Objective Treatment options for relapsed/refractory multiple myeloma (RRMM) have expanded, but clinical burden remains high, particularly for heavily pretreated patients. This systematic literature review and meta-analysis was conducted to synthesize outcomes from clinical trials evaluating fourth line or higher (4L+) treatment regimens. Methodology Searches using Embase, MEDLINE, and CENTRAL were conducted (January 2012-March 2024), and publications from key conferences were hand-searched. Eligible studies were clinical trials that included the phase 2 dose of a National Comprehensive Cancer Network recommended intervention and whose population was ≥80% 4L+. Meta-analyses were conducted to synthesize outcomes by treatment class (CAR T-cell therapies [CAR T], bispecific antibodies [BsAb], and Other) using random effects models where possible. For outcomes where Kaplan-Meier curves were available, meta-analyses were conducted using survival function parameters fitted to each curve. Results The meta-analysis included 34 trials (5 CAR T, 3 BsAb, and 26 Other). All CAR T and 2 BsAb trials investigated BCMA-targeting interventions. The estimated overall response rates for CAR T, BsAb, and Other were 85.5% (95% confidence interval: 72.7, 92.9), 67.6% (62.0, 72.8), and 40.5% (33.3, 48.1), respectively. The 1-year overall survival was 84.4% (79.1, 88.4) for CAR T, 70.4% (66.6, 73.9) for BsAb, and 59.5% (55.8, 63.1) for Other. The 1-year progression-free survival was 59.0% (53.7, 64.0) for CAR T, 48.4% (44.2, 52.3) for BsAb, and 20.9% (17.9, 24.0) for Other. Infections occurred in 67.1% (59.6, 73.8) with CAR T, 69.2% (60.9, 76.5) with BsAb, and 60.2% (48.6, 70.9) with Other. For adverse events specific to the immune effector cell therapies of CAR T and BsAb, overall neurotoxicity occurred in 18.8% (10.0, 32.3) and 10.2% (7.2, 14.2), respectively, and cytokine release syndrome (CRS) in 92.3% (85.2, 96.2) and 71.4% (63.4, 78.3). Additional outcomes data will be presented. Conclusions This study offers a comprehensive and up-to-date synthesis of clinical trial outcomes for recommended interventions in 4L+ treatments for RRMM. While efficacy outcomes are improving with more recently approved interventions, there remains an unmet need for durable treatments with an improved safety profile in this population.

Abstract Background Patients with peanut allergy (PA) experience significant burden of illness, which impacts health‐related quality of life (HRQoL), particularly in adolescence. There is a paucity of research evaluating drivers of HRQoL scores. Methods A prospective, online survey of adolescents with self‐reported, provider‐diagnosed PA completed from November 2018 to January 2019 was used to explore drivers of the real‐world impact of PA on HRQoL using the Pediatric Quality of Life Inventory 4.0 (PedsQL) and other measures. Univariate and multivariate analyses were used to identify potential factors associated with PedsQL scores and to understand the level of association. Results A total of 102 adolescents were included. The final model included 10 variables: race, reported strict peanut avoidance, satisfaction with prophylaxis, moderate‐to‐severe reaction within the past 12 months, touching peanut as cause of most severe reaction, fear of reaction, age, gender, comorbidities, and daily life limitations. In total, three items were shown to be strong predictors of the PedsQL total score including cause of severe reaction was touching peanut (yes), level of agreement with avoiding peanut (completely agree), and satisfaction with prophylaxis (not very much/not at all). Conclusions There is substantial heterogeneity in the impact of the burden of PA on PedsQL scores across patients. This indicates the importance of shared and individualized decision making for PA management to optimize outcomes and improve HRQoL.

BACKGROUND:Peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) is the first oral immunotherapy indicated for children aged 4 to 17 years with peanut allergy. There are limited real-world data on patients treated with PTAH.OBJECTIVE:To characterize pediatric patients treated with PTAH and associated treatment patterns in US clinical practice.METHODS:US-based physicians with allergy and immunology training treating patients with peanut allergy aged 4 to 17 years with PTAH were recruited from an existing physician panel and completed an online case report form (October to December 2021) with data abstracted from patient medical charts. Physician practice circumstances, patient characteristics, and PTAH treatment patterns were reported. Time to reach the 300-mg dose and treatment persistence were assessed using Kaplan-Meier analysis.RESULTS:A geographically balanced sample of 43 physicians contributed data for 118 demographically diverse pediatric patients. Patients had heterogeneous diagnostic test results, with a wide range of peanut-specific immunoglobulin E levels; 6.8% received an oral food challenge. During the updosing phase, there were no temporary interruptions and 5.1% of the patients required downdosing. Patients reached the 300-mg dose at a median of 21.3 weeks post-initiation. The rate of PTAH persistence at 24 weeks was 93.4%. Only 1 patient discontinued treatment because of treatment-related systemic allergic symptoms, and the remaining discontinuations were for reasons other than treatment-related symptoms. Prophylactic antihistamines were used by 33.9% of the patients to prevent PTAH adverse effects.CONCLUSION:PTAH was prescribed in demographically diverse patients with a wide range of peanut-specific immunoglobulin E levels. Treatment persistence with PTAH was high in this study population, with a small number of patients experiencing treatment modification.

Abstract Objective This research sought to explore health care providers’ (HCPs) experiences of delivering the first US Food and Drug Administration (FDA) and European Commission (EC) approved peanut oral immunotherapy (peanut OIT; Palforzia). Semi-structured qualitative interviews with HCPs who had initiated treatment with ≥ 3 patients in the first nine months following FDA approval sought to identify challenges faced and successful implementation strategies. Results Eight allergists and three nurse practitioners from eight sites based in the United States participated. The HCPs included in this research were motivated to implement this novel treatment, however, entered the process with some reservations. HCPs described how successful implementation of peanut OIT requires them to be thoughtful about their clinic’s abilities to integrate complex, time-consuming treatments into their daily practice. Prior experience of OIT was deemed beneficial, but not essential for implementation and learning from others’ experience was suggested as a way of helping new prescribers overcome perceived and actual implementation challenges. Delivering licensed peanut OIT during the COVID-19 pandemic posed both challenges and unexpected opportunities for implementation. The experiences described have the potential to benefit the wider allergy community by providing practical solutions, successful implementation strategies and opportunities to enhance training and resources.

Introduction In 2020, the US Food and Drug Administration approved the first oral immunotherapy Peanut (Arachis hypogaea) Allergen Powder-dnfp (PTAH) for the mitigation of allergic reactions to peanut. Treatment involves an initial dose escalation appointment followed by ‘up-dosing' appointments at ≥2-week intervals for approximately 6 months. Daily dosing at home is required, and patients remain on long-term daily maintenance treatment. This study sought to understand patient and caregiver experiences of treatment in a real-world setting. Methods Semi-structured qualitative interviews were conducted with patients (8-17 years at treatment initiation) and caregivers of patients (4-17 years at treatment initiation). Interviews were conducted via teleconference, recorded, transcribed verbatim, and analysed using content and thematic analysis. Participants provided informed consent; the study received ethical approval from WCG Institutional Review Board. Results 13 patients and 14 caregivers at varying treatment phases (initial dose escalation, up-dosing, maintenance) participated. Experiences were characterised by four themes: 1. Preparing for treatment (e.g., information seeking), 2. Treatment in the clinic (e.g., scheduling, attending appointments), 3. Home-dosing (e.g., treatment restrictions, changes to routines), 4. Methods to successfully integrate treatment into daily lives (e.g., managing taste, establishing new routines). Despite these considerations, many participants described how actual and anticipated treatment benefits outweighed the potential burden. Conclusion Findings characterize the experience of PTAH in a real-world setting, and the benefits appear to mitigate challenges that arise from the treatment. The experiences described in this research may benefit those considering treatment by providing practical and logistical solutions for integration of treatment into daily life.

Peanut (Arachis hypogaea) Allergen Powder-dnfp (PTAH), a novel oral immunotherapy (OIT), is indicated in children (4-17) with peanut allergy (PA) to mitigate allergic reactions in conjunction with peanut-avoidant diet.

The Peanut Allergy Burden Study (PABS) assessed the real-world burden of peanut allergy (PA), including Health-Related Quality of Life (HRQoL), on patients and caregivers in the United States.

In January 2020, Peanut (Arachis hypogaea) Allergen Powder-dnfp (PTAH) became the first treatment for Peanut Allergy (PA) approved by the US Food and Drug Administration (FDA). The adoption of innovative new therapies requires consideration of the skills, logistics and practicalities required for implementation.

Background: Peanut allergy (PA) places significant burden on peanut-allergic individuals and their families, yet limited research in the United States has quantitatively examined the impact on peanut-allergic individuals and their families’ health-related quality of life (HRQoL). The Peanut Allergy Burden Study (PABS) aimed to quantify the impact of PA on the general and disease-specific HRQoL of children, adolescents, and adults with PA, as well as caregivers of children with PA. Methods: A cross-sectional survey design was employed to examine the real-world impact of PA in children, adolescents, and adults with PA, and caregivers of children with PA. Results: Of 153 adult patients, 102 adolescents, and 382 caregivers of peanut-allergic children (n = 382), 6.8% and 24.8% of participants indicated being dissatisfied or somewhat dissatisfied, respectively, with current approaches to avoid or prevent PA reactions. Approximately two-thirds of patients and caregivers indicated that PA interferes at least somewhat with daily living. In terms of general HRQoL, adolescents, adult patients, and caregivers indicated that mental/psychosocial health was more problematic than physical health. PA patients and caregivers indicated worse HRQoL in all domains compared to healthy samples, and worse overall HRQoL, psychosocial, emotional, and social functioning than a sample of chronically ill patients. Results from the allergy-specific HRQoL measures showed that adolescents experienced greater impairment in overall HRQoL due to PA and in allergen avoidance and dietary restriction than adults. Conclusion: PA negatively affects the general and PA-specific HRQoL of both patients and caregivers. The high emotional and psychosocial burden, in particular, demonstrates significant unmet need for patients with PA and their caregivers. Future work on treatment and preventive options to improve HRQoL for PA patients, particularly adolescents and their families, is needed.

The phase 3 trial PALISADE, comparing peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) oral immunotherapy versus placebo in peanut-allergic children, reported that a significantly higher percentage of PTAH-treated participants tolerated higher doses of peanut protein after 1 year of treatment. This study used PALISADE data to estimate the reduction in the risk of systemic allergic reaction (SAR) after accidental exposure following 1 year of PTAH treatment. Participants (aged 4–17 years) enrolled in PALISADE were included. Parametric interval-censoring survival analysis with the maximum likelihood estimation was used to construct a real-world distribution of peanut protein exposure using lifetime SAR history and highest tolerated dose (HTD) from a double-blind, placebo-controlled food challenge conducted at baseline. The SAR risk reduction was extrapolated using the exposure distribution and the HTD were collected at baseline and trial exit for PTAH- and placebo-treated participants. Assuming a maximum peanut protein intake of 1500 mg, participants were estimated to have < 1% probability of ingesting > 0.01 mg during daily life. The mean annual SAR risk at trial entry was 9.25–9.98%. At trial exit, the relative SAR risk reduction following accidental exposure was 94.9% for PTAH versus 6.4% for placebo. For PTAH-treated participants with exit HTD of 600 or 1000 mg without dose-limiting symptoms, the SAR risk reduction increased to 97.2%. The result was consistent in the sensitivity analysis across different parametric distributions. Oral immunotherapy with PTAH is expected to result in a substantially greater reduction in risk of SAR following accidental exposure compared to placebo among children with peanut allergy.

AR101 is an investigational oral immunotherapy (OIT) for the treatment of peanut allergy. Results from the phase III PALISADE trial demonstrated that a significantly higher percentage of AR101-treated subjects tolerated higher doses of peanut protein after one year of therapy compared to placebo. However, the benefit of AR101 in reducing anaphylactic reaction (AR) risk after accidental exposure has not been studied. This study aimed to estimate the reduction in accidental exposure related AR risk associated with AR101 using PALISADE data. Parametric interval-censoring survival analysis with maximum likelihood estimation was used to construct a real-world distribution of peanut protein exposure using baseline AR history and maximum tolerated dose (MTD) from a double-blind, placebo-controlled food challenge. The AR risk reduction was estimated using exposure distribution, and MTD assessed at both baseline and trial exit for AR101- and placebo-treated subjects, respectively. Among those who completed the PALISADE trial, the estimated reduction of accidental exposure related AR risk was 94.9% for AR101 and 6.4% for placebo. For AR101-treated subjects who achieved the primary endpoint of 600 mg MTD or higher, the associated AR risk reduction was 97.2%. The results were consistent across different parametric distribution assumptions. OIT with AR101 resulted in a significantly higher reduction in AR risk related to accidental exposure compared to placebo. In contrast to previous analyses that used unintended allergen residue from packaged food as the peanut intake assumption, this approach more closely reflects the real-world dietary experience of patients practicing peanut avoidance and thus provides a more appropriate estimate of treatment benefit.

The Peanut Allergy Burden Study (PABS) assessed the real-world burden of peanut allergy (PA) on patients and caregivers in the United States. Adolescents 13-17-years-old and caregivers of adolescents 13-17-years-old with self-reported, provider-diagnosed PA participated in PABS online survey. Medical and treatment history and the validated, age-appropriate Food Allergy Quality of Life Questionnaire (FAQLQ–Teenager Form or –Parent Form for Teenagers; 1=no issue, 7=extreme issue) were collected. Between-group analyses were conducted (chi square; t-tests). Adolescents (n=102) and caregivers of adolescents (n=94) completed PABS. Key demographic and disease history variables among adolescents (self-report versus proxy-report) were similar. Adolescents reported significantly greater burden, versus caregivers, regarding limitations that PA placed on their day-to-day life, fear of a reaction impacting emotional well-being, and greater care in avoiding direct contact with peanuts. Adolescents had higher scores (poorer quality of life [QoL]) on the FAQLQ Emotional scale compared with caregiver assessment (mean 5.07 versus 4.21, Δ>0.5 minimal clinically important difference). Adolescents and caregivers also differed significantly on the most concerning aspects of PA, with adolescents expressing more concern regarding physical symptoms during a reaction and the impact of PA on family, compared with caregivers of adolescents. PABS responses of adolescents with PA and caregivers for the adolescents under their care were similar in many respects. However, where differences were found, adolescents reported poorer QoL (impact on day-to-day life, emotional well-being, FAQLQ Emotional scale), greater concern regarding physical symptoms of reaction and impact on family, and greater care in avoiding exposure to peanuts than did caregivers.

The Peanut Allergy Burden Study (PABS) assessed the real-world burden of peanut allergy (PA) on patients and caregivers in the United States. Adolescents 13-17-years-old with self-reported, provider-diagnosed PA participated in the PABS online survey. Medical and treatment history and the validated Pediatric Quality of Life Inventory PedsQL (scores 0-100, higher is better) were collected. Between-group analyses were conducted (chi square; t-test). Adolescents with PA (n=102) completed PABS; mean±SD age was 14.7±1.4 years, 55.9% were male, 62.8% were white. The mean PedsQL Total score was 48.8; mean subscale scores were: Physical (53.6), Emotional (43.0), Social (48.2), School (46.0), and Psychosocial (44.5). These scores were significantly below the scale scores from a general population of 8-16-year-olds (n>5900; range: 78.2-87.0) and exceeded the minimum clinically important difference (4.36-9.12 points). Adolescents experiencing ≥1 PA-related reaction in the past year had significantly lower PedsQL Total score (p=0.008), as did those receiving clinician intervention for ≥1 PA reaction in the past year (p<0.001), those "not at all" to "somewhat satisfied" with current approaches to PA reaction prevention (p=0.012), those saying PA limited their day-to-day life "somewhat" to "completely" (p=0.013), or who reported a "great" to "100% chance" of not effectively dealing with a reaction (p<0.001). Adolescents with PA have substantially lower PedsQL scores than the general population of similarly aged individuals. PedsQL Total scores were significantly different between subgroups defined by recent allergic reaction/need for clinician intervention, satisfaction with reaction prevention, perceived limitations on day-to-day life, and concern about their ability to deal with a reaction.

New allergy desensitization treatments being developed offer the potential for reductions in risk of severe allergic reactions to accidental peanut exposures. This study aimed to quantify treatment features and decision-maker characteristics that influence stated preferences for desensitization treatment among caregivers of peanut-allergic children in the United States. A national sample of 500 parents completed an online discrete-choice-experiment survey. Respondents evaluated a series of two hypothetical treatment profiles alongside a no-treatment option. Treatment profiles varied in mode of administration, peanut tolerance level, proportion discontinuing treatment due to side effects, and cost. A probit model estimated probability of choosing treatment at least once out of 12 questions, as compared to never choosing treatment. A latent-class model estimated relative-importance weights for treatment features. Approximately 90% chose treatment at least once. Fathers, non-Asians, and younger parents were more likely to choose treatment at least once. Meanwhile, those who reported 100% chance of being able to manage an allergic reaction, those who perceived capsule as ‘very inconvenient’, and those who reported cost as being most important were more likely never to choose treatment. Among the 90% who chose treatment at least once, latent-class analysis identified 3 classes, representing 41%, 33%, and 27% of the sample, respectively. If offered a treatment with the mean value for efficacy, side effects, and cost, the model predicted that 8%, 70%, and 4% would choose treatment for each class, respectively. If offered the best efficacy, no side effects, and lowest cost, the model predicted that 2/3, all, and about half would choose treatment, respectively. Factors affecting likelihood to select peanut-allergy desensitization treatment were heterogeneous among caregivers participating in a choice-experiment study. Understanding the factors affecting likelihood to start desensitization treatment will be important for shared decision making between clinicians and caregivers.

The Peanut Allergy Burden Study (PABS) assessed the real-world burden of peanut allergy (PA) on patients and caregivers in the United States. Adolescents 13-17-years-old with self-reported, provider-diagnosed PA participated in the PABS online survey. Medical and treatment history and the validated Food Allergy Quality of Life Questionnaire-Teen Form (FAQLQ-TF; 1=no issue, 7=extreme issue) were collected. The relationship of the FAQLQ-TF to other measures was explored using two-tailed tests (Pearson's correlation). Adolescents with PA (n=102) completed PABS; mean±SD age was 14.7±1.4 years, 55.9% were male, and 62.8% were white. A number of variables were statistically significant correlates of FAQLQ-TF Total score: psychosocial variables, including impact of fear of a reaction on emotional well-being (p<0.001), daily life limitations (p<0.001), worry regarding epinephrine autoinjector access (p<0.001), confidence managing a reaction (p=0.025), total number of uses of advanced interventions (ER, hospital, IV epinephrine, or intubation) in their lifetime (p=0.003), and severity of their most severe reaction (p=0.006). There were no statistically significant correlations with age, sex, number of other food allergies and other health conditions, time since most recent reaction and since the most severe reaction, the lifetime number of moderate/severe reactions, and the number of reactions in the last year. These data suggest that psychosocial variables and the need to modify daily activities to practice avoidance, and a history of needing to seek advanced treatment due to exposure, are associated with a decreased disease-specific quality of life (QoL). Additional treatments for PA that may improve the QoL in peanut-allergic adolescents should be investigated.

Background: Evaluations of public health campaigns demonstrate that stroke symptom knowledge is necessary but not sufficient for timely patient activation of emergency services in acute stroke. Incorporating behavioral and psychological factors into stroke preparedness interventions may reduce pre-hospital delay. Methods: We developed and tested the feasibility of patient-based educational interventions “Control Stroke” (CS) and CS plus self-affirmation, in two pharmacies. The interventions drew on theory and methods in psychology and behavioral science, including self-affirmation and self-regulation theories. We enrolled 50 higher risk subjects, defined as age > 50 and having prescriptions for at least two drugs across 7 stroke-associated conditions. Consecutive patients were randomized to receive the (CS) intervention or CS plus self -affirmation, a strategy that reduces defensive message processing. Using a survey, we measured satisfaction with the intervention, openness to its message, self-efficacy, and knowledge of stroke symptoms immediately post-intervention and at 1 month. Results: We recruited 28 female and 22 male subjects over eight weeks. 86% of participants completed the 1-month survey. 45% of subjects were over 75 years old. CS took 10-15 minutes to complete. Satisfaction with the intervention was high: mean net promoter score was 8.9 (of 10) (CI 8.4,9.5); 96% (CI 86,99) were satisfied or completely satisfied with the program; 96% (CI 86,99) felt the session was useful, and 100% reported the information was clear and easy to understand. Stroke symptom knowledge on the validated Stroke Action Test was comparable to other stroke education studies. There was a trend towards persistence of some program benefits in the one month follow up in the CS + self-affirmation group. Conclusion: It was feasible to recruit community pharmacy subjects to participate in a brief educational intervention for stroke. Participants reported high likelihood to recommend, easy to understand content, and symptom knowledge comparable to other studies. Self-affirmation showed evidence of prolonging some benefits. Future work will validate this in a larger population intervention and measure impact in simulated stroke scenarios.

The clinical course of Crohn’s disease (CD) and the effect of its treatment are monitored through patient-reported signs and symptoms (S&S), and endoscopic evidence of inflammation. The Crohn’s Disease Patient-reported Outcomes Signs and Symptoms (CD-PRO/SS) measure was developed to standardize the quantification of gastrointestinal S&S of CD through direct report from patient ratings.

Patient-reported outcomes (PROS), which provide a direct measure of a patient's health status or treatment preferences, represent a key component of the shift toward patient-centered health care. PROs can measure the state of a patient's disease-specific and overall health throughout the care continuum, enabling them to have a variety of uses for key health care stakeholders. Currently, PROs are used in drug development, aligning patient and clinician goals in care, quality-of-care measures, and coverage and reimbursement decisions. While there have been significant strides by key health care stakeholders to further the development and use of PROs, there are a number of challenges limiting more widespread use. In light of these current challenges and the potential for PROs to improve health care quality and value, on October 19, 2017, the Academy of Managed Care Pharmacy convened a forum of key stakeholders representing patients, payers, providers, government, and pharmaceutical companies to discuss and identify solutions to the current challenges and barriers to further use of PROs. These discussions informed the development of participants' ideal future state in which PROs maximize the goals of all health care stakeholders and the actionable steps required to make the future state a reality. While stakeholders shared unique perspectives throughout the forum, they had consensus on 2 overarching issues: the importance of PROs in defining value, improving patient care, and implementing value based payment models and the need for strong organizational and operational systems to achieve optimal adoption and use. Participants identified several key challenges in PRO use and adoption: achieving a representative patient population, inclusion of PRO data in medication labels, the necessity for both standardized and customizable PROs, and operational and organizational barriers to collecting and analyzing PROs. To overcome these challenges, participants recommended that manufacturers should engage key stakeholders early and throughout the drug development process to ensure the most valid and representative PROs and patient populations will be included. To streamline the PRO collection process, participants suggested engaging pharmacists and other providers who may have more frequent interaction with patients. Participants also recommended that PRO collection and analysis should use common technology platforms, streamline components of clinician care to reduce workflow, and be integrated with claims data to provider payers a better understanding of patient health in real time. Finally, additional work should be done to develop patient-reported outcome measures that contain relevant measures for all healthcare stakeholders. While significant challenges remain in PRO development and adoption, participants agreed that greater use can only be achieved through collaboration and patient centered care. Copyright (C) 2018, Academy of Managed Care Pharmacy. All rights reserved.