The antiretroviral efficacy of highly active antiretroviral therapy and plasma nevirapine concentrations in HIV-TB co-infected Indian patients receiving rifampicin based antituberculosis treatment

Abstract Background Rifampicin reduces the plasma concentrations of nevirapine in human immunodeficiency virus (HIV) and tuberculosis (TB) co-infected patients, who are administered these drugs concomitantly. We conducted a prospective interventional study to assess the efficacy of nevirapine-containing highly active antiretroviral treatment (HAART) when co-administered with rifampicin-containing antituberculosis treatment (ATT) and also measured plasma nevirapine concentrations in patients receiving such a nevirapine-containing HAART regimen. Methods 63 cases included antiretroviral treatment naïve HIV-TB co-infected patients with CD4 counts less than 200 cells/mm3 started on rifampicin-containing ATT followed by nevirapine-containing HAART. In control group we included 51 HIV patients without tuberculosis and on nevirapine-containing HAART. They were assessed for clinical and immunological response at the end of 24 and 48 weeks. Plasma nevirapine concentrations were measured at days 14, 28, 42 and 180 of starting HAART. Results 97 out of 114 (85.1%) patients were alive at the end of 48 weeks. The CD4 cell count showed a mean increase of 108 vs.113 cells/mm3 (p=0.83) at 24 weeks of HAART in cases and controls respectively. Overall, 58.73% patients in cases had viral loads of less than 400 copies/ml at the end of 48 weeks. The mean (± SD) Nevirapine concentrations of cases and control at 14, 28, 42 and 180 days were 2.19 ± 1.49 vs. 3.27 ± 4.95 (p = 0.10), 2.78 ± 1.60 vs. 3.67 ± 3.59 (p = 0.08), 3.06 ± 3.32 vs. 4.04 ± 2.55 (p = 0.10) respectively and 3.04 μg/ml (in cases). Conclusions Good immunological and clinical response can be obtained in HIV-TB co-infected patients receiving rifampicin and nevirapine concomitantly despite somewhat lower nevirapine trough concentrations. This suggests that rifampicin-containing ATT may be co administered in resource limited setting with nevirapine-containing HAART regimen without substantial reduction in antiretroviral effectiveness. Larger sample sized studies and longer follow-up are required to identify populations of individuals where the reduction in nevirapine concentration may result in lower ART response or shorter response duration

Beta-adrenergic antagonist tolerance in amyloid cardiomyopathy

Background: Beta-adrenergic antagonists or blockers (BB) are a cornerstone of cardiac therapy for multiple indications. However, BB are considered relatively contraindicated in amyloid cardiomyopathy due to poor tolerance. This intolerance is hypothesized to be due to concomitant neuropathy and significant restrictive cardiomyopathy. This study analyzes the incidence and characteristics of BB tolerance in patients with amyloid cardiomyopathy. Methods: Through a single-center retrospective chart review, patients with amyloid cardiomyopathy, confirmed by endomyocardial biopsy or technetium-99 pyrophosphate scan, were identified and clinical data was collected. Statistical methods included Chi-square test and two sample Results: Of 135 cardiac amyloidosis patients, 27 patients (20.0%) had no BB use, 56 patients (41.5%) were current BB users, and 52 patients (38.5%) were prior BB users. The most frequent indications for BB use were heart failure, hypertension, coronary artery disease, and arrhythmia. The most common reason for stopping BB therapy was hypotension (62.8%) followed by fatigue, bradycardia, and orthostasis. Neurologic symptoms at the initial BB prescription or most recent evaluation were not significantly different between current and prior BB users. Their cardiovascular profiles were similar by ejection fraction, wall thickness, troponin I, and brain natriuretic peptide. There was no association for BB discontinuation based on amyloid subtype, sex, or race. Conclusion: The majority of patients with amyloid cardiomyopathy were prescribed BB, and over half of these patients still tolerated BB therapy. Current and prior BB users had similar profiles from a cardiovascular and neurologic perspective, with no association identified to predict BB discontinuation

Multiple Myeloma: Clinical Updates from the American Society of Clinical Oncology Annual Scientific Symposium 2020

The novel clinical data for plasma cell neoplasms (smoldering myeloma, multiple myeloma, and AL amyloidosis) that were presented in the 2020 American Society of Clinical Oncology virtual scientific symposium are summarized here. Data from large phase-3 studies (CASSIOPEIA, ENDURANCE, and TOURMALINE-MM4 trials) and phase-2 studies (SWOG 1211, GMMG CONCEPT trials) for newly diagnosed multiple myeloma patients who are eligible for autologous stem cell transplantation are described. Updates from previous important studies for multiple myeloma (STaMINA) along with studies on three different chimeric antigen receptor (CAR-) T cell products are also described. Results of clinical studies involving the use of anti-myeloma drugs with novel mechanisms of action such as immunoconjugates, selinexor, venetoclax, monoclonal antibodies, and data on minimal residual disease (MRD) are discussed. These data provide an overview of the efficacy and safety of the various treatments in multiple myeloma and could lead to changes in our clinical practice, which could pave the path for a “cure” in myeloma

Neutrophil lymphocyte ratio and duration of prior anti-angiogenic therapy as biomarkers in metastatic RCC receiving immune checkpoint inhibitor therapy

Abstract Background There is an unmet need to determine factors predictive of clinical benefit, to guide therapeutic sequencing and selection in metastatic RCC (mRCC). We evaluated clinical factors such as the neutrophil lymphocyte ratio (NLR) and duration of prior anti-vascular endothelial growth factor (VEGF) inhibitors, as predictors of response rate, progression free survival (PFS) and overall survival (OS) in mRCC patients treated with immune checkpoint inhibitor (ICI). Methods Regulatory approval was obtained. A single center retrospective chart review of mRCC patients at Karmanos Cancer Institute, treated with ICI based therapy (PD-1/PD-L1 inhibitors) was conducted. Data were collected on demographics, smoking status, prognostic scoring (Memorial Sloan Kettering and Heng criteria), NLR pretherapy, post 1 and 4 doses of ICI, and duration of prior anti-VEGF therapy ≥6 months or <6. Results 42 patients were evaluated with median age of 61 years (range, 24-85). Pretherapy NLR < 3 and ≥3 was seen in 19 (45%) and 23 (55%) patients, respectively. 24 (57%) and 18 (43%) patients had prior anti-VEGF inhibitors for a duration of ≥6 months and <6 months, respectively. 12 (29%), 22 (52%) and 8 (19%) patients had favorable, intermediate and poor risk disease based on Heng criteria, respectively. Multivariable analysis showed pretherapy NLR ≥3 was predictive of shorter PFS and OS when treated with ICI with median 3.08 months and 13.50 months, respectively, versus 15.57 months and not reached for NLR < 3 (adjusted p-values =0.003 and 0.025, respectively). Prior anti-VEGF therapy <6 months was predictive of increased likelihood of benefit from ICI therapies (adjusted p = 0.028). The median PFS was 3.72 months and 14.33 months, respectively, in cases with prior anti-VEGF therapy for ≥6 months and <6 months. Conclusion Pretherapy NLR <3 and duration of prior anti-VEGF therapy of <6 months, are independent statistically significant predictors of longer PFS and OS with ICI therapy in mRCC. Validation is required in a larger sample size with multi-institutional collaboration

Functional Impairments of Amyloidosis Patients: Physical Therapy Assessment

Amyloidosis is a rare, systemic disease that can result in significant functional impairment. Specific guidelines for the rehabilitation assessment of amyloidosis patients have yet to be established. The purpose of this study was to identify functional deficits and assess differences based on disease type, organ involvement, age, and gender of patients with amyloidosis. Materials and Methods: The multidisciplinary Comprehensive Amyloidosis Clinic (CAC) at Ohio State University (OSU) has developed structured assessment guidelines for amyloidosis patients. A retrospective, single-institution review of patients assessed in CAC between December 2017 and April 2020 was performed. Outcome measure data from the Timed Up and Go (TUG), 30 s sit-to-stand, and physical function portion of the SF 36 were gathered by chart review. Comparisons were made between CAC patient scores and normative data. Kruskal–Wallis tests were used to compare scores across the disease types (light chain, transthyretin wild-type, and hereditary variant transthyretin) and the Mann–Whitney U test was used for pairwise comparisons within disease types and cardiac involvement. Linear regression models were used to assess associations between patient characteristics (including age, gender, disease type, and cardiac involvement) and performance scores. Results: Data from sixty-four patients was evaluated. On the 30-s sit-to-stand test, patients with light chain amyloidosis performed 3.32 fewer repetitions than patients with transthyretin wild-type, p = 0.03. Patients with cardiac involvement had 2.55 fewer repetitions than patients without cardiac involvement, p = 0.03. Older patients were found to have slower TUG performance, and a 10-year increase in age was associated with an 11% increase in TUG scores. Conclusions: Findings indicate patients with light chain amyloidosis and patients with cardiac involvement, when compared to other amyloidosis patients, present with more physical impairments

Improvement in Post-Autologous Stem Cell Transplant Survival of Multiple Myeloma Patients: A Long-Term Institutional Experience

Multiple myeloma (MM) represents 1.8% of all new cancer cases in the U.S. While not curable, advances in treatment, including autologous stem cell transplant (ASCT) and maintenance therapy, have dramatically improved progression-free survival (PFS) and overall survival (OS). We performed a retrospective survival analysis on newly diagnosed MM (NDMM) patients receiving ASCT from 1992&ndash;2016 at the Ohio State University. A total of 1001 consecutive NDMM patients were eligible. Patients were split into five groups based on historic changes in novel agents for the treatment of MM. Across the years (1992&ndash;2016), there was a statistically significant improvement in both PFS (p &lt; 0.01) and OS (p &lt; 0.01). Significant improvements in both PFS and OS were seen in patients &le;65 years (p &lt; 0.001 and p = 0.002) and &gt;65 years old (p &lt; 0.001 and p = 0.001), respectively. Improved PFS and OS were seen in both standard-risk (p &lt; 0.001 and p &lt; 0.001) and high-risk patients (p &lt; 0.001 and p = 0.019). The post-transplant response showed statistically significant improvement across the years (p &lt; 0.01). Survival rates for NDMM patients have significantly improved primarily due to the inclusion of novel therapies and post-ASCT maintenance

Early versus Late Discontinuation of Maintenance Therapy in Multiple Myeloma

Maintenance therapy after autologous stem cell transplant (ASCT) in multiple myeloma (MM) is the standard treatment and recommended to be continued until disease progression. However, in the real world, patients discontinue treatment due to various reasons. We sought to determine the effect of early versus late discontinuation on survival outcomes in MM patients who underwent ASCT at The Ohio State University. We retrospectively reviewed 340 patients who underwent ASCT from 2005 to 2016 and received maintenance therapy for at least six months without progression. We compared the outcomes of patients who received maintenance for three years or less (early group) to the patients who continued maintenance beyond three years (late group). Lenalidomide (89%) and bortezomib (10%) were the most common agents used for maintenance chemotherapy. In Kaplan–Meier analysis, patients in the late group had prolonged progression-free (PFS) (p p < 0.001). The 5-year estimated OS in late group was 96% vs. 79% in the early group and 5-year PFS was 80% in late group vs. 50% in the early group. The most common reasons for discontinuation of maintenance in early group were adverse events (55.9%) and patient preference (22.5%). For the late group, it was disease progression (23.9%) and adverse events (14.3%). Fifty-five percent of patients in the late group were still on maintenance treatment at the last follow-up. Continuation of maintenance therapy was thus associated with improved outcomes, while adverse events prevented most patients from continuing treatment