Tocilizumab Dosing for Management of T Cell-Engaging Bispecific Antibody-Related CRS in Patients With R/R B-Cell NHL.

The recent surge in T-cell-engaging and chimeric antigen receptor (CAR) T-cell therapies is changing the landscape of cancer therapy. Cytokine release syndrome (CRS) is a systemic inflammatory response syndrome that is a well-known complication of these therapies, of which interleukin-6 (IL-6) is a key mediator. Tocilizumab, an IL-6 receptor (IL-6R) antagonist, is approved for the management of CAR T-cell therapy-induced CRS in adults and in pediatric patients aged ≥ 2 years old.

Ethnic Sensitivity Assessment of Mosunetuzumab Pharmacokinetics and Pharmacodynamics in Chinese Patients With Relapsed or Refractory Follicular Lymphoma.

Mosunetuzumab, a CD20 × CD3 T-cell-engaging bispecific antibody, redirects T cells to eliminate malignant B cells. The purpose of YO43555 was to assess the pharmacokinetics (PK), safety, tolerability, and efficacy of mosunetuzumab as a single agent in Chinese patients with relapsed/refractory follicular lymphoma (R/R FL). The impact of ethnicity/region on the PK disposition of mosunetuzumab was assessed by non-compartmental analysis (NCA) as well as a population PK (popPK) approach.

Persistent fatty acid catabolism during plant oil synthesis.

Plant lipids are an essential energy source for diets and are a sustainable alternative to petroleum-based fuels and feedstocks. Fatty acid breakdown during seed germination is crucial for seedling establishment but unexpected during seed filling. Here, we demonstrate that the simultaneous biosynthesis and degradation of fatty acids begins early and continues across all phases of oil filling and throughout the photoperiod.

Mosunetuzumab plus Pola-CHP compared with Pola-R-CHP in previously untreated DLBCL: final results from a phase 2 study.

This phase 2 study evaluated mosunetuzumab plus cyclophosphamide, doxorubicin, prednisone, and polatuzumab vedotin (Pola-M-CHP) vs Pola-rituximab (R)-CHP for first-line treatment of diffuse large B-cell lymphoma. Patients were randomized 2:1 to receive 6 cycles of Pola-M-CHP or Pola-R-CHP on day 1 of each 21-day cycle. Mosunetuzumab was administered intravenously via step-up dosing during cycle 1 and at 30 mg on day 1 of subsequent cycles.

Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomas.

Mosunetuzumab and other CD20/CD3 bispecific antibodies (BsAbs) have efficacy in B-cell lymphomas relapsing after or refractory to CD19-directed chimeric antigen receptor (CAR)-modified T cells (CAR-T). The optimal timing of BsAbs and biomarkers of BsAb response after CAR-T are unknown. We addressed these questions using clinical data and blood samples from patients previously treated with CAR-T and subsequently treated on a phase 1/2 study of mosunetuzumab.

A Novel Step-Up Dosage Regimen for Enhancing the Benefit-to-Risk Ratio of Mosunetuzumab in Relapsed or Refractory Follicular Lymphoma.

Mosunetuzumab, a T-cell engaging bispecific antibody targeting CD20xCD3, is approved for treating relapsed/refractory follicular lymphoma. This research supports the approved intravenous clinical dose regimen, summarizing the exposure-response relationships for clinical safety and efficacy. A population pharmacokinetic model and E logistic regression exposure-response models for safety and efficacy were developed using data from 439 patients with relapsed/refractory non-Hodgkin lymphoma and 159 patients with relapsed/refractory follicular lymphoma, respectively, from a Phase I/II study (NCT02500407).

Automated Lugano Metabolic Response Assessment in F-Fluorodeoxyglucose-Avid Non-Hodgkin Lymphoma With Deep Learning on F-Fluorodeoxyglucose-Positron Emission Tomography.

Purpose: Artificial intelligence can reduce the time used by physicians on radiological assessments. For F-fluorodeoxyglucose-avid lymphomas, obtaining complete metabolic response (CMR) by end of treatment is prognostic.

Methods: Here, we present a deep learning-based algorithm for fully automated treatment response assessments according to the Lugano 2014 classification.

Population pharmacokinetics and CD20 binding dynamics for mosunetuzumab in relapsed/refractory B-cell non-Hodgkin lymphoma.

Mosunetuzumab (Mosun) is a CD20xCD3 T-cell engaging bispecific antibody that redirects T cells to eliminate malignant B cells. The approved step-up dose regimen of 1/2/60/30 mg IV is designed to mitigate cytokine release syndrome (CRS) and maximize efficacy in early cycles. A population pharmacokinetic (popPK) model was developed from 439 patients with relapsed/refractory B-Cell Non-Hodgkin lymphoma receiving Mosun IV monotherapy, including fixed dosing (0.

Durable Responses With Mosunetuzumab in Relapsed/Refractory Indolent and Aggressive B-Cell Non-Hodgkin Lymphomas: Extended Follow-Up of a Phase I/II Study.

JCO Mosunetuzumab is a CD20xCD3 T-cell-engaging bispecific antibody administered as an off-the-shelf, fixed-duration treatment in an outpatient setting. We report an updated analysis of the durability of response, by investigator assessment, after an overall median follow-up of 3.5 years in patients with relapsed/refractory indolent or aggressive B-cell non-Hodgkin lymphoma (iNHL/aNHL) from the dose-escalation stage of a phase I/II study of mosunetuzumab (ClinicalTrials.

Loss of CD20 expression as a mechanism of resistance to mosunetuzumab in relapsed/refractory B-cell lymphomas.

CD20 is an established therapeutic target in B-cell malignancies. The CD20 × CD3 bispecific antibody mosunetuzumab has significant efficacy in B-cell non-Hodgkin lymphomas (NHLs). Because target antigen loss is a recognized mechanism of resistance, we evaluated CD20 expression relative to clinical response in patients with relapsed and/or refractory NHL in the phase 1/2 GO29781 trial investigating mosunetuzumab monotherapy.

Matching-adjusted indirect comparison from the Lymphoma Epidemiology of Outcomes Consortium for Real World Evidence (LEO CReWE) study to a clinical trial of mosunetuzumab in relapsed or refractory follicular lymphoma.

Mosunetuzumab is a novel bispecific antibody targeting epitopes on CD3 on T cells and CD20 on B cells with the goal of inducing T-cell mediated elimination of malignant B cells. A recent pivotal phase I/II clinical trial (GO29781) demonstrated that mosunetuzumab induced an overall response rate (ORR) of 80%, complete response (CR) rate of 60%, and a median progression-free survival (PFS) of 17.9 months in patients with relapsed/refractory (R/R) follicular lymphoma (FL) following at least two prior lines of systemic therapy, including alkylator and anti-CD20 antibody-based therapy.

Indirect Treatment Comparisons of Mosunetuzumab With Third- and Later-Line Treatments for Relapsed/Refractory Follicular Lymphoma.

Background: No established standard of care exists for relapsed/refractory (RR) follicular lymphoma (FL) after ≥2 prior therapies. We conducted indirect treatment comparisons (ITCs) to compare the efficacy and tolerability of mosunetuzumab with those of available treatments used in this setting.

Methods: A systematic literature review (SLR) and subsequent feasibility assessments were conducted to identify the most suitable comparator studies in terms of design, available endpoints and populations.

Comparative effectiveness between mosunetuzumab monotherapy clinical trial and real-world data in relapsed/refractory follicular lymphoma in third or subsequent lines of systemic therapy.

A comparison of clinical outcomes in the third or subsequent line (3 L+) of systemic therapy between a real-world data (RWD) external control cohort and a mosunetuzumab single-arm clinical trial cohort is presented. Data for 3 L + patients with relapsed/refractory follicular lymphoma (FL) were obtained from the mosunetuzumab single-arm trial ( = 90) and a US electronic health records database ( = 158), with patients meeting key eligibility criteria from the trial, balanced on pre-specified prognostic factors. Overall response and complete response rates were 80% and 60% in the mosunetuzumab cohort and 75% and 33% in the RWD cohort, odds ratios of 1.

Mosunetuzumab in combination with CHOP in previously untreated DLBCL: safety and efficacy results from a phase 2 study.

Up to 40% of patients with diffuse large B-cell lymphoma (DLBCL) are refractory to or relapse after first-line therapy, highlighting the need for better treatments. Mosunetuzumab is a CD20 × CD3 bispecific antibody that engages and redirects T cells to eliminate malignant B cells. In this phase 2, open-label study (NCT03677141), 40 patients (52.

Intraoperative Ultrasound and Findings of Lumbar Intradural Disk Herniation Causing Cauda Equina Syndrome.

Intradural lumbar disk herniation (ILDH) is a rare variant and accounts for 0.33%-1.5% of lumbar disk herniations.

Mosunetuzumab monotherapy is active and tolerable in patients with relapsed/refractory diffuse large B-cell lymphoma.

As part of a phase 1 or 2 study, this single-arm expansion cohort established the efficacy and safety of mosunetuzumab monotherapy in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) (received ≥2 previous lines of therapy). Intravenous mosunetuzumab was administered with cycle (C) 1 step-up dosing for cytokine release syndrome (CRS) mitigation: C1 day (D) 1: 1 mg; C1D8 2 mg; C1D15 and C2D1: 60 mg; C3 + D1: 30 mg. Hospitalization was not mandatory.

Systems-based digital twins to help characterize clinical dose-response and propose predictive biomarkers in a Phase I study of bispecific antibody, mosunetuzumab, in NHL.

Phase I oncology clinical trials often comprise a limited number of patients representing different disease subtypes who are divided into cohorts receiving treatment(s) at different dosing levels and schedules. Here, we leverage a previously developed quantitative systems pharmacology model of the anti-CD20/CD3 T-cell engaging bispecific antibody, mosunetuzumab, to account for different dosing regimens and patient heterogeneity in the phase I study to inform clinical dose/exposure-response relationships and to identify biological determinants of clinical response. We developed a novel workflow to generate digital twins for each patient, which together form a virtual population (VPOP) that represented variability in biological, pharmacological, and tumor-related parameters from the phase I trial.

Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study.

Background: Mosunetuzumab is a CD20 × CD3 T-cell-engaging bispecific monoclonal antibody that redirects T cells to eliminate malignant B cells. In a phase 1 study, mosunetuzumab was well tolerated and active in patients with relapsed or refractory B-cell lymphoma. We, therefore, aimed to evaluate the safety and anti-tumour activity of fixed-duration mosunetuzumab in patients with relapsed or refractory follicular lymphoma who had received two or more previous therapies.

Treatment patterns and outcomes of patients with relapsed or refractory follicular lymphoma receiving three or more lines of systemic therapy (LEO CReWE): a multicentre cohort study.

Background: Novel therapies for relapsed or refractory follicular lymphoma are commonly evaluated in single-arm studies without formal comparison with other treatments or historical controls. Consequently, rigorously defined treatment outcomes informing expectations for novel therapeutic strategies in this population are sparse. To inform outcome expectations, we aimed to describe treatment patterns, survival outcomes, and duration of response in patients with relapsed or refractory follicular lymphoma receiving three or more lines of systemic therapy.

Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients With Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study.

Purpose: Mosunetuzumab is a bispecific antibody targeting CD20 and CD3 that redirects T cells to engage and eliminate malignant B cells and is being developed for relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs).

Methods: This first-in-human trial (ClinicalTrials.gov identifier: NCT02500407) evaluated the safety and tolerability and efficacy of mosunetuzumab in patients with R/R B-NHL and established the recommended phase II dose.

Phase I Basket Study of Taselisib, an Isoform-Selective PI3K Inhibitor, in Patients with -Mutant Cancers.

Purpose: Somatic mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (), which encodes the p110α catalytic subunit of PI3K, are found in multiple human cancers. While recurrent mutations in helical, regulatory, and kinase domains lead to constitutive PI3K pathway activation, other mutations remain uncharacterized. To further evaluate their clinical actionability, we designed a basket study for patients with -mutant cancers with the isoform-specific PI3K inhibitor taselisib.