Venetoclax is efficacious in relapsed/refractory t(11;14) multiple myeloma, thus warranting investigation in light-chain amyloidosis (AL). This retrospective cohort includes 43 patients with previously treated AL, from 14 centers in the US and Europe. Thirty-one patients harbored t(11;14), 11 did not, and one t(11;14) status was unknown. Patients received a venetoclax-containing regimen for at least one 21- or 28-day cycle; the median prior treatments was three. The hematologic response rate for all patients was 68%; 63% achieved VGPR/CR. t(11;14) patients had higher hematologic response (81% vs. 40%) and higher VGPR/CR rate (78% vs. 30%, odds ratio: 0.12, 95% CI 0.02–0.62) than non-t(11;14) patients. For the unsegregated cohort, median progression-free survival (PFS) was 31.0 months and median OS was not reached (NR). For t(11;14), median PFS was NR and for non-t(11;14) median PFS was 6.7 months (HR: 0.14, 95% CI 0.04–0.53). Multivariate analysis incorporating age, sex, prior lines of therapy, and disease stage suggested a risk reduction for progression or death in t(11;14) patients. Median OS was NR for either subgroup. The organ response rate was 38%; most responders harbored t(11;14). Grade 3 or higher adverse events occurred in 19% with 7% due to infections. These promising results require confirmation in a randomized clinical trial.
Asymptomatic carotid stenosis patients with prior cerebral infarction have a higher stroke risk during long-term follow-up than those without prior cerebral infarction. Evidence of prior ischemic events might help identify patients in whom carotid intervention is particularly beneficial.
Daratumumab is approved for use in newly diagnosed and relapsed/refractory multiple myeloma (MM), however the patients most likely to benefit from its addition to standard anti‐myeloma therapy is unclear. This meta‐analysis included 2340 newly diagnosed MM patients (1982 with standard risk and 358 with high risk cytogenetics) and 673 patients with relapsed/refractory MM (513 with standard risk and 160 with high risk cytogenetics) to assess which cytogenetic subgroups derived PFS benefit from Daratumumab. Studies included were the CASSIOPEIA, MAIA and ALCYONE (for newly diagnosed MM) and the CASTOR and POLLUX trials (for relapsed/refractory MM). Daratumumab's addition led to a clear benefit in standard risk newly diagnosed MM (HR 0.43; 95% CI, 0.35‐0.53; P < .05) and both high and standard risk relapsed/refractory disease (HR 0.28; 95% CI, 0.21‐0.36; P < .05 and HR 0.48; 95% CI, 0.30‐0.76; P < .05, respectively). No clear benefit was seen in newly diagnosed high risk MM. These findings fail to demonstrate PFS benefit from Daratumumab's addition in high risk newly diagnosed MM. Data forthcoming from the GRIFFIN and MASTER trials may increase the power of the study and provide a definitive answer. Daratumumab remains important in standard risk upfront and relapsed/refractory MM and high risk relapsed/refractory MM.
PURPOSE No established treatments exist for relapsed/refractory systemic light-chain (AL) amyloidosis. Bendamustine has shown potential in the treatment of multiple myeloma. We conducted a phase II, multicenter trial to assess the efficacy and safety of bendamustine with dexamethasone (ben-dex) in patients with persistent or progressive AL amyloidosis after ≥ 1 prior therapy. METHODS The trial enrolled 31 patients who received bendamustine on days 1 and 2 (100 mg/m2 intravenously) with 40 mg of weekly dexamethasone in 28-day cycles until disease progression or up to 6 cycles after complete hematologic response. The primary objective was the rate of partial hematologic response (PR) or better. RESULTS Patients received a median of 4 cycles (range, 2-12 cycles) with 57% of patients achieving a PR or better (11% complete response, 18% very good PR). The overall organ response was 29% among the 24 patients who had measurable organ involvement. Treatment was well tolerated with no grade 5 treatment-related adverse events (AEs). Sixty-five percent of patients had a therapy-related grade 3-4 AE. The most common AEs included myelosuppression, fatigue, and nausea/vomiting. The median overall survival was 18.2 months (95% CI, 11.3 to 43.8 months), and hematologic response was associated with prolonged survival ( P = .0291). The median progression-free survival was 11.3 months (95% CI, 5.0 to 15.4 months). CONCLUSION Overall, ben-dex is a viable treatment option with substantial efficacy and limited toxicity for patients with pretreated AL amyloidosis who have limited therapeutic options. This trial was registered at (ClinicalTrials.gov identifier: NCT01222260 ).
Technology may help adolescents with chronic illnesses overcome barriers to accessing peer support, which has been associated with better quality of life and health outcomes. This review aimed to describe technology-based peer support interventions for adolescents with chronic illness following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Of 3781 articles identified, 32 met inclusion criteria. The most common technologies were websites with discussion forums (n = 18), chat messaging (n = 9), and video conferencing (n = 7). Most studies (69%) focused on feasibility and had small sample sizes. Results support the feasibility and acceptability of these interventions. Results suggested positive effects on social support, but were mixed on isolation, quality of life, and disease self-management. There were too few adequately powered randomized controlled trials to determine efficacy of these interventions at this time. Future work should use rigorous methods to evaluate efficacy and account for rapid shifts in technology for adolescent communication.
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