulinemia and are the only agents approved by the Food and Drug Administration (FDA) to treat these patients. Although associated with high rates of durable responses, unmet needs with BTK inhibitor therapy include indefinite duration therapy, high cost, scarcity of complete responses, and lower rates and shorter duration of response in patients with CXCR4 mutations. Herein, we review the data supporting the use of covalent BTK inhibitors, selected management issues, clinical trials with covalent BTK inhibitor combination regimens, and up-and-coming non-covalent BTK inhibitors.
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- * Researchers found that GPER1 is significantly increased in tumor cells of WM patients when compared to normal B cells.
- * The GPER1-selective agonist G-1 (Tespria) induces cell cycle arrest and apoptosis in cancer cells, activating the TP53 pathway and showing promise for further clinical development in WM treatment.