Efficacy of non-intensive therapies approved for relapsed/refractory acute myeloid leukemia: a systematic literature review.

Aim: De novo relapsed and/or refractory acute myeloid leukemia (rrAML) has limited treatment options for patients not eligible ('unfit') to receive intensive chemotherapy-based interventions. The authors aimed to summarize outcomes for licensed therapies in this setting. Materials & methods: A systematic literature review identified licensed therapies in this setting. A feasibility assessment was made to conduct a network meta-analysis to evaluate comparative efficacy. Results: Seven unique trials were identified. Median survival months were 13.8 for gemtuzumab ozogamicin (GO), 9.3 for gilteritinib (FLT3 mutated rrAML), 5.6 for low-dose cytarabine and 3.2 for best supportive care; transplant rates with gilteritinib and GO were 25.5 and 19%, respectively. A network meta-analysis was not feasible. Conclusion: There remains a high unmet need in de novo rrAML patients not eligible for intensive therapy, with GO and gilteritinib (only FLT3-mutated AML) providing the best current options.

Some patients with acute myeloid leukemia (AML) have no response to initial treatment or have a response that is subsequently lost. Follow-on treatment options after that initial stage are limited, especially for patients who are not able to have intensive therapy, such as chemotherapy, due to age, physical or cognitive function, existing comorbidities or symptoms. This study aimed to review the published literature to identify data associated with treatments that are licensed for use in patients ineligible for intensive therapy who do not maintain a response from their initial therapy. The study found that the drug gilteritinib was an option for the subgroup of AML patients with FLT3-mutated disease with an average life expectancy just under 1 year, while gemtuzumab ozogamicin was an option for a wider group of AML patients with a life expectancy just over 1 year. Between a fifth and a quarter of patients went on to receive a stem-cell transplant after treatment with one of these. With limited options, this patient group needs further attention; however, the availability of the previously mentioned treatments is promising.

Humanistic and Economic Burden of Non-Muscle Invasive Bladder Cancer: Results of Two Systematic Literature Reviews.

PURPOSE: Non-muscle invasive bladder cancer (NMIBC) is a malignancy restricted to the inner lining of the bladder. Intravesical Bacillus Calmette-Guerin (BCG) following transurethral resection of the bladder tumor is the mainstay first-line treatment for high-risk NMIBC patients. Two systematic literature reviews (SLRs) were conducted to further assess the current evidence on BCG use in NMIBC and the humanistic and economic burden of disease. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, Embase® and MEDLINE® were searched using the Ovid platform to identify interventional or real-world evidence studies on the health-related quality of life (HRQoL) and economic burden in NMIBC. Limited evidence was found from initial economic SLR searches in NMIBC, so additional targeted searches for bladder cancer were conducted to expand findings. RESULTS: Fifty-nine publications were included in the HRQoL SLR, of which 23 reported HRQoL and symptoms in NMIBC. At diagnosis, HRQoL was comparable with population norms but worsened considerably 2 years following diagnosis. Maintenance therapy with intravesical BCG was associated with reduced HRQoL, and treatment-related adverse events (AEs) resembled typical NMIBC symptoms. Twenty-two studies reported decreasing BCG compliance over time. Common AEs with BCG were frequent urination, lower urinary tract symptoms, pain, and hematuria. Forty-two publications were included in the economic SLR, of which nine assessed healthcare costs and resource use in NMIBC or bladder cancer. High-risk disease and high-intensity treatment were associated with increased healthcare costs. CONCLUSION: NMIBC has a considerable symptomatic, HRQoL, and economic burden. Symptoms persisted and HRQoL worsened despite intravesical BCG treatment. NMIBC is a costly disease, with higher healthcare costs associated with increased risk of disease progression and recurrence. There is a high unmet need for safe and effective treatments that reduce the risk of disease progression and recurrence, provide symptomatic relief, and improve HRQoL for patients.

A real-world, cross-sectional, community survey of symptoms and health-related quality of life of adults with acute myeloid leukemia.

Aim: We used Adelphi Real World Disease-Specific Programme data to characterize adults with newly diagnosed or relapsed/refractory de novo acute myeloid leukemia (AML). Materials & methods: Community-practice hematologists/oncologists completed patient record forms for their regular AML patients. Patients were invited to complete patient self-completion forms including 3-Level EuroQol 5-Dimensions (EQ-5D-3L) and Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionnaires. Results: Physicians provided patient record forms for 389 patients (339 newly diagnosed, 50 relapsed/refractory); 68 patients completed patient self-completion forms. Mean EQ-5D visual-analog scale and index and FACT-General scores were significantly lower than US population norms (p < 0.0001); health-related quality of life (HRQoL) scores were generally lower than 11 other cancers. Conclusion: HRQoL impairment is grave in AML. Efforts are needed to improve HRQoL in affected patients.

Long-term patient-reported outcomes from an open-label safety and efficacy study of bosutinib in Philadelphia chromosome-positive chronic myeloid leukemia patients resistant or intolerant to prior therapy.

BACKGROUND: Health-related quality of life (HRQOL) in patients with chronic-phase chronic myeloid leukemia (CML) is important because of the requirement for long-term treatment. This study assessed HRQOL in bosutinib-treated patients with Philadelphia chromosome-positive CML and resistance or intolerance to 1 (chronic-phase second-line [CP2L]) or more (chronic-phase third-line [CP3L]) tyrosine kinase inhibitors who had 264 weeks or more of follow-up (ClinicalTrials.gov identifier NCT00261846). METHODS: Patient-reported HRQOL was assessed with the EuroQol 5-Dimensions Questionnaire (EQ-5D) and the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu). RESULTS: In total, 284 and 119 patients composed the CP2L and CP3L cohorts, respectively. At treatment completion, more than 50% of the patients in the CP2L and CP3L cohorts completed the EQ-5D and FACT-Leu assessments. The EQ-5D and EQ-5D visual analog scale scores were stable in both cohorts throughout treatment. The mean FACT-Leu scores were generally stable over time but were lower in magnitude in the CP3L cohort versus the CP2L cohort. The FACT-Leu scale scores of a subset of patients with chronic diarrhea (CP2L, n = 101; CP3L, n = 30) were similar to the scores of the larger cohorts. Minimally important differences (MIDs) from baseline for the FACT-Leu scale scores were observed for the following: emotional well-being (EWB), Functional Assessment of Cancer Therapy-General (FACT-G) Total, FACT-Leu Total, and Functional Assessment of Cancer Therapy Trial Outcome Index (FACT-TOI) in the CP2L cohort and FACT-Leu Total in the CP3L cohort. Among patients with chronic diarrhea, MIDs were observed for EWB, FACT-G Total, FACT-Leu Total, and FACT-TOI in the CP2L cohort and for EWB, FACT-G Total, and FACT-Leu Total in the CP3L cohort. CONCLUSIONS: HRQOL was maintained with long-term bosutinib treatment for patients with CP2L and CP3L CML. Cancer 2018;124:587-95. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Application of the Itch Severity Score in patients with moderate-to-severe plaque psoriasis: Clinically important difference and responder analyses.

The Itch Severity Score (ISS), a 0-10 numeric rating scale, was used to assess pruritus due to psoriasis in a Phase 2 b trial of tofacitinib, a novel oral Janus kinase inhibitor. 197 patients with moderate-to-severe plaque psoriasis were randomized to tofacitinib 2, 5 or 15 mg twice daily, or placebo. The ISS was recorded daily from baseline to week 2 and at study visits. Following good and recommended research practice, we performed analyses to examine the clinically important differences (CID) (between-group difference or within-group difference) and clinically important responders (CIR) (within-patient change) for the ISS. The CID and CIR were defined using Patient Global Assessment of psoriasis as an anchor and were estimated with a longitudinal model. A CID on the ISS was 1.64 and, by day 10, the mean changes from baseline in ISS values for the tofacitinib doses (placebo-adjusted) exceeded CID. A CIR on the ISS was a 30% improvement from baseline and, at week 12, 87.2% to 100% of patients receiving tofacitinib reached ≥30% improvement versus 29.4% of patients receiving placebo (p < 0.0001). Overall, the CID and CIR analyses play vital roles in the interpretation of the treatment effects measured by ISS.

Effect of Biologic Agents on Non-PASI Outcomes in Moderate-to-Severe Plaque Psoriasis: Systematic Review and Meta-Analyses.

INTRODUCTION: The objective of this review was to conduct a systematic review with meta-analysis and Bayesian mixed treatment comparisons (MTC) evaluating the impact of biologics on non-Psoriasis Area and Severity Index (PASI) health outcomes in patients with moderate-to-severe plaque psoriasis. METHODS: MEDLINE and Cochrane Central Register of Controlled Trials were searched from 1966 to May 2009. Citations were screened for randomized, controlled trials of biologics versus either placebo or each other in adults with moderate-to-severe plaque psoriasis and reported any of several outcomes. Traditional and Bayesian MTC meta-analyses were conducted for each endpoint using either a random- or fixed-effect model where appropriate. RESULTS: Thirty-eight studies met eligibility criteria. All biologics showed significant improvement in achieving a good response on the static physician's global assessment (PGA) versus placebo while, in the MTC, differences were noted between individual drugs. In achieving a good response on the dynamic PGA, all biologics showed significant improvements over placebo, while the MTC showed significant improvements with the anti-interleukins versus anti-T cells. Relative to placebo, antitumor necrosis factor (TNF) agents and anti-interleukins showed significant improvements in the Dermatology Life Quality Index (DLQI). Compared with placebo, the anti-TNF agents showed significant improvements in both 36-item Medical Outcomes Study Short-Form General Health Survey (SF-36) mental and physical component scores, while anti-T cell agents showed no improvements. The MTC showed no differences between any biologics for either the DLQI or SF-36. CONCLUSION: Individual biologics and classes showed consistent benefits across non-PASI health outcomes in patients with moderate-to-severe plaque psoriasis while MTC meta-analyses suggested that some differences exist.

Reaching patterns across working space: the effects of handedness, task demands, and comfort levels.

Two experiments are reported which examine skill demands, location, and perceived comfort levels for a preferential reaching test with left- and right-handed participants. In Experiment 1, the effect of task demands was examined by having participants perform tasks of varying difficulty with tools (Lift, Pantomime, and Use) that were placed in an array in working space. Preferred hand reaches predominated at the midline and ipsilateral positions, and decreased significantly for contralateral positions, where the frequency of preferred hand reaches increased with task difficulty. In Experiment 2 we developed a new measure (the Comfort Rating Scale) to rate the subjective feeling of comfort for reaching movements. Using the same array of tools and tasks, participants were instructed which hand to use to perform reaching movements, and then rated how the movement felt. The preferred hand was always rated as being comfortable, whereas the non-preferred hand was sensitive to the effects of task demands and tool position. The ratings showed that it was the level of comfort with the non-preferred hand, rather than with the preferred hand, that contributed to the patterns seen on the first study. The Comfort Rating Scale provides new insight into the distribution of reaching movements within working space.

The performance of left-handed participants on a preferential reaching test.

Previous research in our laboratory has examined the distribution of preferred hand (PH) reaches in working space with right-handed participants. In one study, we examined the effects of tool position and task demands on the frequency of PH reaches with right-handers (Mamolo, Roy, Bryden, & Rohr, 2004). We found that PH reaches were at a maximum within ipsilateral space, and predominated within contralateral space. This was mediated by the task demands, as shown by an increased frequency of PH reaches for the more skill demanding tasks. In the current study, we tested left-handed participants on the same procedure. Five different tools were placed in an array in front of the participant, who was required to reach for, and perform one of three tasks with the tool: Lift the tool; lift and Pantomime its use; or lift and Use the tool on its corresponding object. The results showed that PH reaches were at a maximum within ipsilateral space for all three tasks. Significantly fewer PH reaches were made for tools in contralateral space. In particular, almost no PH reaches were made for the Lift task at the most extreme contralateral position. This indicates the willingness of left-handers to use their non-preferred (i.e., right) hand. One possible explanation supported by these results is that left-handers have adapted to an environment designed for right-handers.

The effects of skill demands and object position on the distribution of preferred hand reaches.

Performance-based measures of hand preference have been developed as an objective method of examining handedness. Previous research using this method showed that both skill demands and the position of the object in working space affect preferential hand reaching. Specifically, preferred hand reaches predominated in left hemispace, in spite of the biomechanical inefficiency involved in reaching across the body midline. This was mediated by the skill demands, with a higher frequency of preferred hand reaches for tasks requiring more skill. To further examine this issue, we increased the task skill demands. Twenty-two right-handed adults reached for five tools located in an array of five positions in front of them. Participants were required to pick up the tool, pick up and demonstrate how to use it, or pick up and actually use the tool on the materials provided. The results showed that the frequency of right hand reaches was greatest for the tool use condition. This effect was mediated by the position of the object in hemispace, with more right hand reaches occurring for the Use task in left hemispace than the other tasks, in support of our previous work.