Publications by authors named "Andrew R Branagan"
Multiple myeloma (MM) remains incurable despite novel therapeutics. A major contributor to the development of relapsed/refractory and resistant MM is extraosseous extramedullary disease (EMD), whose molecular biology is still not fully understood. We analyzed 528 MM patients who presented to our institution between 2014 and 2021 and who had undergone molecular testing.
View Article and Find Full Text PDFElotuzumab is an approved monoclonal antibody targeting SLAMF7 on plasma and NK cells that enhances the activity of lenalidomide, pomalidomide, and bortezomib in multiple myeloma (MM). The OPTIMISMM study showed improved outcomes with the combination of pomalidomide, bortezomib, and dexamethasone (PVd) in relapsed/refractory MM. We therefore studied adding elotuzumab to PVd (elo-PVd) in relapsed/refractory MM in a multicenter phase 2 trial.
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- 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.
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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
- CAR T cell therapies are effective but can cause serious side effects like cytokine release syndrome and immune-related neurotoxicity, leading to neutropenia.
- In a study of patients with lymphoma, those who received prophylactic G-CSF before CAR T had faster recovery of neutrophils but experienced higher rates of severe CRS.
- In multiple myeloma patients, timing of G-CSF administration didn't show a significant impact on toxicities, indicating a need for more research to determine the best G-CSF approach following CAR T treatments.
Although caregivers of patients with multiple myeloma (MM) play a critical role in supporting their loved ones throughout the illness course, studies examining caregiver quality of life (QOL), psychological distress, and prognostic awareness are lacking. We conducted a cross-sectional, multisite study of patients undergoing treatment with MM and their caregivers. Eligible caregivers were enrolled to 1 of 3 cohorts based on lines of therapy.
View Article and Find Full Text PDFZanubrutinib for the treatment of adults with Waldenstrom macroglobulinemia.
Expert Rev Anticancer Ther
May 2022
Introduction: The development of Bruton tyrosine kinase (BTK) inhibitors has significantly changed the treatment landscape for patients with Waldenström macroglobulinemia (WM). Ibrutinib was the first BTK inhibitor to receive FDA approval for this disease, but in recent years additional more selective BTK inhibitors have become available. Zanubrutinib, the most recently FDA-approved therapy for WM, has demonstrated comparable efficacy regarding hematologic response, but with an improved side effect profile compared to other BTK inhibitors.
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- Waldenström Macroglobulinemia (WM) is a rare blood cancer involving abnormal lymphoplasmacytic cells in the bone marrow, leading to the production of excess IgM.
- About 90-95% of WM patients have mutations in genes MYD88 and CXCR4, influencing treatment options.
- Current treatments often include rituximab with various chemotherapy agents and newer targeted therapies like BTK inhibitors, with ongoing research into combination therapies to improve effectiveness and reduce side effects.
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- The HCK family kinase is upregulated and activated by mutated MYD88 in specific types of lymphomas, triggering key signaling pathways like BTK, AKT, and ERK.
- In MYD88Mut lymphoma cells, HCK enhances SYK activation, while the SFK LYN plays a lesser role in certain lymphoma types, such as Waldenstrom macroglobulinemia.
- Overexpression of HCK leads to persistent activation of SYK, and inhibiting HCK reduces SYK activity, indicating that HCK could be a potential therapeutic target for treating MYD88Mut B-cell lymphomas.
Background: Multiple myeloma (MM) is an incurable hematologic malignancy requiring long-term, continuous therapy. Despite its chronic and unrelenting course, studies examining quality of life (QOL), psychological distress, and perceptions of prognosis by line of therapy are lacking.
Methods: The authors conducted a cross-sectional, multisite study of patients undergoing treatment for MM (excluding maintenance) between June 2020 and January 2021.
Article Synopsis
- BTK inhibitors, like ibrutinib, are currently the only FDA-approved treatments for Waldenström macroglobulinemia (WM), but the factors affecting their effectiveness were not fully understood.
- In a study of 319 WM patients on ibrutinib, CXCR4 mutations and low platelet counts were linked to worse treatment responses and shorter progression-free survival, leading to a proposed scoring system based on these factors.
- The research found that older age (65+) greatly impacts overall survival and confirmed the significance of CXCR4 mutations as predictors for patient outcomes on ibrutinib.
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- BCL2 is overexpressed in Waldenström macroglobulinemia (WM) cells, and venetoclax, a BCL2 inhibitor, shows potential for causing cell death in these cases, yet its effectiveness in WM needed further investigation.
- A phase II clinical trial demonstrated venetoclax's promising results in 32 treated patients, with overall response rates of 84%, and a median progression-free survival of 30 months.
- The treatment was generally well-tolerated, with neutropenia as the main side effect, and the presence of certain mutations did not influence the overall treatment outcomes.
As the prognosis for multiple myeloma (MM) has significantly improved and patients remain on therapy longer, there is a need for supportive care interventions to optimize patient quality of life (QOL) and functional status over the course of cancer treatment. MM is characterized by a significant symptom burden and a relatively lower QOL compared to other cancers. This review evaluates the role of healthy lifestyle behaviors in improving both the physical functioning and psychological well-being of the MM population.
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- - This study evaluated the effectiveness of ibrutinib, a daily treatment for 30 patients newly diagnosed with Waldenstrom macroglobulinemia (WM), showing promising response rates: 100% overall response, 87% major response, and 30% very good partial response (VGPR) after 50 months of follow-up.
- - Patients with CXCR4 mutations had lower VGPR rates (14% vs. 44%) and longer times to achieve major responses compared to those without mutations, indicating a possible impact of these mutations on treatment outcomes.
- - Despite some treatment-related side effects, including fatigue and atrial fibrillation in 20% of patients, the study concluded that ibrutinib
Article Synopsis
- MYD88 and CXCR4 mutations are frequently found in Waldenström macroglobulinemia (WM) and the CXCR4 mutation can affect patient response to BTK inhibitors.
- A phase 1 trial tested the CXCR4-antagonist ulocuplumab combined with ibrutinib, enrolling 13 symptomatic patients, which resulted in significant declines in median immunoglobulin M levels and bone marrow disease.
- The study achieved high response rates, with a 2-year progression-free survival of 90%, while showing that combining the two treatments is feasible and well-tolerated, despite some adverse events.
Ibrutinib is highly active and produces long-term responses in patients with Waldenström macroglobulinemia (WM), but acquired resistance can occur with prolonged treatment. We therefore evaluated the natural history and treatment outcomes in 51 WM patients with acquired resistance to ibrutinib monotherapy. The median time between ibrutinib initiation and discontinuation was 2 years (range, 0.
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- * Different testing methods for detecting the CXCR4 S338X variant may lead to inconsistent results in clinical trials, complicating treatment strategies.
- * The study found that while targeted next-generation sequencing often missed CXCR4 mutations, combining allele-specific PCR with CD19 cell selection greatly improved detection accuracy, although sensitivity was reduced in cases with low bone marrow involvement and varied mutation presence.
Patients with plasma cell dyscrasias (PCDs) experience an increased burden of influenza, and current practice of single-dose annual influenza vaccination yields suboptimal protective immunity in these patients. Strategies to improve immunity to influenza in these patients are clearly needed. We performed a randomized, double-blind, placebo-controlled clinical trial comparing tandem Fluzone High-Dose influenza vaccination with standard-of-care influenza vaccination.
View Article and Find Full Text PDFWaldenström Macroglobulinemia (WM) is an incurable hematologic malignancy characterized by lymphoplasmacytic infiltration of the bone marrow and the presence of monoclonal immunoglobulin (IgM). Although a portion of WM patients may experience a relatively indolent course, patients may experience IgM-related morbidity and/or disease-related mortality. This underscores the need for novel approaches to improve response and survival rates.
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