Purpose The main objective was to quantify any potential differences in pharmacokinetic (PK) parameters (AUC and C max ) between RTXM83, a proposed rituximab biosimilar, and its reference product, using a population PK model approach. Methods Rituximab PK and PD data were obtained from a randomized, double-blind, phase III clinical study (RTXM83-AC-01-11) in patients with diffuse large B-cell lymphoma (DLBCL) that received 375 mg/m 2 intravenous RTXM83 or its reference product with CHOP regimen, every 3 weeks, for six cycles. Rituximab levels were quantified by Meso Scale Discovery assay. PK analysis was performed using NONMEM 7.3.0. The effect of disease and patient covariates on RXTM83 PK was investigated. Model was evaluated using visual predictive check and non-parametric bootstrap. Results In total, 251 DLBCL patients (127 and 124 in RXTM83-CHOP and rituximab-CHOP arms, respectively) and 5341 serum concentrations (2703 for RXTM83 and 2638 for rituximab, respectively) were available for the population PK analysis. The volume of distribution of the central compartment (V 1 ) and clearance of RXTM83 were estimated at 3.19 L and 12.5 mL/h, respectively. Body surface area allowed to explain the interindividual variability for V 1 . A statistical analysis showed that systemic exposure (AUC and C max ) of RTXM83 was similar to rituximab. The 90% confidence intervals for all pairwise comparisons were within the predefined bioequivalence interval of 0.80-1.25. PD similarity of B-cell depletion and recovery was also observed. Conclusions The time course of RTXM83 was well characterized by the model developed. The systemic exposure of RTXM83 and its associated variability were similar to those for rituximab reference in DLBCL patients, demonstrating PK similarity. The PD similarity of RTXM83 and rituximab reference product was also demonstrated.

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Background MB02 (bevacizumab biosimilar) showed similar structural, functional, and pharmacokinetic properties to reference bevacizumab (Avastin ® ; EU-bevacizumab). Objectives To confirm clinical similarity between MB02 and EU-bevacizumab, a comparability study was undertaken in the first-line treatment of stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC).Patients and Methods This multinational, double-blind, randomized, phase III study (STELLA) compared MB02 or EUbevacizumab (15 mg/kg) administered with chemotherapy (paclitaxel 200 mg/m 2 and carboplatin AUC6) on Day 1 of every 3-week cycle for 6 cycles (Week 18), followed by MB02/EU-bevacizumab in blinded monotherapy until disease progression, unacceptable toxicity, death, withdrawal of consent or end of study (Week 52). The primary efficacy endpoint was objective response rate (ORR) evaluated by an independent radiological review committee (IRC) at Week 18 (intent-to-treat population). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety and immunogenicity. Results A total of 627 subjects were randomized 1:1 to MB02 (n = 315) or EU-bevacizumab (n = 312). ORR, assessed by the IRC at Week 18, was comparable in MB02 (40.3%) and EU-bevacizumab (44.6%) groups. ORR risk ratio of 0.910 (90% CI 0.780 to 1.060; 95% CI 0.758 to 1.092) and ORR risk difference of −4.02 (90% CI −10.51 to 2.47; 95% CI −11.76 to 3.71) were within the similarity predefined margins. There were no significant differences between MB02 and EU-bevacizumab groups in median PFS (36.0 vs 37.3 weeks, respectively; HR 1.187; 95% CI 0.98 to 1.44) and median OS (not achieved; HR 1.108; 95% CI: 0.83 to 1.49) at the end of study. The safety profile of MB02 and EU-bevacizumab regarding nature, frequency and severity of the adverse events (AE) was comparable. The most frequent grade ≥3 investigational-product-related AEs were hypertension and anemia, with a difference between treatment groups of <5%. Anti-drug antibodies (ADA) and neutralizing ADA (NAb) incidence were similar in both treatment groups. Conclusion MB02 demonstrated similar efficacy to EU-bevacizumab, in combination with carboplatin and paclitaxel, in subjects with advanced non-squamous NSCLC, with comparable safety and immunogenicity profiles. Clinical trial registration EudraCT No. 2017-001769-26; ClinicalTrials.gov: NCT03296163.The members of the STELLA study investigators are listed in Online Resource 1 and in the Acknowledgements section.Extended author information available on the last page of the article care costs [1,2]. Avastin ® , the reference bevacizumab, has been approved for use in many cancer indications and settings, including first-line treatment of advanced NSCLC in combination with other chemotherapeutic agents [3,4]. Several international guidelines recommend the use of bevacizumab in association with chemotherapy in first-line and maintenance settings in advanced NSCLC [5,6]. In addition, recent evidence points to novel combinations of bevacizumab with new molecular therap...

We report the case of a 74-year-old woman with elevated liver enzyme levels in whom abdominal sonographic examination revealed a diffusely heterogeneous liver parenchyma and multiple hypoechoic subcentimetric splenic nodules. Contrast-enhanced sonography (CEUS) revealed that the splenic focal lesions did not enhance. CT examination revealed a low-density, multinodular pattern both in the liver and in the spleen. Core biopsy of 1 hepatic nodule revealed noncaseating epithelioid cell granuloma, and the patient was diagnosed with systemic sarcoidosis. CEUS has shown to be useful in the diagnosis of focal hepatic lesions, but studies referring to splenic lesions are lacking.

CT-1P tono-pachymeter underestimates CCT measurements compared to Scheimpflug system, AS-OCT device, and USP. Mean CCT among USP, Pentacam and AS-OCT were comparable and had significant linear correlations. In clinical practice, these three modalities could be interchangeable in healthy patients.