Real-world evidence of obinutuzumab and venetoclax in previously treated patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.

Venetoclax-obinutuzumab (Ven-O) is frequently administered off-label in relapsed/refractory (r/r) CLL/SLL where venetoclax-rituximab is the approved regimen. We conducted this retrospective, real-world study to evaluate Ven-O in r/r CLL/SLL. Between 7/2019 and 6/2022, 40 patients with r/r CLL/SLL on Ven-O were included. The median age was 72, 28.2% had TP53 mutation and/or 17p deletion, median number of prior therapies was 1 (range, 1-6), and 55% had prior BTK inhibitor exposure. The overall response rate was 90% (complete response [CR] or CR with incomplete marrow recovery in 27.5% and partial response in 62.5%) of patients, and the 2-year progression-free survival was 81.2% (95% CI, 69.5-94.8). Therapy was well tolerated. No laboratory or clinical TLS occurred with venetoclax (Howard criteria). One (3%) patient experienced laboratory TLS with obinutuzumab initiation. In summary, this retrospective cohort study demonstrated that Ven-O achieves frequent, durable responses and can be safely administered in r/r CLL/SLL.

Survival outcomes associated with corticosteroid use before chemoimmunotherapy in patients with advanced lung cancer.

BACKGROUND: How corticosteroid use affects treatment response to chemotherapy and immune-checkpoint inhibitors (CICPIs) remains unknown. We assessed how systemic corticosteroid exposure before CICPI modifies the effect of CICPI on outcomes among patients with metastatic non-small cell lung cancer (mNSCLC) or extensive-stage small-cell lung cancer (ES-SCLC). METHODS: We conducted a retrospective cohort study using electronic health records to examine patients with mNSCLC or ES-SCLC who received chemotherapy (CT) between 1st April 2015 and 31st January 2018 or CICPI between 1st February 2018 and 31st August 2019. We excluded those with an actionable driver mutation. Baseline corticosteroid use was defined as systemic corticosteroids within 28 days before the initiation of CT or CICPI, not including premedications. Coprimary outcomes included overall survival (OS), real-world progression (rwP), and real-world progression-free survival (rwPFS) in CICPI-treated corticosteroid users versus non-users. We used inverse probability of treatment weighting (IPW) to adjust for potential confounding. RESULTS: The cohort of 316 patients (median [interquartile range] age, 67 [61-73] years; 156 [49%] male) included 228 CT-treated and 88 CICPI-treated patients. After applying IPW, characteristics were well-balanced between the CT and CICPI groups, and steroid users and non-users. Using CT-treated steroid non-users as a common comparator, CICPI-treated steroid users were as likely as CICPI-treated steroid non-users to die (users IPW hazard ratio [HR] = 0.67, 95% CI = 0.35-1.28 versus non-users IPW-HR = 0.88, 95% C = I0.55-1.42; p = 0.49), have rwP (IPW-HR = 0.35, 95% C = I0.12-0.99 versus IPW-HR = 0.41, 95% C = I0.24-0.70; p = 0.77), or experience rwPFS (IPW-HR = 0.56, 95% C = I0.29-1.09 versus IPW-HR = 0.69, 95% CI0.46-1.03; p = 0.59). CONCLUSION: Corticosteroid use before CICPIs was not associated with worse outcomes, suggesting that corticosteroids should be used with CICPIs when indicated.

Predictors of Hip Fracture Despite Treatment with Bisphosphonates among Frail Older Adults.

OBJECTIVES: Bisphosphonates are effective at preventing hip fractures among older adults, yet many patients still fracture while on treatment and may benefit from additional preventive interventions. Little data are specifically available to target such efforts among bisphosphonate users. We aimed to identify predictors of hip fracture unique to frail older adults initiating pharmacologic treatment for osteoporosis. DESIGN: Retrospective cohort using 2008-2013 linked national Minimum Data Set assessments, Medicare claims, and nursing home (NH) facility data. SETTING: NHs in the United States. PARTICIPANTS: Long-stay NH residents 65 years or older who initiated treatment with a bisphosphonate (N = 17 753). Estimates for bisphosphonate initiators were contrasted with those for calcitonin initiators (control group; N = 5348). MEASUREMENTS: Hospitalized hip fracture outcomes were measured using Part A claims. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for 36 a priori selected potential predictors. RESULTS: The mean (SD) age of the study population was 84 (8) years, 85% were women, and 51% had moderate to severe cognitive impairment. Predictors associated with a higher risk of hip fracture despite bisphosphonate use included age 75 years or older to 85 years (vs ≥65 to <75 y; HR = 1.25; 95% CI = 1.02-1.55), female sex (HR = 1.33; 95% CI = 1.06-1.67), white race (vs black race (HR = 1.87; 95% CI = 1.36-2.58), and body mass index = 18.5-24.9 (vs ≥30; HR = 1.93; 95% CI = 1.53-2.42). Independent ability to transfer (vs total dependence; HR = 3.11; 95% CI = 1.83-5.30) and occasional urinary incontinence (vs frequent; HR = 1.45; 95% CI = 1.18-1.78) were also important predictors. Dementia, diabetes, psychoactive drug use, and other characteristics were not associated with post-prescribing hip fracture. Predictors did not differ between bisphosphonate and calcitonin users. CONCLUSION: Predictors of hip fracture among frail older adults did not differ between those who were new users of bisphosphonates vs calcitonin. Given the absence of risk factors unique to bisphosphonate users, targeting of fracture prevention efforts should extend beyond pharmacologic therapy to include existing nonpharmacologic therapies, particularly fall prevention strategies. J Am Geriatr Soc 68:256-260, 2020.

Exogenous supplementation of antithrombin III in adult and pediatric patients receiving extracorporeal membrane oxygenation.

BACKGROUND: Antithrombin III deficiency can occur with heparin anticoagulation during extracorporeal membrane oxygenation leading to heparin resistance. Antithrombin III supplementation has been shown to improve anticoagulation; however, there is no consensus on appropriate administration. We described the effect of antithrombin III supplementation on coagulation parameters in adult and pediatric extracorporeal membrane oxygenation patients. METHODS: We conducted a retrospective cohort study using electronic medical records of patients who received ⩾1 dose of antithrombin III during extracorporeal membrane oxygenation while on continuous heparin. Endpoints included the change in anti-Xa levels and antithrombin III activity at -6 versus 6 h relative to antithrombin III supplementation, and heparin infusion rates at 6 versus 12 h after antithrombin III supplementation. RESULTS: Eighteen patients receiving 36 antithrombin III administrations were analyzed. Mean (standard deviation) anti-Xa values at -6 versus 6 h were 0.15 (0.07) versus 0.24 (0.15) IU/mL (p-value: 0.250) for pediatrics and 0.19 (0.22) versus 0.31 (0.27) IU/mL (p-value: 0.052) for adults. Mean (standard deviation) plasma antithrombin III activity at the same intervals were 32% (14.2%) versus 66.8% (25.1%; p-value: 0.062) for pediatrics and 30.3% (14%) versus 52.8% (8.1%; p-value: 0.094) for adults. Mean (standard deviation) heparin rates at 6 versus 12 h after antithrombin III for pediatrics were 23.6 (6) versus 23.5 (6.5) units/kg/h (p-value: 0.728), and 15.3 (6.6) versus 13.5 (8) units/kg/h (p-value: 0.188) for adults. CONCLUSION: Administration of antithrombin III improved anti-Xa levels in both populations, however, did not significantly reduce heparin rates. Our findings suggest that the use of antithrombin III restores heparin responsiveness in patients with low antithrombin III activity and low anti-Xa activity.