Comparative effectiveness of lenalidomide/dexamethasone-based triplet regimens for treatment of relapsed and/or refractory multiple myeloma in the United States: An analysis of real-world electronic health records data.

BACKGROUND: This retrospective longitudinal study compared the effectiveness of dexamethasone+lenalidomide (Rd)-based triplet regimens containing proteasome inhibitors (PIs) ixazomib (IRd), carfilzomib (KRd), and bortezomib (VRd) or monoclonal antibodies (MABs) elotuzumab (ERd) and daratumumab (DRd) in patients with relapsed/refractory multiple myeloma (RRMM)-including those with high cytogenetic risk-primarily treated at community oncology clinics in the United States. METHODS: Electronic health records of adult RRMM patients in a deidentified real-world database (01/01/2014-09/30/2020) who initiated IRd, KRd, VRd, ERd, or DRd in the second or later line of therapy (LOT) were analyzed. The index date was the date of initiation of each LOT and baseline was the 6-month pre-index period. Duration of therapy (DOT), time to next therapy (TTNT), progression-free survival (PFS), and overall survival (OS) were compared across regimens with multivariable Cox proportional hazards models. RESULTS: Of the 1,185 patients contributing 1,332 LOTs, 985 had standard cytogenetic risk (median age, 71 years) and 180 had high risk (median age, 69 years). Compared with other regimens, DRd was associated with longer DOT overall (adjusted hazard ratio [95 % confidence interval]: 1.84 [1.42, 2.38] vs. KRd, 1.65 [1.20, 2.28] vs. ERd, 1.58 [1.23, 2.04] vs. IRd, and 1.54 [1.18, 2.00] vs. VRd), and longer TTNT and PFS. KRd was associated with shorter OS compared with DRd (1.45 [1.01, 2.08]) and VRd (1.32 [1.01, 1.73]). High-risk patients had similar outcomes with all triplet regimens. CONCLUSION: Although DRd improved clinical outcomes overall, Rd-based triplet regimens containing a PI or MAB are similarly effective in high-risk RRMM.

Likelihood of Antimicrobial Resistance in Urinary E coli Isolates among US Female Patients with Recurrent vs Non-Recurrent Uncomplicated Urinary Tract Infection.

OBJECTIVE: To assess the relative likelihood of antimicrobial resistance (AMR) and multi-drug resistance (MDR) among E coli isolates from outpatients with recurrent versus non-recurrent uncomplicated urinary tract infection (uUTI). METHODS: In this retrospective observational US cohort study, female outpatients (≥12 years) with uUTI, positive E coli culture, and treated with ≥1 oral antibiotic within ±5 days of diagnosis were grouped into recurrent and non-recurrent uUTI cohorts per their UTI history (past 12 months). AMR to specific drug classes was evaluated at index. Univariable and multivariable logistic regression models estimated the likelihood of not-susceptible E coli isolates (AMR/MDR) among patients with recurrent uUTI versus non-recurrent uUTI. RESULTS: Recurrent (N = 12,234) and non-recurrent (N = 68,033) uUTI cohorts had similar distributions (race, ethnicity, region). Patients with recurrent uUTI had a higher prevalence of E coli resistance to trimethoprim-sulfamethoxazole (21.8% vs 18.7%) and fluoroquinolones (14.2% vs 8.6%), and more isolates were extended-spectrum ß-lactamase-producing (5.9% vs 4.1%) compared to non-recurrent uUTI patients. Patients with recurrent uUTI had a higher likelihood (odds ratio [95% confidence interval]) of any AMR (1.28 [1.22-1.34]), single drug-class resistance (1.18 [1.12-1.24]), and resistance to 2 (1.53 [1.41-1.67]) or ≥3 drug classes (1.70 [1.48-1.96]) (all P <.001). CONCLUSION: This study delineated the likelihood of AMR and MDR among E coli isolates from patients with recurrent versus non-recurrent uUTI. While some treatment guidelines support empiric therapy in recurrent uUTI, the increased likelihood of resistance among these patients suggests that culture and susceptibility testing should be undertaken to inform recurrent uUTI treatment.

Cost of genetic testing, delayed care, and suboptimal treatment associated with polymerase chain reaction versus next-generation sequencing biomarker testing for genomic alterations in metastatic non-small cell lung cancer.

AIMS: To assess US payers' per-patient cost of testing associated with next-generation sequencing (NGS) versus polymerase chain reaction (PCR) biomarker testing strategies among patients with metastatic non-small cell lung cancer (mNSCLC), including costs of testing, delayed care, and suboptimal treatment initiation. METHODS: A decision tree model considered biomarker testing for genomic alterations using either NGS, sequential PCR testing, or hotspot panel PCR testing. Literature-based model inputs included time-to-test results, costs for testing/medical care, costs of delaying care, costs of immunotherapy [IO]/chemotherapy [CTX] initiation prior to receiving test results, and costs of suboptimal treatment initiation after test results (i.e. costs of first-line IO/CTX in patients with actionable mutations that were undetected by PCR that would have been identified with NGS). The proportion of patients testing positive for a targetable alteration, time to appropriate therapy initiation, and per-patient costs were estimated for NGS and PCR strategies combined. RESULTS: In a modeled cohort of 1,000,000 members (25% Medicare, 75% commercial), an estimated 1,119 had mNSCLC and received testing. The proportion of patients testing positive for a targetable alteration was 45.9% for NGS and 40.0% for PCR testing. Mean per-patient costs were lowest for NGS ($8,866) compared to PCR ($18,246), with lower delayed care costs of $1,301 for NGS compared to $3,228 for PCR, and lower costs of IO/CTX initiation prior to receiving test results (NGS: $2,298; PCR:$5,991). Cost savings, reaching $10,496,220 at the 1,000,000-member plan level, were driven by more rapid treatment with appropriate therapy for patients tested with NGS (2.1 weeks) compared to PCR strategies (5.2 weeks). LIMITATIONS: Model inputs/assumptions were based on published literature or expert opinion. CONCLUSIONS: NGS testing was associated with greater cost savings versus PCR, driven by more rapid results, shorter time to appropriate therapy initiation, and minimized use of inappropriate therapies while awaiting and after test results.

Real-world time to discontinuation of first-line venetoclax + obinutuzumab in chronic lymphocytic leukemia/small lymphocytic lymphoma.

OBJECTIVE: To evaluate the time to discontinuation (TTD) and baseline characteristics among patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) treated with first-line (1L) venetoclax + obinutuzumab (VO) in the United States. METHODS: A nationwide electronic health record-derived database was used to select adults with CLL/SLL initiating a 1L venetoclax-based regimen between April 11, 2016-July 31, 2020. Study measures included TTD (defined as >120-day treatment gap or switching therapy) and baseline characteristics by discontinuation status. RESULTS: A total of 113 patients receiving 1L VO on/before July 31, 2020 were eligible for analysis (mean age: 65.9 years; 31.9% women). During the first 60 days post-treatment initiation, 3.5% had tumor lysis syndrome (TLS). The proportion of patients using corticosteroids, anti-hyperuricemics, and anti-emetics was higher during the first 60 days post-treatment initiation (100.0%, 78.8%, and 52.2%, respectively) than the period from day 61 onward (67.0%, 45.5%, and 33.9%, respectively). Mean (median) duration of active treatment was 11.6 (12.1) months; 16.8% discontinued treatment before completing 12 cycles, 68.1% completed ≥12 cycles (among which 29.9% completed ≥15 cycles), and 15.0% who did not discontinue treatment were censored before completing 12 cycles. Kaplan-Meier analysis showed that median TTD was 13.8 months. Relative to those completing ≥12 cycles, patients discontinuing treatment before completing the prescribed 12 cycles were older (70.4 vs. 65.1 years) and had poorer renal function (36.8% vs. 13.0% with creatinine clearance <60 mL/min). CONCLUSION: A small proportion of CLL/SLL patients who were older and had poorer baseline renal function discontinued 1L VO prior to completing 12 treatment cycles. Additionally, treatment utilization, including medications related to TLS mitigation and management, was more intense during the initiation phase of VO. Further research with longer follow-up to assess long-term outcomes of VO treatment after early discontinuation is warranted.

Long-Term Psoriasis Control with Guselkumab, Adalimumab, Secukinumab, or Ixekizumab in the USA.

BACKGROUND: Biologics have revolutionized the management of psoriasis, but response to treatment varies. Loss of treatment efficacy may occur over time, requiring treatment switching or escalation. Claims data on persistence may be informative of real-world treatment outcome. This analysis described persistence and rates of remission of patients with psoriasis initiated on current biologics. METHODS: Adults with psoriasis initiated (index date) on guselkumab, adalimumab, secukinumab, or ixekizumab between 07/13/2017 and 07/31/2020 were identified in the IBM MarketScan Databases. Discontinuation (or end of persistence) was defined as gaps in index biologic supply of more than twice the labelled dosing interval or mode days of supply (> 120 days for guselkumab and > 60 days for adalimumab, secukinumab, and ixekizumab). The proportion of patients reinitiating index therapy post-discontinuation and the proportion achieving remission (proxy definition: no claims for psoriasis-related treatment post-discontinuation among patients with ≥ 6 months of follow-up post-discontinuation) were assessed. RESULTS: There were 3408 patients in the guselkumab (mean age: 47.9 years old; female: 47.1%), 8017 in the adalimumab (47.4 years old; 54.1%), 6123 in the secukinumab (49.4 years old; 54.2%), and 3728 in the ixekizumab cohorts (49.1 years old; 50.3%). The median time to discontinuation was 26.2 months in the guselkumab cohort and 9.9, 12.4, and 12.5 months in adalimumab, secukinumab, and ixekizumab cohorts, respectively. Among those who discontinued index therapy, 22.9% in the guselkumab cohort and 21.1%, 31.9%, and 32.0% in the adalimumab, secukinumab, and ixekizumab cohorts reinitiated it. Remission rates were 17.2% in the guselkumab cohort and 12.4%, 10.5%, and 9.0% in adalimumab, secukinumab, and ixekizumab cohorts, respectively. CONCLUSIONS: Patients on guselkumab showed trends toward better persistence and higher remission rates relative to other biologics. Finding patients who may be in remission suggests potential disease modification with current agents.

Cost Savings of Expedited Care with Upfront Next-Generation Sequencing Testing versus Single-Gene Testing among Patients with Metastatic Non-Small Cell Lung Cancer Based on Current Canadian Practices.

This study assessed the total costs of testing, including the estimated costs of delaying care, associated with next-generation sequencing (NGS) versus single-gene testing strategies among patients with newly diagnosed metastatic non-small cell lung cancer (mNSCLC) from a Canadian public payer perspective. A decision tree model considered testing for genomic alterations using tissue biopsy NGS or single-gene strategies following Canadian guideline recommendations. Inputs included prevalence of mNSCLC, the proportion that tested positive for each genomic alteration, rebiopsy rates, time to test results, testing/medical costs, and costs of delaying care based on literature, public data, and expert opinion. Among 1,000,000 hypothetical publicly insured adult Canadians (382 with mNSCLC), the proportion of patients that tested positive for a genomic alteration with an approved targeted therapy was 38.0% for NGS and 26.1% for single-gene strategies. The estimated mean time to appropriate targeted therapy initiation was 5.1 weeks for NGS and 9.2 weeks for single-gene strategies. Based on literature, each week of delayed care cost CAD 406, translating to total mean per-patient costs of CAD 3480 for NGS and CAD 5632 for single-gene strategies. NGS testing with mNSCLC in current Canadian practice resulted in more patients with an identified mutation, shorter time to appropriate targeted therapy initiation, and lower total testing costs compared to single-gene strategies.

Real-World Persistence and Time to Next Treatment With Ibrutinib in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Including Patients at High Risk for Atrial Fibrillation or Stroke.

BACKGROUND: Atrial fibrillation (AF) is a recognized adverse consequence associated with all Bruton's tyrosine kinase inhibitors used to treat chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL); however, real-world time to discontinuation (TTD) and time to next treatment (TTNT) of CLL/SLL patients with a high baseline AF/stroke risk remain unknown. MATERIALS AND METHODS: Patients with CLL/SLL from a nationwide electronic health record-derived database (February 12, 2013-January 31, 2021) initiating first-line (1L) or second or later-line (2L+) treatment with ibrutinib or other regimens on or after February 12, 2014 (index date) were analyzed. Kaplan-Meier survival analysis was used to assess TTD and TTNT among all patients, patients with high AF risk (CHARGE-AF risk score ≥10.0%), and patients at high risk of stroke (CHA2DS2-VASc risk score ≥3 [females] or ≥2 [males]). RESULTS: In 1L/2L+, 2190/1851 patients received ibrutinib and 4388/4135, were treated with other regimens. Median TTD for ibrutinib was similar regardless of AF/stroke-related risk (1L: all patients, 15.7 months; high AF risk, 11.7 months; high stroke risk, 13.7 months; similar results in 2L+). Median TTNT was significantly longer for ibrutinib vs. other regimens (1L: not reached vs. 45.9 months; 2L+: not reached vs. 23.6 months; both P < .05), including among those with high AF/stroke risk. TTNT was similar between all patients and high-risk cohorts in 1L and 2L+ (all P > .05). CONCLUSION: This study highlights that elevated baseline AF/stroke-related risk does not adversely impact TTD and TTNT outcomes associated with ibrutinib use. Additionally, TTNT was significantly longer for patients treated with ibrutinib vs. other regimens.

Total cost of testing for genomic alterations associated with next-generation sequencing versus polymerase chain reaction testing strategies among patients with metastatic non-small cell lung cancer.

BACKGROUND: To assess the total cost of testing associated with next-generation sequencing (NGS) versus polymerase chain reaction (PCR) testing strategies among patients with metastatic non-small cell lung cancer (mNSCLC) from a Medicare and US commercial payer's perspective. MATERIALS AND METHODS: A decision tree model considered testing for genomic alterations in EGFR, ALK, ROS1, BRAF, KRAS, MET, HER2, RET, NTRK1 among patients with newly diagnosed mNSCLC using (1) liquid or tissue biopsy NGS tests, (2) exclusionary mutation (KRAS) test followed by sequential PCR tests, (3) sequential PCR tests, or (4) hotspot panel PCR tests. The alteration test sequence followed clinical guideline recommendations. Inputs based on literature, expert opinion, or assumptions included prevalence of mNSCLC, proportion of patients using each testing strategy (50% NGS [90% tissue, 10% liquid], 10% exclusionary, 10% sequential, 30% hotspot), proportion testing positive for each genomic mutation, rebiopsy rates, and costs for testing and associated medical care. Time to appropriate targeted therapy initiation and total costs were calculated for NGS, each PCR testing strategy, and all PCR strategies combined. RESULTS: Among a hypothetical plan of 1,000,000 members (75% commercial, 25% Medicare), 1,119 patients were estimated to have mNSCLC and be eligible for testing. Estimated mean time to appropriate targeted therapy was 2 weeks for NGS and 6 weeks for PCR (sequential: 9 weeks, exclusionary: 8 weeks, hotspot: 3 weeks). Mean per patient costs were $4,932 for NGS and $6,605 for PCR (exclusionary: $5,563, sequential: $6,263, hotspot: $7,066). Per patient costs were higher from a commercial perspective (NGS: $6,225; PCR: $8,430) relative to Medicare (NGS: $2,099; PCR: $2,646); nevertheless, NGS was the least costly testing strategy across plan types. CONCLUSION: NGS was associated with the fastest time to appropriate targeted therapy initiation and lowest total cost of testing compared to PCR testing strategies for newly diagnosed patients with mNSCLC.