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7538 Background: Continuous therapy with once-daily ibrutinib (Ibr) is associated with long-term PFS in pts with B-cell malignancies. Dose reduction is a potential AE management approach that may optimize treatment outcomes. We evaluated outcomes with dose reductions in Ibr-treated pts with cardiac AEs. Methods: Data were pooled for Ibr-treated pts from 10 studies of CLL (n=781), mantle cell lymphoma (MCL; n=250), marginal zone lymphoma (MZL; n=63) or Waldenström macroglobulinemia (WM; n=169). Cardiac AEs, initial and recurrent, were identified by preferred terms within the cardiac disorders system organ class. Recurrence was defined as an AE of same or worse grade, and was measured up to 30 days after last dose of ibrutinib or start of next-line therapy, whichever occurred earlier. Results: Overall, 234/1263 pts (19%) had cardiac AEs of any grade. Twelve pts were excluded from the analysis: 9 who had a dose reduction prior to a cardiac AE (0.7%) and 3 who had a fatal cardiac AE with no prior cardiac AE (0.2%). Of the remaining 222 pts with grade 1-4 cardiac AEs, 22 (10%) had Ibr dose reduction to 420 mg (n=3), 280 mg (n=10), or 140 mg (n=9) after a cardiac AE. These pts (n=22) tended to be older (≥75 y: 45% vs 29%), less heavily pretreated (≥1 prior therapy: 45% vs 73%), and with a lower Ibr discontinuation rate (23% vs 48%) than those without dose reduction (n=200). Recurrence of the same cardiac AEs at the same or worse severity was less frequent in pts with dose reductions, both overall (14% vs 18%) and as serious AEs (5% vs 10%). No pt died due to cardiac AE recurrence. Among pts with cardiac AEs who started with the 420 mg Ibr dose (177/222; excludes 45 patients with MCL or MZL who per label start with 560 mg dose), no cardiac AE recurred at same or worse severity in the subset with dose reductions (Table). PFS was not negatively impacted by dose reduction, both overall (n=22; median PFS not reached [NR], 24-mo PFS: 91%), and in those who started with the 420 mg dose (n=18; median PFS NR; 24-mo PFS, 94%). Conclusions: Dose reduction for cardiac AEs may enable pts to continue to benefit from long-term Ibr and mitigate the risk of cardiac AE recurrence or worsening. Clinical trial information: NCT01105247 , NCT01236391 , NCT01578707 , NCT01722487 , NCT01611090 . [Table: see text]

Background Dietary guidelines typically recommend limiting the intake of fresh red meat, yet evidence linking red meat consumption with adverse health outcomes is inconsistent. Objective To assess the level of evidence from existing systematic reviews and meta-analyses and analyze the association between high consumption of red meat and cancer risk and adverse health outcomes. Methods Eight databases were searched to collect systematic reviews and meta-analyses from database inception to December 2022. Two independent reviewers screened and extracted data and used the AMSTAR 2 tool to evaluate methodological quality of the included studies. Meta-analysis was conducted using STATA 17.0. Results A total of 18 studies were included, of which 5 were rated as high quality, 4 as medium quality, 6 as low quality, and 3 as extremely low quality. Of the 9 SRs/MAs included, primary studies with overlap were identified, and 14 studies were eventually included. The meta-analysis results showed that compared with the lowest intake of red meat, the highest intake of red meat was associated with an increased risk of colorectal cancer (OR 1.21, 95% CI 1.07-1.37), gastric cancer (OR 1.37, 95% CI 1.18-1.59), non-Hodgkin's lymphoma (OR 1.10.95% CI 1.02-1.19), stroke (RR 1.11, 95% CI 1.03-1.20), type 2 diabetes (RR 1.19 95% CI 1.04-1.37), and ischemic heart disease (RR 1.09, 95% CI 1.06-1.12), as well as a negative effect on total cholesterol (WMD 0.264, 95% CI 0.144-0.383), triglycerides (WMD -0.181, 95% CI -0.349 to -0.013), low-density lipoprotein (WMD 0.198, 95% CI 0.065-0.330), and high-density lipoprotein (WMD -0.065, 95% CI -0.109 to -0.020). However, the associations with breast cancer (RR 1.05 95% CI 1.00-1.11), glycemic control (WMD 0.040, 95% CI 0.049-0.129), and changes in body weight status [overweight (β 0.89, 95% CI 0.48-1.64); obesity (β 1.06, 95% CI 0.30-3.71)] were not significant. Conclusions This comprehensive umbrella review suggests that high consumption of red meat may increase the risk of colorectal cancer, gastric cancer, non-Hodgkin lymphoma, stroke, type 2 diabetes, and cardiovascular disease, and that reducing red meat intake is a key modifiable dietary factor for reducing risk. However, there was no significant correlation with breast cancer, kidney stones, age-related eye disease or changes in body weight.