Publications by authors named "Catherine A Flynn"
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
- 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
- * The study involved three participants who received dasatinib (100 mg daily) for up to 24 cycles, but the best outcome was only stable disease.
- * Due to minimal responses and one patient's dose reduction from side effects, the study was concluded early, indicating dasatinib may not be effective for WM patients progressing on ibrutinib.
Article Synopsis
- 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.
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.
Article Synopsis
- 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.
Article Synopsis
- - 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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- * Analysis of two patient groups treated with ibrutinib found that around 64%-71% achieved a partial response or better within six months, with significantly better three-year PFS rates for those who did.
- * Results suggest that achieving at least a partial response at six months is linked to improved PFS, indicating it could serve as a valuable marker in future clinical trials for Bruton tyrosine kinase inhibitors in treating WM.
Article Synopsis
- Daratumumab showed a 23% overall response rate in previously treated patients with Waldenström's macroglobulinemia (WM).* -
- Patients treated with daratumumab had a median progression-free survival (PFS) of 2 months.* -
- The two patients who had a partial response to the treatment had higher baseline levels of CD38 fluorescent intensity in their plasma cells.*
Article Synopsis
- * Patients showed significant response rates with a median time to response of 2 months and a 96% overall response rate, while mutations in CXCR4 influenced the timelines of response slightly.
- * The treatment was well-tolerated with no severe side effects, and demonstrated promising long-term outcomes, including a median progression-free survival of 40 months, indicating IDR is a safe and effective first-line option for symptomatic WM
Article Synopsis
- * A study analyzed the differences in clinical characteristics and treatment outcomes between WM patients receiving ibrutinib on clinical trials (ON trial) and those off trials (OFF trial), finding similar response rates and survival outcomes.
- * Both treatment-naïve and previously treated patients showed effectiveness of ibrutinib; the study validates its efficacy compared to previous clinical trial results.
Article Synopsis
- The study analyzed 31 cases of non-IgM lymphoplasmacytic lymphoma (LPL) and compared them with 93 cases of Waldenström macroglobulinemia (WM), matching participants by age, sex, and diagnosis year.
- Non-IgM LPL cases exhibited fewer mutations and shorter times to treatment compared to WM controls, but had higher chances of extramedullary disease.
- Despite these differences in clinical features and treatment options, both groups had similar response rates and overall survival outcomes.
Article Synopsis
- Rituximab-based treatments are frequently used as initial therapy for patients with symptomatic Waldenström macroglobulinemia (WM), and a study found that some patients show improvement in their response even after finishing treatment.
- Out of 178 patients analyzed, 38% who received maintenance therapy and 31% who were observed experienced a significant drop (≥25%) in serum IgM levels several months or years after completing their regimen.
- Factors such as lower baseline hemoglobin, high bone marrow involvement, CXCR4 mutations, and elevated serum IgM levels were linked to a lower chance of improved response, which was associated with better progression-free survival and overall survival rates in WM patients.