Ng, Ding Quan

Abstract Nonmyeloablative-related haploidentical allogeneic stem cell transplantation (NMAC-HID allo-HSCT) has emerged as an additional treatment to achieve durable remission in sickle cell disease (SCD), a prevalent blood disorder characterized by painful vaso-occlusive crises and chronic anemia. The standard of care (SOC) for SCD includes hydroxyurea, pain management, and blood transfusion, but patients with SCD still lose several decades of life expectancy. Gene therapy (GT) for SCD is the other treatment for lifelong disease amelioration in SCD, with accessibility limited by cost and manufacturing capacity in the United States and globally. Two recent prospective studies that evaluated NMAC-HID allo-HSCT validated haploidentical allotransplantation as an efficacious and accessible treatment option in the era of GT. Given the ongoing price negotiation across jurisdictions for GT implementation and the absence of cost-effectiveness data comparing NMAC-HID allo-HSCT and GT, we conducted a cost-effectiveness analysis of NMAC-HID allo-HSCT vs GT vs SOC for adults and children living with SCD. The primary outcomes were the incremental cost-effectiveness ratio and the net monetary benefits across these 3 strategies. The secondary outcome was the maximum cost-effective threshold price for GT compared with NMAC-HID allo-HSCT. Treatment with SOC, NMAC-HID allo-HSCT, and GT accrued 14.3, 20.1, and 22.1 quality-adjusted life-years at costs of $1.22 million, $1.15 million, and $2.75 million, respectively. NMAC-HID allo-HSCT was the cost-effective strategy compared with GT in 100% of 10 000 Monte Carlo iterations across the base case and all scenario analyses. The maximum cost-effective thresholds for GT vs SOC were $1.4 million in the United States and $4200 to $22 000 across India, Nigeria, and Tanzania, depending on willingness-to-pay thresholds.

Abstract Maternal iron deficiency (ID) affects nearly 85% of all pregnancies worldwide by the third trimester and is strongly linked with maternal morbidity, poor birth outcomes, and cognitive and behavioral developmental deficits in children. Despite its burden on maternofetal health, no guidelines exist for routine screening of ID in pregnant individuals in the United States. The World Health Organization uses a diagnostic (ie, nonscreening) ferritin threshold of 15 μg/L for ID in the first trimester of pregnancy, with no guidance for the second and third trimesters. Routine screening for ID in pregnancy could identify a large proportion of mothers who remain undiagnosed and untreated under the current clinical status quo. Accordingly, we conducted, to our knowledge, the first cost-effectiveness analysis of ferritin-based ID screening in pregnant women in the United States, comparing thresholds of (1) 30 μg/L vs (2) 15 μg/L vs (3) no screening from a modified US societal perspective accounting for wages lost to infusion time, infusion administration costs, and the cost of annual hematology follow-up. We found that screening at 30 μg/L was the preferred strategy across extensive base-case, threshold, and sensitivity analyses and across all examined willingness-to-pay thresholds, with an incremental cost-effectiveness ratio of $34 000/quality-adjusted life year (QALY; 95% credible interval, $32 000-$36 200/QALY) compared with no screening. No parameter variation changed this outcome, and screening at 30 μg/L was favored in 100% of 10 000 Monte Carlo iterations. Population-level regular second- and third-trimester screening for ID using physiologically informed ferritin ranges should be considered for all pregnant women in the United States.

Abstract Iron-deficiency anemia (IDA) affects nearly one-third of women globally, with heavy menstrual bleeding (HMB) being a significant risk factor among those of reproductive age. Despite the substantial burden of HMB-related IDA, patients often face delays in receiving effective treatment. Oral iron is typically used as first-line therapy, despite frequent gastrointestinal side effects and challenges in treatment adherence. This study evaluated the reproductive life span cost-effectiveness of first-line intravenous (IV) vs oral iron therapy for women with HMB and IDA. We developed a Markov model simulating a cohort of women aged 18 to 51 years, comparing first-line treatment with IV iron dextran, IV ferumoxytol, IV iron sucrose, or oral ferrous sulfate. Costs and quality-adjusted life years (QALYs) were estimated from the societal perspective. IV iron dextran was the cost-effective treatment, yielding 19.26 QALYs at a cost of $157 500, compared with 19.10 QALYs at $152 900 for oral ferrous sulfate. The incremental cost-effectiveness ratio for IV iron dextran was $28 600 per QALY. Treatment with IV ferumoxytol and iron sucrose cost $158 300 and $163 500, respectively, and did not provide additional QALY benefit compared with IV iron dextran, which remained the cost-effective treatment across a range of scenarios and sensitivity analyses. Our findings indicate that first-line treatment with IV iron dextran is the cost-effective strategy for managing IDA in women with HMB at commonly accepted willingness-to-pay thresholds. These results support expanding access to IV iron as a first-line option, and highlight the need to reduce treatment delays and insurance-related barriers.

Abstract Introduction: Monoclonal gammopathy of undetermined significance (MGUS) affects over 2 million individuals aged ≥70 in the US. Earlier detection of smoldering multiple myeloma (SMM) and multiple myeloma (MM) in individuals with suspected MGUS via bone marrow biopsy allows for earlier active monitoring and potential intervention, including with daratumumab for high-risk SMM. Risk prediction for the presence of SMM or MM with the iStopMM and Mayo Clinic models leads to decreased individual-patient and population-level resource utilization burden of bone marrow testing with the tradeoff of some missed non-MGUS diagnoses. We sought to quantify the value of earlier diagnosis, while additionally accounting for the recent results of the AQUILA trial, by assessing the lifetime cost-effectiveness of bone marrow testing strategies for patients with suspected MGUS. Methods: In this independent analysis free of industry influence, we used a decision tree with nested Markov cohort models to evaluate diagnosis and disease progression from MGUS and SMM to MM across 3 diagnostic strategies employing: (1) iStopMM risk prediction model versus (2) Mayo Clinic risk stratification and prediction model versus (3) a test-all strategy. Both risk prediction model performance characteristics were derived from the largest population-level prospective cohort study. Individuals in the MGUS state were monitored annually for disease progression with blood tests. The SMM state included two groups: those correctly diagnosed through biopsy and those misclassified as MGUS due to not undergoing biopsy under the prediction model triage rules (missed SMM diagnosis). As recommended by guidelines, diagnosed patients with non–low-risk SMM were monitored with blood tests every three months; those with low-risk SMM were tested every six months. All diagnosed SMM patients underwent imaging for bone lesions at diagnosis and annually for up to five years. Missed SMM patients were monitored at the same frequency as those with MGUS until disease progression. Early versus delayed myeloma diagnosis complications were informed by real-world multi-institutional quasi-experimental data of consecutively diagnosed patients with MM. MM treatment and outcomes across up to four lines of therapy were modeled exactly as previously published in a validated model. In additional scenario analyses, we assessed the impact of daratumumab monotherapy in the care of people with high-risk SMM across all 3 testing strategies by incorporating the progression free survival and overall survival benefit as reported in the phase 3 AQUILA study. The primary outcome was the incremental net monetary benefit (iNMB), reported across all accepted US willingness-to-pay (WTP) thresholds from a US health system perspective. We concluded with extensive deterministic sensitivity analyses and additionally quantified uncertainty across all model parameters simultaneously with 10,000 Monte Carlo simulations. Results: The iStopMM model was the cost-effective strategy yielding the highest NMB of all strategies at every WTP threshold, with per-patient cost and effectiveness of $188,300 and 10.21 QALYs, respectively. This strategy was dominant—costing less and producing more QALYs—than both the Mayo Clinic and test-all strategies. At the population level, use of the iStopMM model over the Mayo Clinic model and the test-all strategy yields iNMBs of $0.67 [95% CI: 0.2 – 1.14] billion and $3.13 [95%CI: 2.80-3.47] billion, respectively, in favor of the iStopMM strategy. The iStopMM strategy was the cost-effective strategy in 100% of 10,000 second order Monte Carlo iterations. In deterministic sensitivity analyses, the top three parameters the iNMB was most sensitive to were prediction model test characteristics (i.e., sensitivity and specificity) as well as the baseline prevalence of SMM. However, no parameter variation could change the conclusion that iStopMM is the cost-effective strategy. In scenario analyses incorporating benefit of daratumumab monotherapy in the care of individuals with high-risk SMM, the iStopMM model remained the cost-effective strategy. Conclusion: Using the iStopMM risk prediction model for marrow sampling in patients with suspected MGUS leads to cost savings per patient evaluated, both with and without incorporating daratumumab benefit in the care of individuals with high-risk SMM, as compared to both the Mayo Clinic model and testing all with bone marrow biopsy.

Abstract Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect that is highly prevalent among cancer patients undergoing chemotherapy. There is a growing use of cryotherapy (CryTx) and compression therapy (ComTx) to prevent CIPN at cancer centers worldwide. In this study, we examined the awareness and recommendation of these modalities and evaluated factors associated with awareness. In addition, we investigated the type of technology utilized, barriers to implementation, and perceived adverse events of CryTx and ComTx.Methods: Active members of the Multinational Association of Supportive Care of Cancer (MASCC) were invited to complete an electronic survey that was sent via SurveyMonkey between September to October 2021. The survey assessed participants’ awareness, recommendation, usage, barriers to utilization, and perceived adverse events of CryTx and ComTx. Descriptive statistics and multiple logistic regression were utilized to analyze findings.Results: Out of 184 participants, 70.1% were physicians, 73.4% had over 10 years of practice, and 49.5% were practicing in an outpatient setting. While more than half (63.3%) of participants indicated awareness of CryTx for taxane-induced peripheral neuropathy, less than a quarter (22.8%) indicated recommendation in their practice setting. Factors associated with higher awareness of CryTx for patients receiving taxanes include living in Europe (OR=2.69, 95% CI [1.28-5.64], p=0.009), not practicing in an inpatient setting (OR=3.15, 95% CI [1.45-6.85], p=0.004), and self-identifying as non-physician (OR=2.40, 95% CI [1.03-4.37], p=0.041). Commercial cooling (31.5%) and compression (16.8%) gloves and socks were the most used modalities for CryTx and ComTx, respectively. The most identified barriers to CryTx and ComTx utilization include insufficient evidence (53.5%), logistics (34.8%), and patient discomfort (23.4%). Redness/irritation of skin (27.7%) and numbness/tingling (24.5%) accounted for about half of the perceived adverse events associated with use of CryTx and ComTx. Conclusion: Results of our global survey illustrated that there are varying modes in the delivery of CryTx and ComTx among cancer centers around the world. Education of the utilization of CryTx and ComTx, in addition to efficacy and implementation studies, are needed to close the gap between awareness and implementation in clinical practice.