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With the introduction of targeted chemotherapy drugs, a new age of treatment for acute myeloid leukemia (AML) has begun. The promotion of the azacitidine+venetoclax combination regimen to first line of treatment in patients deemed ineligible for intensive chemotherapy marks the first of many novel combination regimens becoming part of national treatment guidelines. We review recent phase II and III clinical trials and conclude that these novel regimens offer significant increases in response rates, remission rates, and overall survival. The incidence of adverse events, the accrued time toxicity, and the healthcare costs, however, are increasing as well. Compared with clinical trials, older patients in the real world frequently present with an inferior baseline health status, which is associated with an increased risk of experiencing side effects. The key to reaping the maximum benefit of the new agents and their combination regimens therefore lies in sufficient attention being given to a patients' preexisting comorbidities, potential frailty, and quality of life. A systematic collaboration between hemato-oncologists and geriatricians can be a potent first step towards addressing the increased treatment intensity patients with AML experience under the novel regimens. In this narrative review article we provide an overview of recent and ongoing clinical trials, highlight encountered adverse events, discuss frailty assessment options, and outline an oncogeriatic care path for older patients with AML. [ABSTRACT FROM AUTHOR]

Treatment for myelodysplastic syndromes (MDS) is complex, options are limited, and insight into consecutive treatments is lacking. We performed this study to assess the outcomes in a real-world cohort of patients with MDS. An observational population-based study was performed using the HemoBase registry. Treatment patterns and overall survival (OS) were analyzed with Kaplan-Meier analyses. In 144 of 280 (51.4%) patients with MDS >50 years, first-line treatment was initiated. The median age was 75.1 years (range: 52.6–92.0); the majority were male (72.2%). Hypomethylating agents (HMA), intensive chemotherapy, lenalidomide, and erythropoiesis-stimulating agents (ESA) were given as first-line treatment to 31.1% (n = 45), 12.5% (n = 18), 2.8% (n = 4), and 53.5% (n = 77) of the population, respectively. The median treatment duration was 5.8 months (95% Confidence Interval [CI]: 1.1–10.4) for HMA, 1.7 months (95%CI: 0.9–2.6) for intensive chemotherapy, 10.8 months (95%CI: 4.7–17.0) for lenalidomide, and 14.8 months (95%CI: 11.4–18.1) for ESA. Consecutive treatments were given to 27.2% of patients. The main reasons for first-line treatment discontinuation were treatment failure (45.8%), toxicity (6.9%), or death (20.1%). Median OS after termination of the initial, second, and third treatment was 5.8 months (95%CI: 3.2–8.5), 9.3 months (95%CI: 0.0–19.6), and 1.0 months (95%CI: 0.0–5.1), respectively. This study shows the treatment outcomes in a real-world population of older patients with MDS. Treatment duration and median OS after treatment discontinuation were relatively limited. There is still an urgent need for new treatment options, strategies to further optimize duration of existing treatments, and communication of realistic treatment goals and expectations, especially for older, higher-risk patients with MDS with a poor prognosis. [ABSTRACT FROM AUTHOR]

While treatment strategies for multiple myeloma have evolved radically over the last decades, little is known about the risk of fractures for symptomatic multiple myeloma patients over time. To determine the effect of different treatment periods (1996–2000, 2001–2006 and 2007–2011) on the risk of fractures in patients with multiple myeloma. This retrospective case-control study included patients with multiple myeloma in Denmark, using the Danish National Health Service. Cases were defined as patients who had sustained a fracture between 1996 and 2011, and controls were those without a fracture. Exposure was defined as an ICD code for multiple myeloma. Vertebral fractures, gender, and age were considered in secondary analyses. Conditional logistic regression was used to estimate odd ratios (ORs) of fracture risk, and the analyses were adjusted for comorbidities and recent drug use. The study population consisted of 925,341 cases, and the same number of matched controls, of whom 1334 patients with multiple myeloma. Among cases, the risk of any fracture was higher in multiple myeloma patients compared to patients without multiple myeloma (any fracture: OR adj [95% CI] 1996–2000: 1.7[1.3–2.3]; 2001–2006: 1.3[1.1–1.6]; 2007–2011: 1.7[1.4–2.2]). Although fractures were mainly non-vertebral, the risk of vertebral fractures in particular was higher in multiple myeloma patients (vertebral fracture: OR adj [95% CI] 1996–2000: 3.5[1.4–8.6]; 2001–2006: 4.0[1.9–8.2]; 2007–2011: 3.0[1.6–5.7]). Despite new treatment strategies and improved supportive care, this study showed no decreased fracture risk for multiple myeloma patients over time. New treatment strategies, even if they have a positive impact on overall survival, offer no guarantee for a corresponding reduction in bone lesions. • No decrease in fracture risk over time was found for multiple myeloma patients. • New treatment options do not guarantee a corresponding reduction in bone lesions. • There is a strong clinical need for new bone-sparing strategies in multiple myeloma. [ABSTRACT FROM AUTHOR]

Introduction: The diagnosis aceruloplasminemia is usually made in patients with advanced neurological manifestations of the disease. In these patients prognosis is poor, disabilities are severe and patients often die young. The aim of our study was to facilitate recognition of aceruloplasminemia at a disease stage at which treatment can positively influence outcome. Currently, the neurological phenotype of aceruloplasminemia has been mainly described in Japanese patients. This 'classical' phenotype consists of cerebellar ataxia, hyperkinetic movement disorders and cognitive decline. In this study we describe the spectrum of neurological disease in Caucasian patients.Methods: Data on neurological presentation and follow-up were gathered from both our patients, homozygous for the G631R mutation in the CP gene, and other published Caucasian cases. Neurological features of aceruloplasminemia in Caucasian patients were compared to those summarized in Japanese patients.Results: 21 Caucasian patients, both ours and the described cases, displayed a wide range of movement disorders with predominant chorea, parkinsonism and ataxia, and also tremor and dystonia. In addition to cognitive decline, nearly half of the Caucasian patients presented with psychiatric changes, including depression, anxiety and behavioral changes. In one-third of the neurologically symptomatic Caucasian patients, cognitive- or psychiatric changes were the first neurological manifestations of aceruloplasminemia.Conclusions: Aceruloplasminemia in Caucasian patients can present with a wider range and a different order of neurological symptoms than previously described in Japanese patients. Psychiatric changes and parkinsonism can be added to the spectrum of neurological disease. Cognitive- or psychiatric changes may be the first neurological manifestations of aceruloplasminemia. [ABSTRACT FROM AUTHOR]

• The prognostic ability of IGHV mutational status and sex was validated in this cohort. • The markers sCD23, SPINT1, and LY9 have possible prognostic ability for EFS in CLL patients. • Patients with these marker levels above the median had a shorter EFS than those with marker levels below the median. • Unmutated IGHV patients with an sCD23 or sCD27 level above the median had the lowest EFS. Despite recent identification of several prognostic markers, there is still a need for new prognostic parameters able to predict clinical outcome in chronic lymphocytic leukemia (CLL) patients. Here, we aimed to validate the prognostic ability of known (proteomic) markers measured pretreatment and to search for new proteomic markers that might be related to treatment response in CLL. To this end, baseline serum samples of 51 CLL patients treated with chemo-immunotherapy were analyzed for 360 proteomic markers, using Olink technology. Median event-free survival (EFS) was 23 months (range: 1.25–60.9). Patients with high levels of sCD23 (>11.27, p = 0.026), sCD27 (>11.03, p = 0.04), SPINT1 (>1.6, p = 0.001), and LY9 (>8.22, p = 0.0003) had a shorter EFS than those with marker levels below the median. The effect of sCD23 on EFS differed between immunoglobulin heavy chain variable gene-mutated and unmutated patients, with the shortest EFS for unmutated CLL patients with sCD23 levels above the median. Taken together, our results validate the prognostic impact of sCD23 and highlight SPINT1 and LY9 as possible promising markers for treatment response in CLL patients. [ABSTRACT FROM AUTHOR]

Purpose The goal of this study is to identify and compare all direct costs of intravenous and subcutaneous rituximab given to patients with diffuse large B-cell lymphoma in the Netherlands. Methods Using a prospective, observational, bottom-up microcosting study, we collected primary data on the direct medical costs of the preparation, administration, and acquisition of rituximab. Drug costs and costs of drug wastage, labor costs, material costs, and outpatient costs were identified using standardized forms, structured using prices from official pricelists, and compared for the intravenous and subcutaneous forms of rituximab. Findings Measurements were taken on 53 rituximab administrations (33 intravenous and 20 subcutaneous) and on 13 rituximab preparation (7 intravenous and 6 subcutaneous). The mean total costs were €2176.77 for the intravenous infusion and €1911.09 for the subcutaneous injection. The estimated difference of €265.17 (95% CI, €231.99–`€298.35) per administration was mainly attributable to differences in time spent in the chemotherapy unit, related outpatient costs, drug wastage, and drug costs. Implications Rituximab administered in the form of subcutaneous injection is less costly than its intravenous form. With their equal effectiveness taken into account, subcutaneous rituximab administration can result in significant savings when transferred to the total diffuse large B-cell lymphoma population in the Netherlands. [ABSTRACT FROM AUTHOR]