![]() ![]() 10-12 Among patients with mutated MYD88, the concurrent presence of a CXCR4 mutation adversely impacted response rates, response kinetics, and 5-year PFS (38% vs. Patients wild-type (WT) for both MYD88 and CXCR4 had no major responses and a median PFS of 5 months to ibrutinib. A notable finding was the impact of MYD88 and CXCR4 mutations on ibrutinib outcomes. 10, 11 Responses to ibrutinib were durable with an estimated 5-year progression-free survival (PFS) and overall survival (OS) of 54% and 87%, respectively. 10 Ibrutinib monotherapy was highly active with an overall response rate (ORR) of 91%, major response rate (MRR) of 79%, and very good partial response rate (VGPR) of 30% with prolonged follow-up. ![]() The regulatory approval of ibrutinib was based on the results from a multi-center, single-arm, phase II trial of 63 previously treated WM patients. In 2015, ibrutinib became the first approved agent by the United States Food and Drug Administration and European Medicines Agency for the treatment of symptomatic WM patients. 4, 5 Mutations in the C-terminal domain of CXCR4 are typically subclonal and support intrinsic ibrutinib resistance through upregulation of AKT and ERK1/2 signaling. 4, 5 Both BTK and HCK are targeted by ibrutinib. 2, 3 Mutated MYD88 triggers NF-kB pro-survival signaling via Bruton’s tyrosine kinase (BTK) and interleukin-1 receptor-associated kinase 1 (IRAK1)/IRAK4, and transactivates hematopoietic cell kinase (HCK). 1 Whole-genome sequencing has identified highly recurrent somatic mutations in MYD88 (95-97%) and CXCR4 (30-40%) in WM patients. Waldenström macroglobulinemia (WM) is an immunglobulin M (IgM)-secreting lymphoplasmacytic lymphoma. Our findings reveal that continuation of ibrutinib until subsequent treatment is associated with improved disease control and clinical outcomes. TP53 mutations were associated with shorter OS, while acquired BTK C481S mutations had no impact. Response to salvage therapy was associated with better OS after ibrutinib (hazard ratio 0.08, 95% CI: 0.02-0.38). The 5-year overall survival (OS) following discontinuation of ibrutinib was 44% (95% CI: 26-75). Quadruple-class (rituximab, alkylator, proteasome inhibitor, ibrutinib) exposed disease (odds ratio 0.20, 95% CI: 0.05-0.73) and salvage therapy ≤7 days after discontinuing ibrutinib (OR 4.12, 95% CI: 1.07-18.9) were identified as independent predictors of a response to salvage therapy. The overall and major response rates to salvage therapy were 56% and 44%, respectively, and the median duration of response was 48 months (95% CI: 34-not reached). The median time to salvage therapy after ibrutinib cessation was 18 days (95% confidence interval : 13-27). Forty-eight patients (94%) received salvage therapy after ibrutinib. Following discontinuation of ibrutinib, a rapid increase in serum immunoglobulin M level was observed in 60% (29/48) of evaluable patients, of whom ten acutely developed symptomatic hyperviscosity. The median time between ibrutinib initiation and discontinuation was 2 years (range, 0.4-6.5 years). We therefore evaluated the natural history and treatment outcomes in 51 WM patients with acquired resistance to ibrutinib monotherapy. He's put together a series of tutorials on Vimeo for mFlare in FCPX and Motion.Ibrutinib is highly active and produces long-term responses in patients with Waldenström macroglobulinemia (WM), but acquired resistance can occur with prolonged treatment. The good news is that MotionVFX has also posted a free trial version so you can take the flares for a test drive yourself.įCP.co friend Robin S. MFlare 2 is priced at $149, existing mFlare 1 owners can get the update for $79. It uses values from the colour spectrum to match the flare into the video in a more convincing way. A lot easier and more accurate than keyframing. The tracking controls can be found onscreen in the bottom left hand corner.Īlso new is an innovative colour picker for the flares. The first is Mocha tracking which will automatically track an item onscreen so that a flare can be attached. Onscreen controls position the various elements of the flare to get the spread just right as if it was being caused by internal lens reflections. The GUI has controls for enabling or disabling elements of the flare and sliders for settings such as brightness, size and smoothness. ![]() The flares are not motion templates, each of the 100 effects in the FCPX or Motion browser is a preset for the native plugin which opens up with its own user GUI. ![]()
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