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Introduction: In May 2022, the Centers for Disease Control and Prevention disseminated an alert advising that "a few" persons with Nirmatrelvir/ritonavir (NM/R)-associated rebound of COVID-19 infection had been identified. Three case reports appearing as pre-print postings described the first cases. Analyses in March 2023 by NM/R's manufacturer and the Food and Drug Administration (FDA) reported no association between NM/R and COVID-19 rebound in a large phase 3 randomized clinical trial. Our study evaluated if social media databases or electronically disseminated new articles might provide insights related to the putative new toxicity, NM/R-associated COVID-19 rebound. Methods: Information on NM/R-associated COVID-19 rebound cases was abstracted from preprint postings of non-peer-reviewed manuscripts, social media websites, electronically disseminated print and television media reports, a new FDA adverse event database for drugs that received Emergency Use Approval, and news articles in scientific journals. Results: Thirty-five persons experienced presumed or documented NM/R-associated COVID-19 rebound, based on information described in preprint services (n = 27), Twitter postings and related news articles (n = 7), and news articles without related Twitter reports (n = 1). These reports included information on dates of initial COVID-19 illness and rebound onset, COVID-19 testing, vaccine status, presentation, and outcome. A new FDA safety database identified 12,500 possible cases of this toxicity, but the quality of these data was poor. Preprint postings preceded peer-reviewed publications describing the same cases by four months. Social media websites including Instagram, Reddit, YouTube, the Center for Disease Control and Prevention's (CDC) Health Alert Network, CDC Twitter, and Facebook did not provide clinically meaningful information on individual cases. Conclusion: Preprint services and Twitter facilitated identification of the largest case series of NM/R-associated COVID-19 rebound. The cases were reported in non-peer-reviewed media several weeks prior to the first peer-reviewed electronically disseminated publication of one person with this diagnosis. [ABSTRACT FROM AUTHOR]

The article reports on the investigation by the U.S. Congress on the pricing and market protection by drug makers of anti-multiple myeloma agent lenalidomide. Topics mentioned include the impact of the tactics used by drug makers on patients and Medicare, the use of risk evaluation and mitigation strategy, called RevAssist, to prevent generic competition and the factors that influenced the pricing activity of lenalidomide.

The T‐cell Lymphoma Project is an international registry prospective study that enrolled patients with newly diagnosed peripheral T‐cell and NK‐cell lymphomas (PTCL). The main objective was to define the clinical features and outcomes, establishing a robust benchmark for future clinical trials. Seventy‐four institutions from 14 countries in North America, South America, Europe, and Asia collected data on patients diagnosed and treated at their respective centers between September 2006 and February 2018. Among 1553 PTCL patients, 131 (8.4% of the total cohort) were confirmed to have anaplastic large cell lymphoma ‐ kinase positive (ALCL, ALK+). The median age of the patients was 39 years (18–84). Sixty‐five patients (66%) had advanced‐stage disease, although majority (45 patients, 54%) had a low‐risk International Prognostic Index (IPI) score (0–1). Of 97 patients treated with chemotherapy, 97% received anthracycline‐containing regimens. The overall response rate was 81%, with 69 patients (70%) achieving complete remission. Estimated OS and PFS at 3 years were 77% (95% CI: 54%–99%) and 68% (95% CI: 46%–90%), respectively, and at 5 years were very similar, 77% of OS (95% CI: 62%–92%) and 64% of PFS (95% CI: 34%–94%). Multivariate analysis for PFS showed advanced stage (hazard ratios [HR]: 4.72, 95% CI: 1.43–23.9, p = 0.015), elevated lactate dehidrogenade (LDH) (HR 4.85; 95% CI: 1.73–13.60, p = 0.001), and Eastern Cooperative Oncology Group Performance Status scale (ECOG‐PS) ≥2 (HR: 5.25; 95% CI: 1.68–16.4, p = 0.024). For OS, elevated LDH (HR: 3.77; 95% CI: 1.98–14.17, p = 0.014) and ECOG‐PS ≥2 (HR: 4.59; 95% CI: 1.46–14.39, p = 0.004) were identified. In summary, although the outcome of ALK+ ALCL is superior to that of other PTCLs, it remains sufficiently favorable, given the young median age of the patients. Our results confirm the usefulness of both IPI and Prognostic Index for T‐cell Lymphoma (PIT) in identifying groups of patients with different outcomes. Clinical Trials ID: NCT01142674. [ABSTRACT FROM AUTHOR]

A study was conducted to evaluate the structure, operations, and preliminary findings from the Research on Adverse Drug events And Reports (RADAR) project and related dissemination efforts by pharmaceutical suppliers and the US Food and Drug Administration. The result showed that a new, clinically based, hypothesis-driven approach to postmarketing surveillance may supplement existing regulatory surveillance and improve patients safety.

This report examined the benefits and risks of palbociclib plus endocrine therapy (ET) in men with hormone receptor‒positive (HR+)/human epidermal growth factor receptor 2−negative (HER2−) metastatic breast cancer (MBC). Palbociclib was evaluated using three independent data sources: real‐world data from pharmacy and medical claims, a de‐identified real‐world data source derived from electronic health records (EHRs), and a global safety database. From medical and pharmacy records, 1,139 men with MBC were identified; in the first‐line setting, median duration of treatment was longer with palbociclib plus ET (n = 37, 8.5 months, 95% confidence interval (CI), 4.4‒13.0) than ET alone (n = 214, 4.3 months, 95% CI, 3.0‒5.7) and specifically, was longer with palbociclib plus letrozole (n = 26, 9.4 months, 95% CI, 4.4‒14.0) than letrozole alone (n = 63, 3.0 months, 95% CI, 1.8‒4.8). In the EHR‐derived database, 59 men received treatment for MBC; real‐world response across all lines of therapy in the metastatic setting was reported in 4 of 12 patients (33.3%) in the palbociclib plus ET group vs. 1 of 8 (12.5%) patients in the ET group. Review of the global safety database did not identify any new safety signals in palbociclib‐treated men. Real‐world data indicated that men with MBC benefit from palbociclib plus ET, with a safety profile consistent with previous observations in women with MBC. Collective data on palbociclib in women and men in this report, including clinical trial data, real‐world data, and a well‐established risk/benefit profile, led to US approval of an expansion of the palbociclib indication to include men with MBC. [ABSTRACT FROM AUTHOR]

Biosimilars are biologic drug products that are highly similar to reference products in analytic features, pharmacokinetics and pharmacodynamics, immunogenicity, safety, and efficacy. Biosimilar epoetin received Food and Drug Administration (FDA) approval in 2018. The manufacturer received an FDA nonapproval letter in 2017, despite receiving a favorable review by FDA's Oncologic Drugs Advisory Committee (ODAC) and an FDA nonapproval letter in 2015 for an earlier formulation. We discuss the 2018 FDA approval, the 2017 FDA ODAC Committee review, and the FDA complete response letters in 2015 and 2017; review concepts of litigation, naming, labeling, substitution, interchangeability, and pharmacovigilance; review European and U.S. oncology experiences with biosimilar epoetin; and review the safety of erythropoiesis‐stimulating agents. In 2020, policy statements from AETNA, United Health Care, and Humana indicated that new epoetin oncology starts must be for biosimilar epoetin unless medical need for other epoetins is documented. Empirical studies report that as of 2012, reference epoetin use decreased from 40%–60% of all patients with cancer with chemotherapy‐induced anemia to <5% of such patients because of safety concerns. Between 2018 and 2020, biosimilar epoetin use varied, increasing to 81% among one private insurer's patients covered by Medicare whose cancer care is administered with Oncology Analytics and to 41% with the same private insurer's patients with cancer covered by commercial health insurance and administered by the private insurer, to 0% in several Veterans Administration Hospitals, increasing to 100% in one large county hospital in California, and with yet‐to‐be‐reported data from most oncology settings. We conclude that biosimilar epoetin appears to have overcome some barriers since 2015, although current uptake in the U.S. is variable. Pricing and safety considerations for all erythropoiesis‐stimulating agents are primary determinants of biosimilar epoetin oncology uptake. Implications for Practice: Few oncologists understand substitution and interchangeability of biosimilars with reference drugs. Epoetin biosimilar is new to the market, and physician and patient understanding is limited. The development of epoetin biosimilar is not familiar to oncologists. This review focuses on the development current use of the biosimilar epoetin, which received FDA approval in 2018. [ABSTRACT FROM AUTHOR]

Erythropoisis stimulating agent (ESA) use was addressed in Food and Drug Administration (FDA) Oncology Drug Advisory Committee (ODAC) meetings between 2004 and 2008. FDA safety-focused regulatory actions occurred in 2007 and 2008. In 2007, black box warnings advised of early death and venous thromboembolism (VTE) risks with ESAs in oncology. In 2010, a Risk Evaluation Strategies (REMS) was initiated, with cancer patient consent that mortality and VTE risks were noted with ESAs. We report warnings and REMS impacts on ESA utilization among Veterans Administration (VA) cancer patients with chemotherapy-induced anemia (CIA). Data were from Veterans Affairs database (2003–2012). Epoetin and darbepoetin use were primary outcomes. Segmented linear regression was used to estimate changes in ESA use levels and trends, clinical appropriateness, and adverse events (VTEs) among chemotherapy-treated cancer patients. To estimate changes in level of drug prescription rate after policy actions, model-specific indicator variables as covariates based on specific actions were included. ESA use fell by 95% and 90% from 2005, for epoetin and darbepoetin, from 22% and 11%, respectively, to 1% and 1%, respectively, among cancer patients with CIA, respectively (p<0.01). Following REMS in 2010, mean hematocrit levels at ESA initiation decreased from 30% to 21% (p<0.01). Black box warnings preceded decreased ESA use among VA cancer patients with CIA. REMS was followed by reduced hematocrit levels at ESA initiation. Our findings contrast with privately- insured and Medicaid insured cancer patient data on chemotherapy-induced anemia where ESA use decreased to 3% to 7% by 2010–2012. By 2012, the era of ESA administration to VA to cancer patients had ended but the warnings remain relevant and significant. In 2019, oncology/hematology national guidelines (ASCO/ASH) recommend that cancer patients with chemotherapy-induced anemia should receive ESAs or red blood cell transfusions after risk-benefit evaluation. [ABSTRACT FROM AUTHOR]

Background: The effect of metformin use on survival among patients with pancreatic ductal adenocarcinoma (PDAC) is controversial. Furthermore, there are no data on African American patients. To address these, we analyzed data from the United States Veterans Health Administration (VHA). Methods: A population-based retrospective cohort study evaluating overall survival among 3,811 patients with PDAC with preexisting diabetes mellitus, diagnosed with PDAC within the VHA between 1998 and 2013. We calculated HRs and 95% confidence intervals (CI) using multivariable adjusted time-varying Cox proportional hazards regression to control for immortal time bias and confounders. Results: Metformin use was not associated with overall survival in the complete analyses (HR = 1.05; 95% CI, 0.92-1.14; P = 0.28). However, among patients who were metformin naïve at the time of PDAC diagnosis (N = 1,158), metformin use was associated with improved overall survival in non-Hispanic white patients (HR = 0.78; 95% CI, 0.61-0.99; P = 0.04), but not African American patients (HR = 1.20; 95% CI, 0.75-1.93; P = 0.45). The survival benefit among non-Hispanic whites was limited to patients with metastatic disease (HR = 0.67; 95% CI, 0.44-1.01; P = 0.06). Among African American patients with metastatic disease, HR was 1.30 (95% CI, 0.77-2.53; P = 0.28). There was a suggestion of heterogeneity by race in patients with metastatic disease (Pheterogeneity = 0.05). Conclusions: We observed no associations between metformin use and survival in patients with PDAC, but there appears to be a survival benefit among non-Hispanic white patients who were metformin naïve at the time of PDAC diagnosis. [ABSTRACT FROM AUTHOR]

Background: Multiple myeloma is a common hematologic malignancy consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). Little is known about postdiagnosis clinical predictors of progression of MGUS to multiple myeloma to guide MGUS management. This study aimed to investigate whether the rate of rise in serum monoclonal protein concentration during the year after MGUS diagnosis--M-protein velocity--predicts progression of MGUS to multiple myeloma. Methods: Data from the U.S. Veterans Health Administration system were used. A retrospective cohort of patients with MGUS who progressed to multiple myeloma were matched on age at MGUS diagnosis and race in a 1:4 ratio to the patients with MGUS using incidence density sampling. Kaplan-Meier curves were plotted. Univariable and multivariable conditional logistic regression analyses were fitted from the matched risk sets. Results: A total of 128 cases and 490 matched controls were included. The case group contained a higher percentage of patients with M-protein velocity >0.1 g/dL/year than the control group (44.5% vs. 28.2%, P <0.0001). M-protein velocity of >0.1 g/dL during the year following MGUS diagnosis was positively associated with progression of MGUS to multiple myeloma (multivariable-adjusted odds ratio = 2.15; 95% confidence interval, 1.37-3.35). Conclusions: Patients with a positive M-protein velocity during the year after MGUS diagnosis may be considered for more frequent monitoring for early detection and timely treatment of multiple myeloma. Future prevention studies could target these patients for intervention evaluation. Impact: Our results suggest a new clinical predictor of progression to multiple myeloma following MGUS diagnosis, which has potential to identify high-risk patients for management and prevention. [ABSTRACT FROM AUTHOR]