Overall and complete response rates as potential surrogates for overall survival in relapsed/refractory multiple myeloma.

Aim: The correlation between response and survival has not been well-studied in relapsed or refractory multiple myeloma (RRMM). Materials & methods: A systematic literature review of Medline, Embase and Cochrane databases (2010-06/2020) and relevant congresses (2018-2020) was performed to identify randomized clinical trials in RRMM reporting median overall survival (mOS), progression-free survival and response end points. The relationship between mOS and response end points was analyzed using Pearson's product-moment correlation. Results: A total of 81 records for 65 original studies, representing 12,827 patients were included. The correlation was moderate for mOS with overall response rate (Pearson r = 0.79), very good partial response (r = 0.73) and duration of response (r = 0.78); all were statistically significant. In linear regression models, estimated mOS gain was 0.48, 0.47 and 1.94 months per percentage point of overall response rate, very good partial response and complete response, respectively (all p < 0.001). Significance was maintained after adjustment for age, relapsed versus refractory multiple myeloma and study year. The analysis was limited by small sample sizes and inconsistent reporting of study-level covariates. Conclusion: These findings support short-term response-based end points as surrogates to survival in RRMM.

Treatments for multiple myeloma may not work for every patient and the cancer may come back. In clinical trials, it is difficult to find out how well new treatments work in allowing patients to live longer. This is especially true when patients have advanced disease that has returned or has not responded to treatment. How well a patient responds to treatment (i.e., has a decreased extent of disease) could indicate whether the drug will help the patient live longer, but the relationship between response to treatment and survival is not fully understood. We conducted a systematic review and meta-analysis to better understand how response rates and survival are related. A systematic review collects all the published research on a specific subject, and a meta-analysis is a statistical method that creates a single finding from several separate studies. This study found a moderate relationship between how long patients live after receiving treatment for multiple myeloma and their response to treatment. This would allow response-to-treatment data from clinical trials to be used to predict better survival and show the drug can help patients.

Characterizing the Patient Journey in Multiple Myeloma: Qualitative Review.

BACKGROUND: The patient experience of multiple myeloma (MM) is multifaceted and varies substantially between individuals. Current published information on the patient perspective and treatment of MM is limited, making it difficult to gain insights into patient needs regarding the condition. OBJECTIVE: In this review, a combined research method approach (ie, the review of published literature and social media posts) was undertaken to provide insight into patients' perspectives on the burden and treatment of MM, the impact of the COVID-19 pandemic, and the impact of MM on caregivers of patients with MM. METHODS: Targeted searches of PubMed and PsycINFO were conducted from November 16, 2010, to November 16, 2020; in parallel, patient-reported information derived from social media posts from 6 patient advocacy websites and YouTube were searched. The review of patient advocacy websites and YouTube targeted patient-reported information from patients with a self-reported diagnosis of MM who discussed their experience of MM and its treatments. RESULTS: A total of 27 articles and 138 posts were included (patient-reported information included data from 76 individuals), and results from both sources showed that patients experienced a variety of symptoms and treatment side effects, including neuropathy, fatigue, nausea, and back pain. These can affect areas of health-related quality of life (HRQOL), including physical functioning; emotional, psychological, and social well-being; the ability to work; and relationships. Patients valued involvement in treatment decision-making, and both the patient-reported information and the literature indicated that efficacy and tolerability strongly influence treatment decision-making. For patients, caregivers, and physicians, the preference for treatments was strongest when associated with increased survival. Caregivers can struggle to balance care responsibilities and jobs, and their HRQOL is affected in several areas, including emotional-, role-, social-, and work-related aspects of life. The COVID-19 pandemic has challenged patients' ability to manage MM because of limited hospital access and restrictions that negatively affected their lives, psychological well-being, and HRQOL. Unmet patient needs identified in the literature and patient-reported information were for more productive appointments with health care professionals, better-tolerated therapies, and more support for themselves and their caregivers. CONCLUSIONS: The combination of published literature and patient-reported information provides valuable and rich details on patient experiences and perceptions of MM and its treatment. The data highlighted that patients' HRQOL is impeded not only by the disease but also by treatment-related side effects. Patients in the literature and patient-reported information showed a strong preference for treatments that prolong life, and patients appeared to value participation in treatment decisions. However, there remain unmet needs and areas for further research, including treatment, caregiver burden, and how to conduct appointments with health care professionals. This may help improve the understanding of the journey of patients with MM. PLAIN LANGUAGE SUMMARY: Multiple Myeloma (MM) is the second most common cancer that affects blood cells. In this study, researchers wanted to know patients' views on the effects of MM and the treatments they received. Researchers also looked at the impact of the COVID-19 pandemic on patients' treatment and the impact of MM on caregivers. To this end, the researchers reviewed information from 27 published studies and 138 social media posts by 76 patients with MM. Patients commonly reported nerve pain, tiredness, feeling sick, and back pain caused by MM and the treatments they received. The effects of MM and treatments affected patients' physical function; emotional, psychological, and social well-being; ability to work; and relationships. The researchers found that patients wanted to be involved in decisions related to their treatment. The effectiveness against MM and known negative effects strongly influenced the choice of treatments for patients. Increased survival was the strongest factor in the choice of treatment for patients, caregivers, and doctors. Researchers found that the emotional-, role-, social-, and work-related aspects of caregivers' lives were affected by caring for patients with MM. The COVID-19 pandemic also affected the ability of patients to manage their MM because of limited hospital access and the effects of restrictions that impacted their lives and psychological well-being. Finally, the researchers identified some areas requiring improvement, including unproductive appointments with health care professionals, the need for treatments with fewer negative effects, and more support for patients with MM and their caregivers. This information may be useful to improve and understand the experience of patients with MM.

Response rates and minimal residual disease outcomes as potential surrogates for progression-free survival in newly diagnosed multiple myeloma.

Progression-free survival (PFS) is a common primary endpoint in newly diagnosed multiple myeloma (NDMM). Patients with NDMM typically have longer PFS and are more likely to achieve minimal residual disease (MRD) or complete response (CR) compared to patients with relapsed or refractory multiple myeloma. Response-based surrogate endpoints may hold value given the longer follow-up time required to evaluate PFS in NDMM. In this work, systematic literature reviews of Medline, Embase, and Cochrane databases (2010-06/2020) and relevant congresses (2018-2020) were performed to identify randomized clinical trials (RCTs) and real-world studies in NDMM reporting median PFS and objective response. Associations between PFS and each response endpoint were evaluated using Pearson's product-moment correlation weighted by sample size in each RCT arm. Unadjusted and adjusted weighted linear regression models were applied to estimate the gain in median PFS associated with each response endpoint. Statistically significant correlations were identified for median PFS with overall response rate (ORR; Pearson r = 0.59), CR (r = 0.48), stringent CR (sCR; r = 0.68), and MRD (r = 0.69). The unadjusted models estimated 0.50 (95% CI: 0.36, 0.64; p<0.001), 0.42 (95% CI: 0.25, 0.58; p<0.001), 1.05 (95% CI: 0.58, 1.52; p<0.001), and 0.35 (95% CI: 0.12, 0.58; p = 0.006) months of median PFS gained per point of ORR, CR, sCR, and MRD, respectively. Associations for median PFS remained statistically significant in models adjusted for age and treatment type with ORR (0.35, 95% CI: 0.21, 0.49; p<0.001), and adjusted for age and International Staging System risk stage with CR (0.29, 95% CI: 0.16, 0.41; p<0.001). Due to small sample size, adjusted models could not be constructed for sCR or MRD. Nevertheless, evidence of significant survival benefit (p<0.05) associated with MRD negativity and sCR was identified across real-world studies. These findings provide support for the use of response outcomes as surrogate endpoints to estimate PFS benefit in NDMM.

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.

Cost Effectiveness of Gemtuzumab Ozogamicin in the First-Line Treatment of Acute Myeloid Leukaemia in the UK.

BACKGROUND AND OBJECTIVE: The phase III ALFA-0701 study demonstrated the efficacy and safety of gemtuzumab ozogamicin (GO) versus standard of care (SOC) chemotherapy (daunorubicin and cytarabine) for the treatment of adult patients with de novo CD33+ acute myeloid leukaemia (AML). This study analysed the cost-effectiveness of GO from the perspective of the UK health care payer. METHODS: A cohort state-transition model was developed to estimate direct health care costs and quality-adjusted life-years (QALYs) over a lifetime time horizon from AML diagnosis to death using monthly cycles. Data on complete remission, overall survival, relapse-free survival (RFS), haematopoietic stem-cell transplantation, and adverse events for GO plus SOC versus SOC were obtained from the ALFA-0701 study. Overall survival and RFS were extrapolated beyond the trial horizon using mixture cure models. Unit costs were obtained from standard national sources. Utilities were identified in a systematic literature review. Costs and outcomes were discounted at 3.5%. Analyses were performed for the base-case population, excluding patients with an unfavourable cytogenetic profile, and the overall population. RESULTS: For the base-case and overall populations respectively, incremental per-patient costs (£13,456 and £14,773) and QALYs (0.99 and 0.68) for GO plus SOC versus SOC resulted in incremental cost-effectiveness ratios (ICERs) of £13,561 and £21,819 per QALY gained. The mean probabilistic ICERs were £14,217 and £23,245, respectively. Univariate sensitivity analyses supported the robustness of the results. CONCLUSIONS: The ICERs for both populations met NICE's £20,000-£30,000 willingness-to-pay threshold for medicines and supported the current approval for GO.

Comparing cure rates for gemtuzumab ozogamicin plus standard chemotherapy vs standard chemotherapy alone in acute myeloid leukemia patients.

Aim: Assess the suitability of standard parametric, piecewise and mixture cure models (MCMs) for modeling long-term survival of acute myeloid leukemia patients achieving remission following treatment with gemtuzumab ozogamicin (GO) + standard chemotherapy (SC) or SC alone. MCMs can model survival data comprising of statistically cured (patients in long-term remission) and uncured patients. Materials & methods: Models were fit to patient-level data corresponding to individual treatment arms. Results: Visual inspection showed that MCMs fit the clinical data best. Survival modeling with MCMs showed that treatment with GO + SC versus SC alone results in higher statistical cure rates for event-free survival (rates: 26-35% vs 21-23%) and overall survival (rates: 48-52% vs 38-44%). Conclusion: MCMs are well suited to modeling long-term survival in acute myeloid leukemia patients. Clinical trial registration: NCT00927498 (ClinicalTrials.gov).

Lay abstract To assess the effectiveness of acute myeloid leukemia (AML) treatments, researchers use statistical models to estimate the survival rate of patients who receive a particular treatment. Some patients receiving certain AML treatments can achieve long-term remission and are often considered 'cured'. Standard statistical models cannot differentiate between cured and uncured patients and so tend to underestimate the survival rates of cured patients. Mixture cure models (MCMs) can account separately for the survival of cured versus uncured patients. We tested MCMs and standard statistical models using data from a clinical trial comparing gemtuzumab ozogamicin (GO) + standard chemotherapy against standard chemotherapy alone in AML patients. Of all the models tested, MCMs generated survival extrapolations over time that most closely resembled the data from the clinical trial. Through our analyses, we demonstrated that GO + standard chemotherapy can result in higher survival rates than standard chemotherapy alone.

An indirect comparison between bosutinib, nilotinib and dasatinib in first-line chronic phase chronic myeloid leukemia.

OBJECTIVE: Bosutinib, nilotinib and dasatinib are approved for the treatment of patients with newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML). In the absence of head-to-head comparisons between second-generation tyrosine kinase inhibitors (TKIs), the objective of this study was to indirectly compare the efficacy of bosutinib with nilotinib and dasatinib in first-line (1L) CP-CML. METHODS: Cross-trial heterogeneity in terms of patient baseline characteristics and imatinib dose escalation are difficult to adjust for in network meta-analyses and anchored matching-adjusted indirect treatment comparisons (MAICs). Therefore, an unanchored MAIC was performed using patient level data from bosutinib (BFORE trial) and published aggregated data from nilotinib (ENESTnd) and dasatinib (DASISION) trials. After matching, cytogenetic and molecular responses, and disease progression, after a minimum follow-up of 24 months were compared between nilotinib versus bosutinb and dasatinib versus bosutinib. RESULTS: The comparison of nilotinib versus bosutinib resulted in no statistically significant differences for MMR at and by 24 months, MR4 by 24 months, MR4.5 at and by 24 months, CCyR by 24 months, and disease progression, however, a decreased odds of MR4 at 24 months in favor of bosutinib versus nilotinib was observed. The comparison of dasatinib versus bosutinib by 24 months resulted in no statistically significant differences for MMR, disease progression, and CCyR, however a decreased odds of MR4.5 in favor of bosutinib versus dasatinib was observed. CONCLUSIONS: Overall, in these analyses bosutinib demonstrates equivalent efficacy to nilotinib and dasatinib in the treatment of patients with newly diagnosed CP-CML.

Budget Impact Analysis of Gemtuzumab Ozogamicin for the Treatment of CD33-Positive Acute Myeloid Leukemia.

BACKGROUND: Gemtuzumab ozogamicin (GO) was approved in 2017 in the US for the treatment of adults with newly diagnosed CD33-positive (CD33+) acute myeloid leukemia (AML), and adults and pediatric patients with CD33+ relapsed/refractory (R/R) AML. OBJECTIVE: The aim of this study was to estimate the budgetary impact of introducing GO to a 1-million-member US health plan over a 5-year period. METHODS: We developed models to estimate the impact of introducing GO in combination with conventional induction chemotherapy or as monotherapy for newly diagnosed AML, and as monotherapy for R/R AML. Models were built using data on drug costs and treatment-related outcomes obtained from published clinical trials and other publicly available sources. Results were reported on a per member/per year and per member/per month (PMPM) basis. RESULTS: Base-case results of the newly diagnosed model indicated that the addition of GO in the combination setting reduced the overall budget of a 1-million-member health plan. The estimated net cost (US$) savings ranged from $72,969 ($0.006 PMPM) in year 1 to $745,426 ($0.062 PMPM) in year 5. In the monotherapy setting, GO was associated with increased net costs ranging from $4118 (0.0003 PMPM) in year 1 to $31,885 ($0.003 PMPM) in year 5. Base-case results of the R/R AML model demonstrated increased net costs that ranged from $17,326 ($0.001 PMPM) in year 1 to $46,163 ($0.004 PMPM) in year 5. Scenario analyses in all settings indicated the budget impact was not overly sensitive to the selected input assumptions, with the exception of the scenario considering only the pharmacy budget impact in the combination setting. CONCLUSIONS: The introduction of GO for newly diagnosed and R/R AML would have a minimal impact on the budget of a US health plan and could result in cost savings in the combination therapy setting for newly diagnosed AML.

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.

Relationship between molecular response and quality of life with bosutinib or imatinib for chronic myeloid leukemia.

Patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML) can be effectively treated with tyrosine kinase inhibitors (TKIs) and achieve a lifespan similar to the general population. The success of TKIs, however, requires long-term and sometimes lifelong treatment; thus, patient-assessed health-related quality of life (HRQoL) has become an increasingly important parameter for treatment selection. Bosutinib is a TKI approved for CP CML in newly diagnosed adults and in those resistant or intolerant to prior therapy. In the Bosutinib Trial in First-Line Chronic Myelogenous Leukemia Treatment (BFORE), bosutinib demonstrated a significantly higher major molecular response rate compared with imatinib, with maintenance of HRQoL (measured by the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionnaire), after 12 months of first-line treatment. We examined relationships between molecular response (MR) and HRQoL. MR values were represented by a log-reduction scale (MRLR; a continuous variable). A repeated-measures longitudinal model was used to estimate the relationships between MRLR as a predictor and each FACT-Leu domain as an outcome. Effect sizes were calculated to determine strength of effects and allow comparisons across domains. The majority of FACT-Leu domains (with the exception of social well-being and physical well-being) demonstrated a significant relationship with MRLR (p < 0.05). Our results showed variable impact of clinical improvement on different dimensions of HRQoL. For patients who achieved MR5, emotional well-being and leukemia-specific domains showed the greatest improvement, with medium differences in effect sizes, whereas social well-being and physical well-being had the weakest relationship with MR.

A multi-item Physician Global Assessment scale to assess psoriasis disease severity: validation based on four phase III tofacitinib studies.

BACKGROUND: Several different Physician Global Assessment (PGA) versions have been used in clinical studies as a co-primary end point to evaluate psoriasis severity. Tofacitinib is an oral Janus kinase inhibitor. We performed an analysis of the PGA using data from studies of tofacitinib in moderate to severe chronic plaque psoriasis. METHODS: Data from 3641 patients with moderate to severe chronic plaque psoriasis, enrolled in one of four phase III tofacitinib studies (OPT Pivotal 1 and 2, OPT Compare and OPT Retreatment), were used to evaluate a three-item PGA scale. RESULTS: Confirmatory Factor Analyses showed that equal weighting of the three items (erythema, induration and scaling) was appropriate. The PGA demonstrated acceptable test-retest reliability (Intraclass Correlation Coefficient, 0.7) and internal consistency (Cronbach's Coefficient Alpha ≥ 0.9 at primary time points). The Clinically Important Difference was estimated as 0.55 (95% confidence interval: 0.546-0.563). Known-group validity was shown by demonstrating that PGA scores could discriminate between different degrees of disease severity. The PGA was significantly correlated with other clinical end points in the studies (Psoriasis Area and Severity Index, r = 0.75-0.79; Dermatology Life Quality Index, r = 0.44-0.57; Patient Global Assessment, r = 0.66-0.72). CONCLUSIONS: Consistent with previous findings from a phase II study, these results indicate that this PGA is a valid, reliable instrument for evaluating disease severity in clinical studies of psoriasis.

Matching-adjusted indirect comparison of bosutinib, dasatinib and nilotinib effect on survival and major cytogenetic response in treatment of second-line chronic phase chronic myeloid leukemia.

Objective: In clinical trials of second-line therapies for chronic phase chronic myeloid leukemia (CP-CML), to date, only single-arm trials have been conducted for the available tyrosine kinase inhibitor treatments (bosutinib, dasatinib and nilotinib). These trials included heterogeneous patient populations in terms of disease and baseline characteristics. These hamper the use of standard network meta-analyses for indirect treatment comparison of relative efficacy. In this situation, a matching-adjusted indirect comparison (MAIC) in second-line CP-CML was performed. The aim was to compare the relative efficacies of bosutinib, dasatinib and nilotinib in second-line CP-CML patients.Methods: The MAIC was preceded by a systematic literature review that ensured inclusion of the underlying data for the analyses. The outcomes were measured in terms of overall survival (OS), progression-free survival (PFS) and major cytogenetic response (MCyR). The treatments were quantitatively compared based on Cox proportional hazard ratio (HR) regressions, on restricted mean survival (RMST, when the proportionality assumption showed evidence of violation) and on odds ratios (for response measures).Results: Comparing with dasatinib, bosutinib resulted in HRs for PFS and OS of 0.63 (0.44-0.90, p < .05) and 0.82 (0.54-1.26, p = .37) respectively, and resulted in an OR for MCyR of 0.78 (0.53-1.16). Although the proportionality of hazards assumption was violated for PFS, the RMST analyses confirmed the findings of the Cox regression. When compared with nilotinib, bosutinib showed a significant HR of 0.54 (0.38-0.76, p < .01) in favor of bosutinib for PFS, a non-significant HR of 0.72 (0.46-1.13, p = .16) for OS and a non-significant OR of 0.98 (0.71-1.35) for MCyR.Conclusions: Bosutinib had a significantly greater PFS than both dasatinib and nilotinib. For OS, the findings were numerically in favor of bosutinib, but not statistically significant. For MCyR, the findings were numerically in favor of dasatinib and nilotinib, but not statistically significant.

Patient-reported outcomes in the phase 3 BFORE trial of bosutinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia.

BACKGROUND: In the phase 3 BFORE trial (NCT02130557), treatment with bosutinib resulted in a significantly higher major molecular response rate at 12 months versus imatinib in the modified intent-to-treat (mITT) population of patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML). Assessment of patient-reported outcomes (PROs) was an exploratory objective. METHODS: Patients with newly diagnosed CP CML were randomized 1:1 to receive once-daily bosutinib 400 mg or imatinib 400 mg as first-line therapy. Patients completed the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) and EuroQoL-5 Dimensions (EQ-5D) questionnaires at baseline, every 3 months for the first 24 months of treatment, every 6 months thereafter, and at treatment completion. We report PRO results at month 12 in the mITT population (bosutinib: n = 246; imatinib: n = 241). RESULTS: Mean FACT-Leu combined and subscale scores were similar at baseline in the bosutinib and imatinib arms; at month 12, all scores demonstrated improvement or maintenance of health-related quality of life (HRQoL) in both treatment arms. Repeated-measures mixed-effects models showed no significant difference between bosutinib and imatinib for any FACT-Leu score. Functional health status, as measured by EQ-5D, also demonstrated improvement or maintenance with bosutinib and imatinib at month 12. CONCLUSIONS: Similar improvements in PROs compared with baseline were seen after 12 months of treatment with first-line bosutinib or imatinib in the BFORE trial. Newly diagnosed patients with CP CML receiving bosutinib or imatinib can preserve or improve HRQoL during treatment, although clinical efficacy was superior with bosutinib.

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.

A comparative evaluation of gemtuzumab ozogamicin + daunorubicin-cytarabine and other treatments for newly diagnosed acute myeloid leukemia.

AIM: To evaluate the comparative efficacy and safety of gemtuzumab ozogamicin + daunorubicin-cytarabine (GO + DA) versus common induction therapies for newly diagnosed acute myeloid leukemia. Materials & methods: A network meta-analysis following a systematic literature review. RESULTS: In base-case analyses, GO + DA was associated with significantly greater overall survival and relapse-free survival versus most comparators, and similar rates of complete remission versus all evaluated comparators. Similar findings were seen in the subgroup analyses. Grade 3+ bleeding and hepatic events were higher with GO + DA versus some comparators, consistent with GO's profile. No differences were found for other evaluated outcomes. CONCLUSION: GO + DA provides significant overall survival and relapse-free survival benefit versus evaluated induction regimens for newly diagnosed acute myeloid leukemia.

Social preferences for health states associated with acute myeloid leukemia for patients undergoing treatment in the United Kingdom.

BACKGROUND: Health state (HS) utility values for patients with acute myeloid leukemia (AML), a hematological malignancy, are not available in the United Kingdom (UK). This study aims to develop clinically sound HSs for previously untreated patients with AML and to assign utility values based on preferences of the general UK population. METHODS: This study was conducted in the UK and comprised 2 stages. During the first stage, AML HSs were drafted based on evidence from a literature review of AML clinical and health-related quality-of-life studies (published January 2000-June 2016) and patient-reported outcome measures previously used in this population. A panel of UK hematologists with AML experience validated the clinical relevance and accuracy of the HSs. During the second stage, validated HSs were valued in an elicitation survey with a representative UK population sample using the time trade-off (TTO) method. Descriptive statistics and bivariate tests were obtained and performed. RESULTS: A total of eight HSs were developed and clinically validated, including treatment with chemotherapy, consolidation therapy, transplant, graft-vs-host disease (GvHD), remission, relapse, refractory, and functionally cured. In total, 125 adults participated (mean age, 49.6 years [range, 18-87 years], 52.8% female). Mean (95% confidence interval [CI]) TTO preference values (n = 120), ranked from lowest (worst HS) to highest (best HS) were as follows: refractory - 0.11 (- 0.21 to - 0.01), relapse 0.10 (0.00-0.20), transplant 0.28 (0.20-0.37), treatment with chemotherapy 0.36 (0.28-0.43), GvHD 0.43 (0.36-0.50), consolidation 0.46 (0.40-0.53), remission 0.62 (0.57-0.67), and functionally cured 0.76 (0.72-0.79). Mean (95% CI) visual analog scale preference values followed the same rank order, ranging from 0.15 (0.13-0.17) for refractory to 0.71 (0.68-0.73) for functionally cured. CONCLUSIONS: To our knowledge, this is the first study to report utility values for AML from the UK societal perspective. Participants were able to distinguish differences in severity among AML HSs, and preference values were consistent with clinical perception of HS severity. HS preference values observed in this study may be useful in future evaluations of treatment benefit, including cost-effectiveness analyses and improved patient well-being.

Validation of the Itch Severity Item as a Measurement Tool for Pruritus in Patients with Psoriasis: Results from a Phase 3 Tofacitinib Program.

Tofacitinib is an oral Janus kinase inhibitor. This post-hoc analysis aimed to investigate the psychometric properties of the Itch Severity Item (ISI), a numeric rating scale from 0 (no itching) to 10 (worst possible itching) for pruritus in psoriasis, and review the effect of tofacitinib on pruritus in patients with psoriasis participating in Phase 3 studies (N = 3,641). The ISI showed high test-retest reliability (intra-class correlation coefficient: 0.84). The clinically important difference was defined as a 1.48-point change, using Patient Global Assessment as an anchor. Mean changes from baseline in ISI scores with tofacitinib were significantly greater than placebo by Day 2 and exceeded the clinically important difference by Week 4 and Week 2 for tofacitinib 5 and 10 mg twice daily, respectively. The sound psychometric properties of the ISI as an assessment tool for pruritus in psoriasis were confirmed. Tofacitinib provided clinically meaningful improvements in psoriatic pruritus versus placebo.

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.

Initiation, Switching, and Cessation of Psoriasis Treatments Among Patients with Moderate to Severe Psoriasis in the United States.

BACKGROUND: Psoriasis patients frequently switch among multiple therapies while managing their psoriasis. Determining treatment transitions is fundamental to understanding how patients access and use treatments. OBJECTIVE: We aimed to identify patterns of treatment transitions of US patients with moderate to severe psoriasis over 5 years. METHODS: This was a retrospective, longitudinal cohort study in which US patients aged ≥18 years who had at least one psoriasis claim (International Classification of Diseases, Ninth Revision [ICD-9] diagnosis) were continuously enrolled in a health plan between October 2007 and September 2012. Data from eligible patients were projected to reflect the total US insured population with moderate to severe psoriasis, and the proportions of patients who started, stopped, switched, and restarted treatment at any time between September 2011 and September 2012 were analyzed. Treatment categories were biologics, traditional oral systemics, topicals, phototherapy, lapsed from treatment, and treatment-naive. RESULTS: There were 8.9 million patients in the claims database, of whom 0.9 million (10.4%) had a psoriasis diagnosis and 46,369 (0.5%) met the inclusion criteria. When projected, 1.7 million insured patients had moderate to severe psoriasis. Of these, an estimated 807,000 patients had lapsed treatment, an additional 346,000 were receiving treatment, and 547,000 were defined as being treatment-naive. A total of 81,000 of 346,000 patients had switched treatment in the preceding year. In addition, many patients stopped (438,000) and restarted (384,000) treatment in the 12-month period. CONCLUSION: Based on health claims data, undertreatment of moderate to severe psoriasis appeared to be common.

Under-Treatment of Patients with Moderate to Severe Psoriasis in the United States: Analysis of Medication Usage with Health Plan Data.

INTRODUCTION: Psoriasis is a chronic inflammatory disorder with significant morbidity and mortality, but a persistent gap appears to exist for the adequate treatment of patients with moderate to severe disease. As the extent of under-treatment is unknown, we attempted to determine overall treatment patterns and estimate under-treatment using a large database. METHODS: Data from the US National Health and Wellness Survey was used to estimate the proportion of patients with mild, moderate or severe psoriasis. The proportion with moderate to severe disease was estimated by excluding those with mild disease, and projecting this to the total insured US population, weighted by age and gender. Using US health plan claims data, patient totals by treatment type were determined between October 1, 2007 and September 30, 2012. Patients had to be continuously enrolled in a health plan and be ≥18 years at the end of the analysis window. Psoriasis was confirmed if patients had at least one claim of any type of psoriasis except psoriatic arthropathy (ICD-9 code 696.1). A monthly treatment history, classified by biologic, traditional oral systemic, phototherapy and topical therapy, was recorded for each patient. RESULTS: There were an estimated 1.7 million insured US patients with moderate to severe psoriasis. Of these, 1 million (59%) were not treated for their condition in the preceding year. Among 695,488 patients who were treated for psoriasis in the preceding year, 346,201 were currently receiving treatment and 349,287 had lapsed treatment. Of the patients lapsed and currently treated in this period, the numbers who received each treatment type were 156,409 (biologic), 222,657 (traditional oral systemic), 22,911 (phototherapy), and 293,511 (topical). A limitation of the study was that only insurance claims were analyzed. CONCLUSION: Moderate to severe psoriasis remains persistently untreated or under-treated. We suggest that potential barriers preventing access to care be explored. FUNDING: This study was sponsored by Pfizer Inc.