Photobiomodulation therapy is able to decrease IL1B gene expression in an in vitro cellular model of hidradenitis suppurativa

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Meta-Analysis of Yield Response of Hybrid Field Corn to Foliar Fungicides in the U.S. Corn Belt

The use of foliar fungicides on field corn has increased greatly over the past 5 years in the United States in an attempt to increase yields, despite limited evidence that use of the fungicides is consistently profitable. To assess the value of using fungicides in grain corn production, random-effects meta-analyses were performed on results from foliar fungicide experiments conducted during 2002 to 2009 in 14 states across the United States to determine the mean yield response to the fungicides azoxystrobin, pyraclostrobin, propiconazole + trifloxystrobin, and propiconazole + azoxystrobin. For all fungicides, the yield difference between treated and nontreated plots was highly variable among studies. All four fungicides resulted in a significant mean yield increase relative to the nontreated plots (P \u3c 0.05). Mean yield difference was highest for propiconazole + trifloxystrobin (390 kg/ha), followed by propiconazole + azoxystrobin (331 kg/ha) and pyraclostrobin (256 kg/ha), and lowest for azoxystrobin (230 kg/ha). Baseline yield (mean yield in the nontreated plots) had a significant effect on yield for propiconazole + azoxystrobin (P \u3c 0.05), whereas baseline foliar disease severity (mean severity in the nontreated plots) significantly affected the yield response to pyraclostrobin, propiconazole + trifloxystrobin, and propiconazole + azoxystrobin but not to azoxystrobin. Mean yield difference was generally higher in the lowest yield and higher disease severity categories than in the highest yield and lower disease categories. The probability of failing to recover the fungicide application cost (ploss) also was estimated for a range of grain corn prices and application costs. At the 10-year average corn grain price of $0.12/kg ($2.97/bushel) and application costs of $40 to 95/ha, ploss for disease severity \u3c5% was 0.55 to 0.98 for pyraclostrobin, 0.62 to 0.93 for propiconazole + trifloxystrobin, 0.58 to 0.89 for propiconazole + azoxystrobin, and 0.91 to 0.99 for azoxystrobin. When disease severity was \u3e5%, the corresponding probabilities were 0.36 to 95, 0.25 to 0.69, 0.25 to 0.64, and 0.37 to 0.98 for the four fungicides. In conclusion, the high ploss values found in most scenarios suggest that the use of these foliar fungicides is unlikely to be profitable when foliar disease severity is low and yield expectation is high

Lenalidomide Maintenance with or without Prednisone in Newly Diagnosed Myeloma Patients: A Pooled Analysis

We conducted a pooled analysis of two phase III trials, RV-MM-EMN-441 and EMN01, to compare maintenance with lenalidomide-prednisone vs. lenalidomide in newly diagnosed transplant-eligible and -ineligible myeloma patients. Primary endpoints were progression-free survival, progression-free survival 2 and overall survival with both regimens. A secondary aim was to evaluate the impact of duration of maintenance on overall survival and on outcome after relapse. A total of 625 patients (lenalidomide-prednisone arm, n = 315; lenalidomide arm, n = 310) were analyzed. The median follow-up was 58 months. Median progression-free survival (25 vs. 19 months; p = 0.08), progression-free survival 2 (56 vs. 49 months; p = 0.9) and overall survival (73 months vs. NR; p = 0.08) were not significantly different between the two arms. Toxicity profiles of lenalidomide-prednisone and lenalidomide were similar, with the exception of neutropenia that was higher in the lenalidomide arm (grade ≥ 3: 9% vs. 19%, p < 0.001), without an increase in the rate of infections. Overall survival (median NR vs. 49 months, p < 0.001), progression-free survival from relapse (median 35 vs. 24 months, p = 0.004) and overall survival from relapse (median not reached vs. 41 months, p = 0.002) were significantly longer in patients continuing maintenance for ≥2 years. We showed that the addition of prednisone at 25 or 50 mg every other day (eod) to lenalidomide maintenance did not induce any significant advantage

Elevated lactate dehydrogenase has prognostic relevance in treatment-na\uefve patients affected by chronic lymphocytic leukemia with trisomy 12

Chronic Lymphocytic Leukemia (CLL) patients with +12 have been reported to have specific clinical and biologic features. We performed an analysis of the association between demographic; clinical; laboratory; biologic features and outcome in CLL patients with +12 to identify parameters predictive of disease progression; time to treatment; and survival. The study included 487 treatment-naive CLL patients with +12 from 15 academic centers; diagnosed between January 2000 and July 2016; and 816 treatment-na\uefve patients with absence of Fluorescence In Situ Hybridization (FISH) abnormalities. A cohort of 250 patients with +12 CLL followed at a single US institution was used for external validation. In patients with +12; parameters associated with worse prognosis in the multivariate model were high Lactate DeHydrogenase (LDH) and \u3b2-2- microglobulin and unmutated immunoglobulin heavy-chain variable region gene (IGHV). CLL patients with +12 and high LDH levels showed a shorter Progression-Free-Survival (PFS) (30 months vs. 65 months; p &lt; 0.001), Treatment-Free-Survival (TFS) (33 months vs. 69 months; p &lt; 0.001), Overall Survival (OS) (131 months vs. 181 months; p &lt; 0.001) and greater CLL-related mortality (29% vs. 11% at 10 years; p &lt; 0.001) when compared with +12 CLL patients with normal LDH levels. The same differences were observed in the validation cohort. These data suggest that serum LDH levels can predict PFS; TFS; OS and CLL-specific survival in CLL patients with +12

Choice of Frontline Tyrosine-Kinase Inhibitor and Early Events in Very Elderly Patients With Chronic Myeloid Leukemia in Chronic Phase: A "Campus CML" Study

Objectives: The study aimed to evaluate the utilization of frontline TKI therapy in a large cohort of elderly CP-CML patients. Methods: A retrospective analysis was conducted on 332 CP-CML patients aged 75 years or older among 1929 diagnosed from January 2012 to December 2019 followed at 36 participating Hematology Centers involved in the "Campus CML" project. Results: Among the patients analyzed, 85.8% received imatinib (IM) while 14.2% received second-generation TKIs (2G-TKI), 59.5% dasatinib, and 40.5% nilotinib. Most patients initiated IM at standard dose (67.3%) while 32.7% at reduced dose. A similar trend was observed with 2G-TKIs. The cumulative incidence of permanent TKI discontinuation at 12 months was 28.4%, primarily due to primary resistance (10.1%) and extra-hematologic toxicity (9.5%), with no significant difference between IM and 2G-TKI groups. Following the introduction of generic IM in Italy in 2018, IM usage increased significantly compared with 2G-TKIs. Conclusions: IM was in our Centers the preferred frontline therapy for older CP-CML patients, with increasing utilization after the introduction of generic formulations. However, 2G-TKIs are still used in a substantial proportion of patients, suggesting individualized physician assessments regarding patient suitability and expectations. Further investigation is needed to assess efficacy and safety of reduced TKI doses in this patient population

Survival Risk Scores for Real-Life Relapsed/Refractory Multiple Myeloma Patients Receiving Elotuzumab or Carfilzomib In Combination With Lenalidomide and Dexamethasone as Salvage Therapy: Analysis of 919 Cases Outside Clinical Trials

The present study aimed to develop two survival risk scores (RS) for overall survival (OS, SRSKRd/EloRd) and progression-free survival (PFS, PRSKRd/EloRd) in 919 relapsed/refractory multiple myeloma (RRMM) patients who received carfilzomib, lenalidomide, and dexamethasone (KRd)/elotuzumab, lenalidomide, and dexamethasone (EloRd). The median OS was 35.4 months, with no significant difference between the KRd arm versus the EloRd arm. In the multivariate analysis, advanced ISS (HR = 1.31; P = 0.025), interval diagnosis–therapy (HR = 1.46; P = 0.001), number of previous lines of therapies (HR = 1.96; P &lt; 0.0001), older age (HR = 1.72; P &lt; 0.0001), and prior lenalidomide exposure (HR = 1.30; P = 0.026) remained independently associated with death. The median PFS was 20.3 months, with no difference between the two strategies. The multivariate model identified a significant progression/death risk increase for ISS III (HR = 1.37; P = 0.002), &gt;3 previous lines of therapies (HR = 1.67; P &lt; 0.0001), older age (HR = 1.64; P &lt; 0.0001), and prior lenalidomide exposure (HR = 1.35; P = 0.003). Three risk SRSKRd/EloRd categories were generated: low-risk (134 cases, 16.5%), intermediate-risk (467 cases, 57.3%), and high-risk categories (213 cases, 26.2%). The 1- and 2-year OS probability rates were 92.3% and 83.8% for the low-risk (HR = 1, reference category), 81.1% and 60.6% (HR = 2.73; P &lt; 0.0001) for the intermediate-risk, and 65.5% and 42.5% (HR = 4.91; P &lt; 0.0001) for the high-risk groups, respectively. Notably, unlike the low-risk group, which did not cross the median timeline, the OS median values were 36.6 and 18.6 months for the intermediate- and high-risk cases, respectively. Similarly, three PRSKRd/EloRd risk categories were engendered. Based on such grouping, 338 (41.5%) cases were allocated in the low-, 248 (30.5%) in the intermediate-, and 228 (28.0%) in the high-risk groups. The 1- and 2-year PFS probability rates were 71.4% and 54.5% for the low-risk (HR = 1, reference category), 68.9% and 43.7% (HR = 1.95; P &lt; 0.0001) for the intermediate-risk, and 48.0% and 27.1% (HR = 3.73; P &lt; 0.0001) for the high-risk groups, respectively. The PFS median values were 29.0, 21.0, and 11.7 months for the low-, intermediate-, and high-risk cases. This analysis showed 2.7- and 4.9-fold increased risk of death for the intermediate- and high-risk cases treated with KRd/EloRd as salvage therapy. The combined progression/death risks of the two categories were increased 1.3- and 2.2-fold compared to the low-risk group. In conclusion, SRSKRd/EloRd and PRSKRd/EloRd may represent accessible and globally applicable models in daily clinical practice and ultimately represent a prognostic tool for RRMM patients who received KRd or EloRd

Determinants of frontline tyrosine kinase inhibitor choice for patients with chronic-phase chronic myeloid leukemia: A study from the Registro Italiano LMC and Campus CML

BackgroundImatinib, dasatinib, and nilotinib are tyrosine kinase inhibitors (TKIs) approved in Italy for frontline treatment of chronic-phase chronic myeloid leukemia (CP-CML). The choice of TKI is based on a combined evaluation of the patient's and the disease characteristics. The aim of this study was to analyze the use of frontline TKI therapy in an unselected cohort of Italian patients with CP-CML to correlate the choice with the patient's features. MethodsA total of 1967 patients with CP-CML diagnosed between 2012 and 2019 at 36 centers throughout Italy were retrospectively evaluated; 1089 patients (55.4%) received imatinib and 878 patients (44.6%) received a second-generation (2G) TKI. ResultsSecond-generation TKIs were chosen for most patients aged &lt;45 years (69.2%), whereas imatinib was used in 76.7% of patients aged &gt;65 years (p &lt; .001). There was a predominant use of imatinib in intermediate/high European long-term survival risk patients (60.0%/66.0% vs. 49.7% in low-risk patients) and a limited use of 2G-TKIs in patients with comorbidities such as hypertension, diabetes, chronic obstructive pulmonary disease, previous neoplasms, ischemic heart disease, or stroke and in those with &gt;3 concomitant drugs. We observed a greater use of imatinib (61.1%) in patients diagnosed in 2018-2019 compared to 2012-2017 (53.2%; p = .002). In multivariable analysis, factors correlated with imatinib use were age &gt; 65 years, spleen size, the presence of comorbidities, and &amp; GE;3 concomitant medications. ConclusionsThis observational study of almost 2000 cases of CML shows that imatinib is the frontline drug of choice in 55% of Italian patients with CP-CML, with 2G-TKIs prevalently used in younger patients and in those with no concomitant clinical conditions. Introduction of the generic formulation in 2018 seems to have fostered imatinib use