Network meta-analysis of efficacy of ixazomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma.

OBJECTIVES: In the absence of head-to-head comparisons across relapsed/refractory multiple myeloma (RRMM) treatments following the approval of the oral proteasome inhibitor ixazomib, in combination with lenalidomide and dexamethasone (IRd), we conducted an indirect comparison of the efficacy of IRd relative to several RRMM therapies using Bayesian fixed-effects network meta-analysis (NMA) models. METHODS: Data for the NMA were obtained through a systematic literature review (conducted in June 2020), which identified randomized controlled trials (base case) and observational studies (extended network analysis) reporting overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). RESULTS: In the base case, IRd was associated with a significantly longer PFS than lenalidomide and dexamethasone (Rd), bortezomib monotherapy (V), dexamethasone (Dex), and pomalidomide and dexamethasone (Pom-dex), a significantly shorter PFS than daratumumab, lenalidomide, and dexamethasone (DRd), and a PFS comparable to elotuzumab, lenalidomide, and dexamethasone (ERd) and carfilzomib, lenalidomide, and dexamethasone (KRd). IRd was associated with a significantly longer OS than V, Dex, and Pom-dex, and an OS comparable to Rd, ERd, KRd, and DRd. The ORR of IRd was significantly higher than Rd, V, and Dex, significantly lower than KRd and DRd, and comparable to Pom-dex and ERd. The extended network analyses and sensitivity analyses were consistent with the base case. DISCUSSION: This NMA shows that IRd is relatively efficacious among RRMM treatments. Being an oral regimen, IRd is also convenient to manage. CONCLUSION: IRd could be a preferable treatment option for many patients with RRMM, particularly those seeking an efficacious and convenient therapeutic option.

Superior Outcomes With Continuing Tenofovir Versus Switching to Zidovudine in Second-Line Antiretroviral Therapy in Haiti.

We compared viral suppression rates between patients who continued tenofovir disoproxil fumarate (TDF)/lamivudine (3TC) vs switched to zidovudine (ZDV)/3TC in combination with a boosted protease inhibitor after failure of first-line efavirenz/TDF/3TC. We found higher rates of viral suppression with continued TDF/3TC compared with switching to ZDV/3TC.

Health care resource utilization and cost burden of hemophilia B in the United States.

Hemophilia B is a rare congenital blood disorder characterized by factor IX deficiency. Clinical profiles of hemophilia B range from mild to severe forms of the disease. The objective of this study was to characterize the economic burden associated with differing clinical profiles of hemophilia B from a US health system perspective. Using the IBM MarketScan database (June 2011-February 2019), a claims-based algorithm was developed to identify 4 distinct profiles (mild, moderate, moderate-severe, and severe) in adult males with hemophilia B based on the frequency of hemorrhage events and factor IX replacement claims. Mean annual health care resource use (HRU) and costs were statistically compared between patients with hemophilia B (N = 454) and 1:1 demographic-matched controls (N = 454), both overall and with stratification by clinical profile. Compared with matched controls, patients with hemophilia B had a significantly higher comorbidity burden (Charlson Comorbidity Index, mean ± standard deviation [SD]: 0.9 ± 1.7 vs 0.3 ± 0.9, P < .001). Across all clinical profiles, patients with hemophilia B had significantly higher HRU vs matched controls (mean ± SD: 0.3 ± 0.6 vs 0.1 ± 0.3 inpatient admissions; 0.6 ± 1.2 vs 0.2 ± 0.6 emergency department visits; 17.7 ± 22.9 vs 8.0 ± 11.0 outpatient visits; all P < .001). Annual total health care costs per patient among patients with hemophilia B were more than 25-fold higher vs matched controls (mean ± SD: $201 635 ± $411 530 vs $7879 ± $29 040, respectively, P < .001). Annual total health care costs per patient increased with increasing severity (mean ± SD: mild, $80 811 ± $284 313; moderate, $137 455 ± $222 021; moderate-severe, $251 619 ± $576 886; severe, $632 088 ± $501 270). The findings of this study highlight the substantial burden of illness associated with hemophilia B.

The Impact of Progression on Healthcare Resource Utilization and Costs Among Patients with High-Grade Non-Muscle Invasive Bladder Cancer After Bacillus Calmette-Guérin Therapy: A Retrospective SEER-Medicare Analysis.

INTRODUCTION: We evaluated the real-world healthcare resource utilization (HRU) and costs among patients with high-grade non-muscle invasive bladder cancer (HG-NMIBC) following Bacillus Calmette-Guérin (BCG) therapy. METHODS: Patients aged ≥ 65 years diagnosed with HG-NMIBC between 2008 and 2015 who received adequate BCG induction and were identified in the SEER-Medicare database. Those who received intravesical chemotherapy or radical cystectomy within 12 months of the last BCG induction dose, and had ≥ 6 months of data availability after treatment (index date), were included. Annualized HRU and mean medical costs (2020 United States dollars) were estimated and compared between patients with versus without progression. Inverse probability of treatment weighting was used to adjust for differences in baseline characteristics. RESULTS: Of 986 patients diagnosed with HG-NMIBC who met the inclusion criteria, 257 (26.1%) progressed; the mean ages were similar between patients who did and did not progress (77.6 vs. 77.0 years). The overall population had a mean of 0.96 [standard deviation (SD): 1.18] inpatient admissions, 6.47 (11.40) hospitalization days, 1.38 (2.19) emergency department (ED) visits, and 48.03 (44.97) outpatient visits per patient-year during the study period; total annualized costs per patient post-BCG were $39,102 ($44,244). Patients experiencing progression had significantly higher mean numbers of inpatient admissions [1.61 (SD 1.40) vs. 0.72 (0.99)], hospitalization days [11.77 (14.96) vs. 4.59 (9.29)], ED visits [2.34 (2.92) vs. 1.03 (1.76)], and outpatient visits [65.97 (44.72) vs. 41.63 (43.09)] per patient-year compared with patients without progression (all p < 0.05). Total mean annualized costs per patient after BCG among those who progressed [$65,668 (SD $53,943)] were more than double compared with patients who did not [$29,780 ($36,425)]. CONCLUSIONS: Existing treatments for HG-NMIBC after BCG therapy are associated with substantial HRU and medical costs, particularly after progression. Novel treatments and earlier detection are needed to reduce progression rates and associated costs in this difficult-to-treat population.

Concomitant Use of Psychotropic Medication With Stimulants for the Treatment of ADHD in Children and Adolescents: A Retrospective Insurance Claims Study in the United States.

Objective: To evaluate annual concomitant psychotropic medication use among stimulant-treated children/adolescents with ADHD. Method: Children/adolescents with ≥1 primary ADHD diagnosis who had received ≥30 days of stimulant medication were identified from insurance claims for each calendar year (2011-2014). Use of 15 psychotropic medications concomitantly with stimulants was evaluated and their prevalence in each year was calculated overall and by medication category for children (6-12 years) and adolescents (13-17 years). Results: Each year 133,354 to 157,303 children and 95,632 to 111,280 adolescents were included. Annual period prevalence of any concomitant psychotropic medication use was 22.9% to 25.0% for children and 25.2% to 28.2% for adolescents. The most common medication categories included selective serotonin reuptake inhibitors (children: 6.8%-7.9%; adolescents: 12.7%-14.9%), atypical antipsychotics (4.2%-5.4%; 5.3%-6.3%), and guanfacine extended release (5.1%-7.0%; 2.3%-3.6%). Conclusion: Around a quarter of children/adolescents with ADHD were prescribed psychotropic medication concomitant to stimulant treatment, although only 2 of the 15 medication classes studied were Food and Drug Administration (FDA)-approved for adjunctive use.

Comparative efficacy of first-line ceritinib and crizotinib in advanced or metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer: an adjusted indirect comparison with external controls.

Objective: In the absence of head-to-head trials, this study indirectly compared progression free survival (PFS) and overall survival (OS) between ceritinib and crizotinib among patients with previously untreated advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).Methods: A matching-adjusted indirect comparison method was implemented to adjust for cross-trial differences in patient characteristics between ASCEND-4 and PROFILE 1014 trials. Patient-level data from ASCEND-4 and published summary data from PROFILE 1014 were used. Patients in ASCEND-4 were reweighted to match average baseline characteristics (i.e. age, sex, race, tumor histology, ECOG score, smoking status, extent of disease, and presence of brain metastases) reported for PROFILE 1014 patients using propensity score weighting. PFS and OS were then compared between balanced populations.Results: ASCEND-4 included more current smokers (8.0% vs 4.4%) and fewer patients under the age of 65 years (78.5% vs 84.0%) compared to PROFILE 1014. After matching, these and all other patient characteristics were balanced between the two trial populations. Compared to crizotinib, ceritinib was associated with a significantly longer PFS (hazard ratio [95% confidence interval] (HR [CI]) = 0.64 [0.47-0.87]; median PFS: 25.2 vs 10.8 months, log-rank p-value = 0.003). OS did not differ significantly, with a HR of 0.82 [0.54-1.27] for ceritinib compared to crizotinib.Conclusions: In the adjusted indirect comparison with external controls, the second generation ALK inhibitor, ceritinib, was associated with a significantly prolonged PFS compared to crizotinib as first-line treatment for ALK-positive NSCLC.

Monitoring for and Characterizing Crizotinib Progression: A Chart Review of ALK-Positive Non-Small Cell Lung Cancer Patients.

INTRODUCTION: Crizotinib is recommended as first-line therapy for ALK-positive non-small cell lung cancer (NSCLC), but within a year of treatment initiation many patients develop resistance. With the recent approval of second-generation ALK inhibitors, this study assessed how physicians monitor for and diagnose progression and how they alter treatment following progression on crizotinib. METHODS: A panel of oncologists from the United States were surveyed regarding their monitoring practices and criteria for diagnosing progression on crizotinib. The physicians also retrospectively provided data (March-June 2016) from the medical charts of their adult patients with locally advanced or metastatic ALK-positive NSCLC who progressed on crizotinib after the approval (April 2014) of the first second-generation ALK inhibitor, ceritinib. RESULTS: A total of 28 physicians responded to the survey. Data was abstracted on 74 patients. In the physician survey, most physicians (71%) reported monitoring for radiographic progression every 3-4 months. When new lesions were detected, physician response varied. Following a symptomatic isolated lesion, most physicians (75%) would add local therapy and resume crizotinib. Following multiple symptomatic lesions, 96% and 64% of physicians would switch to a new therapy depending on whether the lesions were extracranial or isolated to the brain, respectively. For the patient cohort, physician-defined progression on crizotinib was diagnosed after a median of 10 months, and within 30 days of diagnosis, 86% of patients discontinued crizotinib. Among all patients who discontinued crizotinib, 77% switched to ceritinib, 14% to chemotherapy, and 1% to alectinib. The remaining 7% did not receive additional systemic antineoplastic therapy. CONCLUSION: The findings from this physician survey and retrospective chart review study suggest that physician response to the development of new lesions in crizotinib-treated ALK-positive NSCLC patients varies with location and extent of the lesions. Once patients were considered to have progressed, most of them were immediately switched to ceritinib. FUNDING: Novartis Pharmaceuticals Corporation.

Treatment Patterns and Early Outcomes of ALK-Positive Non-Small Cell Lung Cancer Patients Receiving Ceritinib: A Chart Review Study.

INTRODUCTION: This study aimed to provide the first real-world description of the characteristics, treatments, dosing patterns, and early outcomes of patients with ALK-positive non-small cell lung cancer (NSCLC) who received ceritinib in US clinical practice. METHODS: US oncologists provided data from medical charts of adult patients diagnosed with locally advanced or metastatic ALK-positive NSCLC who received ceritinib following crizotinib. Patient characteristics, treatment patterns, ceritinib dosing, early outcomes, and occurrence of gastrointestinal adverse events (AEs) by dose and instructions on food intake were assessed, and Kaplan-Meier analysis was used to describe clinician-defined progression-free survival (PFS) on ceritinib. RESULTS: Medical charts of 58 ALK-positive NSCLC patients treated with ceritinib were reviewed (median age 63 years; 41% male; 21% with prior chemotherapy experience). At ceritinib initiation, 44 patients had multiple distant metastases, most commonly in the liver (60%), bone (53%), and brain (38%). Initial ceritinib dose varied: 71% received 750 mg, 19% 600 mg, and 10% 450 mg. Although median follow-up after ceritinib initiation was short (3.8 months), most patients achieved either a complete or partial response (69%) on ceritinib, regardless of metastatic sites present at initiation or initial dose. Median PFS on ceritinib was 12.9 months. 17% of patients had a gastrointestinal AE reported during follow-up. The majority of events occurred in patients instructed to fast; no patients instructed to take a lower dose of ceritinib with food reported gastrointestinal AEs. CONCLUSION: These early findings of ceritinib use in clinical practice suggest that ceritinib is effective at treating crizotinib-experienced ALK-positive NSCLC patients, regardless of metastatic sites or initial dose, and dosing ceritinib with food may lead to fewer gastrointestinal AEs. Future studies with larger sample size and longer follow-up are warranted, including an ongoing randomized trial to assess the gastrointestinal tolerability of ceritinib 450 and 600 mg with low-fat meals. FUNDING: Novartis Pharmaceutical Corporation.