Linvoseltamab for Treatment of Relapsed/Refractory Multiple Myeloma.

PURPOSE: We present a phase I/II first-in-human trial evaluating the safety and efficacy of 50 mg and 200 mg doses of linvoseltamab, a B-cell maturation antigen × CD3 bispecific antibody in relapsed/refractory multiple myeloma (RRMM). METHODS: Phase II eligible patients had RRMM that either progressed on/after ≥three lines of therapy including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 antibody or was triple-class (PI/IMiD/anti-CD38) refractory. Phase II treatment was once a week through week 14 and then once every 2 weeks. Phase II 200 mg patients who achieved a ≥very good partial response by week 24 received linvoseltamab once every 4 weeks. The primary end point in phase II was overall response rate (ORR). RESULTS: Among the 117 patients treated with 200 mg, the median age was 70 years, 39% had high-risk cytogenetics, and 28% had penta-refractory disease. At a median follow-up of 14.3 months, the ORR was 71%, with 50% achieving ≥complete response (CR). In 104 patients treated with 50 mg at a median follow-up of 7.4 months, the ORR was 48%, with 21% achieving ≥CR. The median duration of response (DOR) for 200 mg patients (n = 83) was 29.4 months (95% CI, 19.2 to not evaluable). Among 200 mg patients, the most common adverse events included cytokine release syndrome (35.0% Gr1, 10.3% Gr2, 0.9% Gr3), neutropenia (0.9% Gr2, 18.8% Gr3, 23.1% Gr4), and anemia (3.4% Gr1, 4.3% Gr2, 30.8% Gr3). Immune effector cell-associated neurotoxicity syndrome occurred in 7.7% of patients (2.6% each Gr1, Gr2, Gr3). Infections were reported in 74.4% of patients (33.3% Gr3, 2.6% Gr4); infection frequency and severity declined over time. CONCLUSION: Linvoseltamab 200 mg induced deep and durable responses, with a median DOR of 29.4 months, in patients with RRMM with an acceptable safety profile.

Minimal Residual Disease-Adapted Therapy in Multiple Myeloma: Current Evidence and Opinions.

PURPOSE OF REVIEW: Multiple myeloma (MM) is a biologically heterogeneous malignancy with relatively uniform treatment paradigms. This review aims to assess the growing role of Minimal Residual Disease (MRD) assessment in facilitating response-adapted therapeutic decision making to individualize therapy in MM. RECENT FINDINGS: MRD has been repeatedly demonstrated to provide strong prognostic information, superseding traditional IMWG response criteria. The use of MRD to modulate therapy remains controversial. Here, we review the existing landscape of MRD-adapted trial designs in both induction/consolidation and maintenance settings, including recent data from influential studies and retrospective analyses. We navigate existing data, leverage the increased resolution of longitudinal MRD assessments, and comment on trials in progress to explain our current utilization of MRD in the clinic. MRD transcends traditional response assessments by providing a window into disease-treatment interaction over time. As a strong patient-level surrogate, MRD has limited current use in individualizing treatment, but is poised to comprehensively shape treatment strategies at many key points in a patient's MM course.

National trends in prescription drug expenditures and projections for 2024.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2024 in the United States, with a focus on the nonfederal hospital and clinic sectors. METHODS: Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2024 were reviewed-including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, endocrine drugs, generics, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2024 were based on a combination of quantitative analyses and expert opinion. RESULTS: In 2023, overall pharmaceutical expenditures in the US grew 13.6% compared to 2022, for a total of $722.5 billion. Utilization (a 6.5% increase), new drugs (a 4.2% increase) and price (a 2.9% increase) drove this increase. Semaglutide was the top drug in 2023, followed by adalimumab and apixaban. Drug expenditures were $37.1 billion (a 1.1% decrease) and $135.7 billion (a 15.0% increase) in nonfederal hospitals and clinics, respectively. In clinics, increased utilization drove growth, with a small impact from price and new products. In nonfederal hospitals, a drop in utilization led the decrease in expenditures, with price and new drugs modestly contributing to growth in spending. Several new drugs that will influence spending are expected to be approved in 2024. Specialty, endocrine, and cancer drugs will continue to drive expenditures. CONCLUSION: For 2024, we expect overall prescription drug spending to rise by 10.0% to 12.0%, whereas in clinics and hospitals we anticipate an 11.0% to 13.0% increase and a 0% to 2.0% increase, respectively, compared to 2023. These national estimates of future pharmaceutical expenditure growth may not be representative of any health system because of the myriad of local factors that influence actual spending.

Emerging Strategies for the Prevention of Immune Toxicities Associated with T cell-Engaging Cancer Therapies.

SUMMARY: Immune-related toxicities including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are common side effects of bispecific antibody and chimeric antigen receptor (CAR) T-cell therapies of hematologic malignancies. As anti-inflammatory therapy (the standard of care) is variably effective in mitigating these toxicities after onset, here we discuss emerging evidence for shifting the strategy from mitigation to prevention.

Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: Transthyretin amyloid cardiomyopathy is characterized by the deposition of misfolded monomeric transthyretin (TTR) in the heart. Acoramidis is a high-affinity TTR stabilizer that acts to inhibit dissociation of tetrameric TTR and leads to more than 90% stabilization across the dosing interval as measured ex vivo. METHODS: In this phase 3, double-blind trial, we randomly assigned patients with transthyretin amyloid cardiomyopathy in a 2:1 ratio to receive acoramidis hydrochloride at a dose of 800 mg twice daily or matching placebo for 30 months. Efficacy was assessed in the patients who had an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m2 of body-surface area. The four-step primary hierarchical analysis included death from any cause, cardiovascular-related hospitalization, the change from baseline in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, and the change from baseline in the 6-minute walk distance. We used the Finkelstein-Schoenfeld method to compare all potential pairs of patients within strata to generate a P value. Key secondary outcomes were death from any cause, the 6-minute walk distance, the score on the Kansas City Cardiomyopathy Questionnaire-Overall Summary, and the serum TTR level. RESULTS: A total of 632 patients underwent randomization. The primary analysis favored acoramidis over placebo (P<0.001); the corresponding win ratio was 1.8 (95% confidence interval [CI], 1.4 to 2.2), with 63.7% of pairwise comparisons favoring acoramidis and 35.9% favoring placebo. Together, death from any cause and cardiovascular-related hospitalization contributed more than half the wins and losses to the win ratio (58% of all pairwise comparisons); NT-proBNP pairwise comparisons yielded the highest ratio of wins to losses (23.3% vs. 7.0%). The overall incidence of adverse events was similar in the acoramidis group and the placebo group (98.1% and 97.6%, respectively); serious adverse events were reported in 54.6% and 64.9% of the patients. CONCLUSIONS: In patients with transthyretin amyloid cardiomyopathy, the receipt of acoramidis resulted in a significantly better four-step primary hierarchical outcome containing components of mortality, morbidity, and function than placebo. Adverse events were similar in the two groups. (Funded by BridgeBio Pharma; ATTRibute-CM ClinicalTrials.gov number, NCT03860935.).

Genomic and immune signatures predict clinical outcome in newly diagnosed multiple myeloma treated with immunotherapy regimens.

Despite improving outcomes, 40% of patients with newly diagnosed multiple myeloma treated with regimens containing daratumumab, a CD38-targeted monoclonal antibody, progress prematurely. By integrating tumor whole-genome and microenvironment single-cell RNA sequencing from upfront phase 2 trials using carfilzomib, lenalidomide and dexamethasone with daratumumab ( NCT03290950 ), we show how distinct genomic drivers including high APOBEC mutational activity, IKZF3 and RPL5 deletions and 8q gain affect clinical outcomes. Furthermore, evaluation of paired bone marrow profiles, taken before and after eight cycles of carfilzomib, lenalidomide and dexamethasone with daratumumab, shows that numbers of natural killer cells before treatment, high T cell receptor diversity before treatment, the disappearance of sustained immune activation (that is, B cells and T cells) and monocyte expansion over time are all predictive of sustained minimal residual disease negativity. Overall, this study provides strong evidence of a complex interplay between tumor cells and the immune microenvironment that is predictive of clinical outcome and depth of treatment response in patients with newly diagnosed multiple myeloma treated with highly effective combinations containing anti-CD38 antibodies.

Safety and Efficacy of Traditional Heart Failure Therapies in Patients With Cardiac Amyloidosis and Heart Failure.

Randomized controlled trials have demonstrated mortality benefits for several medication classes in patients with heart failure (HF), especially with reduced ejection fraction (EF). However, the benefit of these traditional HF therapies in patients with HF from cardiac amyloidosis is unclear. our study aimed to evaluate the safety and efficacy of traditional HF therapies in patients with cardiac amyloidosis and HF with reduced EF or HF with mid-range EF (HFmrEF). We conducted a single-center retrospective study. Patients were included if they were diagnosed with cardiac amyloidosis and HF with reduced EF or HF with mid-range EF between January 2012 and 2022. The primary outcomes of interest were medication use patterns (for ß blockers [BB], angiotensin-converting enzyme inhibitors [ACEI], angiotensin receptor blockers [ARBs], angiotensin receptor neprilysin inhibitors [ARNI], and mineralocorticoid receptor antagonists [MRAs]); potential medication side effects (symptomatic bradycardia, fatigue, hypotension, lightheadedness, and syncope); hospitalization; and death. The associations of BB, ACEI/ARB/ARNI, and MRA use with clinical outcomes were evaluated using Kaplan-Meier and Cox proportional hazards regression. A total of 82 patients met study criteria. At time of cardiac amyloidosis diagnosis, 63.4% were on a BB, 51.2% were on an ACEI/ARB/ARNI, and 43.9% were on an MRA. At last follow-up, 51.2% were on a BB, 35.4% were on an ACEI/ARB/ARNI, and 43.9% were on an MRA. There were no statistically significant differences in rates of potential medication side effects in patients on the medication class compared with those who were not. There was no association with hospitalization or mortality for baseline or follow-up BB, ACEI/ARB/ARNI, or MRA use. In conclusion, BBs, ACEI/ARB/ARNIs, and MRAs may be safely used in this population. However, their use does not appear to improve mortality or hospitalization.

National trends in prescription drug expenditures and projections for 2023.

PURPOSE: To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2023 in the United States, with a focus on the nonfederal hospital and clinic sectors. METHODS: Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2023 were reviewed, including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, diabetes medications, generics, COVID-19 pandemic influence, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2023 were based on a combination of quantitative analyses and expert opinion. RESULTS: In 2022, overall pharmaceutical expenditures in the US grew 9.4% compared to 2021, for a total of $633.5 billion. Utilization (a 5.9% increase), price (a 1.7% increase) and new drugs (a 1.8% increase) drove this increase. Adalimumab was the top-selling drug in 2022, followed by semaglutide and apixaban. Drug expenditures were $37.2 billion (a 5.9% decrease) and $116.9 billion (a 10.4% increase) in nonfederal hospitals and clinics, respectively. In clinics, new products and increased utilization growth drove growth, with a small impact from price changes. In nonfederal hospitals, a drop in utilization led to a decrease in expenditures, with price changes and new drugs contributing to growth in spending. Several new drugs that will influence spending have been or are expected to be approved in 2023. Specialty and cancer drugs will continue to drive expenditures along with the evolution of the COVID-19 pandemic. CONCLUSION: For 2023, we expect overall prescription drug spending to rise by 6.0% to 8.0%, whereas in clinics and hospitals we anticipate increases of 8.0% to 10.0% and 1.0% to 3.0%, respectively, compared to 2022. These national estimates of future pharmaceutical expenditure growth may not be representative of any particular health system because of the myriad of local factors that influence actual spending.

Building new standards to prevent harm from medication errors in children with cancer.

Children with cancer receive many medications outside the hospital administered by their caregivers. The study by Walsh et al. shows the number and types of medication errors in these patients. The study includes data from three different centers. Importantly, the study shows the types of errors that cause harm. The authors describe how the harmful errors can be prevented. We suggest ways these results can be used to identify which patients and families will benefit from additional attention. Providing more help at clinic and in the home may help prevent harmful medication errors in children with cancer.

Long-term survival in people with transthyretin amyloid cardiomyopathy who took tafamidis: A Plain Language Summary.

WHAT IS THIS PLAIN LANGUAGE SUMMARY ABOUT?: This summary presents the results from an ongoing, long-term extension study that followed an earlier study called ATTR-ACT. People who took part in this extension study and ATTR-ACT have a type of heart disease known as transthyretin amyloid cardiomyopathy (ATTR-CM for short), which causes heart failure and death. In ATTR-ACT, people took either a medicine called tafamidis or a placebo (a pill that looks like the study drug but does not contain any active ingredients) for up to 2½ years. So far, in the long-term extension study, people have continued taking tafamidis, or switched from taking a placebo to tafamidis, for another 2½ years. Researchers looked at how many people died in ATTR-ACT and the extension study. The long-term extension study is expected to end in 2027, so these are interim (not final) results. WHAT DID RESEARCHERS FIND OUT?: In the extension study of ATTR-ACT, the risk of dying was lower in people who took tafamidis continuously throughout ATTR-ACT and the extension study than in people who took placebo in ATTR-ACT and switched to tafamidis in the extension study. WHAT DO THE RESULTS MEAN?: Taking tafamidis increases how long people with ATTR-CM live. People with ATTR-CM who take tafamidis early and continuously are more likely to live longer than those who do not. These results highlight the importance of early detection and treatment in people with ATTR-CM. Clinical Trial Registration: NCT01994889 (ClinicalTrials.gov) Clinical Trial Registration: NCT02791230 (ClinicalTrials.gov).

Safety and efficacy of letetresgene autoleucel alone or with pembrolizumab for relapsed/refractory multiple myeloma.

This pilot study assessed the safety and efficacy of letetresgene autoleucel (lete-cel; GSK3377794), a genetically modified autologous T-cell therapy targeting New York esophageal squamous cell carcinoma-1 (NY-ESO-1)/L antigen family member 1 isoform A (LAGE-1a)-positive myeloma cells, alone or in combination with pembrolizumab in patients with relapsed/refractory multiple myeloma. Eligible patients expressed NY-ESO-1 and/or LAGE-1a and either HLA-A∗02:01, ∗02:05, or ∗02:06. Patients received lete-cel single infusion alone (arm 1) or with pembrolizumab (arm 2). 127 patients were screened, and 6 patients (3 per arm) were enrolled; patients in arm 1 and 2 received lete-cel alone, or with pembrolizumab, respectively. All patients exhibited grade 3/4 cytopenias, which resolved or improved to grade 1. One patient (arm 1) had grade 3/4 lete-cel-related adverse events (AEs); 2 patients (arm 2) had grade 3/4 AEs related to lete-cel and lymphodepletion. Three patients with grade 1/2 cytokine release syndrome (CRS) exhibited elevated post-lete-cel interleukin-6 levels versus those without CRS. Pooled overall response rate was 50% including 1 patient each with confirmed clinical response, very good clinical response, and partial response, and progression-free survival ranged from 1.3 to 5.2 months. Responders (arm 1: n = 1; arm 2: n = 2) had a time-to-response of 3 weeks, duration of response of 2.1 months. Two responders, but no nonresponders, exhibited elevated cytokine levels after lete-cel infusion. Lete-cel had a manageable safety profile and demonstrated clear but transient antitumor activity in patients with relapsed/refractory multiple myeloma. This trial was registered at www.clinicaltrials.gov as #NCT03168438.

Real-world treatment patterns, costs, and outcomes in patients with AL amyloidosis: analysis of the Optum EHR and commercial claims databases.

BACKGROUND: This study characterised real-world treatment patterns, clinical outcomes, and cost-of-illness in patients with light-chain (AL) amyloidosis. METHODS: Data were extracted from the US-based Optum® EHR and Clinformatics® Data Mart (claims) databases (2008-2019) for patients newly diagnosed with AL amyloidosis and who initiated anti-plasma cell therapies. Healthcare resource utilisation (HCRU) and related costs were compared across lines of therapy (LOT). Incidences of cardiac and renal failure were evaluated using the Kaplan-Meier method. RESULTS: About 1347 patients (EHR, n = 776; claims, n = 571) were included. Median age was 68 years; 56.8% were male. At initial diagnosis, 33.1% and 15.1% of patients had cardiac and renal failure, respectively. Most patients received bortezomib-containing treatment in LOT1 (69%); bortezomib-cyclophosphamide-dexamethasone was most common (26%). HCRU was similar across LOTs. Mean per-patient-per-month and per-patient-per-LOT costs were $19,343 and $105,944 for LOT1, $19,183 and $95,793 for LOT2, and $16,611 and $128,446 for LOT3, respectively. Costs were primarily driven by anti-plasma cell therapies, outpatient visits, and hospitalisations. The 5-year cardiac and renal failure rates following initial diagnosis were 64.5% and 39.0%, respectively. CONCLUSION: AL amyloidosis is associated with substantial costs and suboptimal outcomes, highlighting the need for new therapeutic approaches to prevent organ deterioration, and reduce disease burden.

Employee investigation and contact tracing program in a pediatric cancer hospital to mitigate the spread of COVID-19 among the workforce, patients, and caregivers.

Background: Case investigations and contact tracing are essential disease control measures used by health departments. Early in the pandemic, they were seen as a key strategy to stop COVID-19 spread. The CDC urged rapid action to scale up and train a large workforce and collaborate across public and private agencies to halt COVID-19 transmission. Methods: We developed a program for case investigation and contact tracing that followed CDC and local health guidelines, compliant with the Occupational Safety and Health Administration (OSHA) regulations and tailored to the needs and resources of our institution. Program staff were trained and assessed for competency before joining the program. Results: From March 2020 to May 2021, we performed 838 COVID-19 case investigations, which led to 136 contacts. Most employees reported a known SARS-CoV-2 exposure from the community (n = 435) or household (n = 343). Only seven (5.1%) employees were determined as more likely than not to have SARS-CoV-2 infection related to workplace exposure, and when so, lapses in following the masking recommendations were identified. Between June 2021-February 2022, our program adjusted to the demand of the different waves, particularly omicron, by significantly reducing the amount of data collected. No transmission from employees to patients or caregivers was observed during this period. Conclusion: Prompt implementation of case investigation and contact tracing is possible, and it effectively reduces workplace exposures. This approach can be adapted to suit the specific needs and requirements of various healthcare settings, particularly those serving the most vulnerable patient populations.

Combination venetoclax and selinexor effective in relapsed refractory multiple myeloma with translocation t(11;14).

Patients with multiple myeloma-bearing translocation t(11;14) have recently been shown to benefit from the apoptosis-inducing drug venetoclax; however, the drug lacks FDA approval in multiple myeloma thus far due to a potential safety signal in the overall patient population. Selinexor is an inhibitor of nuclear export that is FDA-approved for patients with multiple myeloma refractory to multiple lines of therapy. Here, we report that in four patients with multiple myeloma with t(11;14), the concomitant administration of venetoclax and selinexor was safe and associated with disease response. Moreover, the combination was synergistic in t(11;14) multiple myeloma cell lines and caused decreased levels of Cyclin D1 (which is overexpressed due to the CCND1-IGH fusion) when given in combination as compared to single agents. These data suggest that the combination of venetoclax and selinexor is effective and t(11;14) may serve as a therapeutic marker for response and target for future clinical trials.

Global Myeloma Trial Participation and Drug Access in the Era of Novel Therapies.

PURPOSE: The globalization of clinical trials has accelerated recent advances in multiple myeloma (MM). However, it is unclear whether trial enrollment locations are reflective of the global burden of MM and whether access to novel therapies is timely and equitable for countries that participate in those trials. METHODS: To assess this, we characterized where MM trials that led to US Food and Drug Administration (FDA) approvals were conducted and determined how often and quickly these drug regimens received approval in their participating trial countries on the basis of country income level and geographic region. RESULTS: A systematic review was conducted to identify all MM clinical trials that met their primary endpoint, enrolled patients outside the United States, and resulted in FDA approval from 2005 to 2019. A total of 18 pivotal MM clinical trials were identified. High-income countries enrolled patients in 100% (18/18) of the trials identified, whereas upper-middle and lower-middle-income countries were represented in 61% (11/18) and 28% (5/18) of trials, respectively. No patients from low-income countries were enrolled. One trial enrolled patients in sub-Saharan Africa, and no trials enrolled patients in South Asia/Caribbean. For drugs/regimens that were approved in their participating countries, the median time from FDA approval to approval was 10.9 months. There were no drugs approved in lower-middle-income trial countries. MM trials leading to FDA approval are generally run in high-income, European, and Central Asian countries. CONCLUSION: There are substantial disparities in where novel therapies are evaluated and where they are ultimately approved for use on the basis of income level and geography.

covidscreen: a web app and R Package for assessing asymptomatic COVID-19 testing strategies.

BACKGROUND: COVID-19 has caused over 305 million infections and nearly 5.5 million deaths globally. With complete eradication unlikely, organizations will need to evaluate their risk and the benefits of mitigation strategies, including the effects of regular asymptomatic testing. We developed a web application and R package that provides estimates and visualizations to aid the assessment of organizational infection risk and testing benefits to facilitate decision-making, which combines internal and community information with malleable assumptions. RESULTS: Our web application, covidscreen, presents estimated values of risk metrics in an intuitive graphical format. It shows the current expected number of active, primarily community-acquired infections among employees in an organization. It calculates and explains the absolute and relative risk reduction of an intervention, relative to the baseline scenario, and shows the value of testing vaccinated and unvaccinated employees. In addition, the web interface allows users to profile risk over a chosen range of input values. The performance and output are illustrated using simulations and a real-world example from the employee testing program of a pediatric oncology specialty hospital. CONCLUSIONS: As the COVID-19 pandemic continues to evolve, covidscreen can assist organizations in making informed decisions about whether to incorporate covid test based screening as part of their on-campus risk-mitigation strategy. The web application, R package, and source code are freely available online (see "Availability of data and materials").

Quality improvement knowledge in pediatric hematology/oncology physicians: A need for improved education.

Pediatric hematology/oncology fellows face unique quality improvement challenges given the danger of chemotherapy and caring for immunocompromised patients. Curricula to teach pediatric hematology/oncology fellows about quality improvement are lacking. We conducted a needs assessment of pediatric hematology/oncology physicians as a first step for creating a quality improvement curriculum for pediatric hematology/oncology fellows. Curricular topics were identified: root cause analysis, run charts, process mapping, chemotherapy/medication safety, implementation/adherence to guidelines. Identified barriers to curriculum implementation included a possible lack of quality improvement expertise, lack of awareness of quality improvement resources, and limited time.

National trends in prescription drug expenditures and projections for 2022.

PURPOSE: To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2022 in the United States, with a focus on the nonfederal hospital and clinic sectors. METHODS: Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2022 were reviewed-including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, generics, COVID-19 pandemic influence, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2022 were based on a combination of quantitative analyses and expert opinion. RESULTS: In 2021, overall pharmaceutical expenditures in the US grew 7.7% compared to 2020, for a total of $576.9 billion. Utilization (a 4.8% increase), price (a 1.9% increase) and new drugs (a 1.1% increase) drove this increase. Adalimumab was the top drug in terms of overall expenditures in 2021, followed by apixaban and dulaglutide. Drug expenditures were $39.6 billion (a 8.4% increase) and $105.0 billion (a 7.7% increase) in nonfederal hospitals and in clinics, respectively. In clinics and hospitals, new products and increased utilization growth drove growth, with decreasing prices for both sectors acting as an expense restraint. Several new drugs that are likely to influence spending are expected to be approved in 2022. Specialty and cancer drugs will continue to drive expenditures along with the evolution of the COVID-19 pandemic. CONCLUSION: For 2022, we expect overall prescription drug spending to rise by 4.0% to 6.0%, whereas in clinics and hospitals we anticipate increases of 7.0% to 9.0% and 3.0% to 5.0%, respectively, compared to 2021. These national estimates of future pharmaceutical expenditure growth may not be representative of any particular health system because of the myriad of local factors that influence actual spending.