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Poor Prognosis NHL Patients May Benefit From Mosunetuzumab

The dual-targeted immunotherapy agent mosunetuzumab has induced a durable complete remission in heavily pretreated non-Hodgkin lymphoma patients
10 Dec 2019
Clinical Research;  Immunotherapy;  Lymphomas

Author: By Lynda Williams, Senior medwireNews Reporter 

 

medwireNews: An “off-the-shelf” bispecific antibody has shown promising efficacy in a phase I/Ib trial of patients with recurrent or refractory non-Hodgkin lymphoma (NHL), including some individuals who have previously received chimeric antigen receptor T-cell (CAR-T) therapy. 

The research was presented by Stephen Schuster, from the University of Pennsylvania in Philadelphia, USA, at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida, USA. 

He explained that mosunetuzumab targets a protein on the tumour cell surface and a second protein on the patient’s T cell surface, inducing T-cell targeting of B cells and an increase in tumour infiltrating lymphocytes. 

Mosunetuzumab was delivered intravenously to 270 patients aged a median of 62 years (63.7% male), the majority (66.7%) of whom had aggressive NHL, most commonly diffuse large B-cell lymphoma (DLBCL; 43.3% of the full cohort), while the remaining 31.5% had indolent NHL, most commonly follicular lymphoma (FL; 30.4% of full cohort). 

The group had received a median of three prior systemic treatments, including 30 patients who had been given CAR-T therapy for DLBCL, transformed FL or FL; 96.7% of these 30 patients were refractory to anti-CD20 therapy, 83.3% to their last treatment, and 73.3% to CAR-T therapy.  

The dose-finding study used a step-up dosing schedule on days 1, 8 and 15 of the first 21-day cycle, followed by a fixed dose on each subsequent cycle. Treatment-related adverse events (TRAEs) at grade 3–5 occurred in 34.1% of the cohort, including serious TRAEs in 18.9%. The most common grade 3–4 TRAEs were neutropenia (21.8%), hypophosphatemia (13.3%) and anaemia (8.9%), and there were five fatalities reported, namely Candida sepsis, large intestine perforation, pneumonia, volvulus and sepsis. 

In all, 20.0% of patients experienced a TRAE requiring dose delay or reduction, and 2.6% withdrew because of TRAEs, with 95% of AEs occurring in the first cycle and no evidence for cumulative or chronic toxicity, the presenter commented. 

In the aggressive NHL subgroup, the objective response rate (ORR) was 37.1%. This included a complete response (CR) for 19.4% of the patients, of whom 70.8% have remained in remission for up to 16 months off treatment.  

And ORR and CR rates were similar in the subgroup of 98 aggressive NHL patients who had received at least two lines of treatment for DLBCL/transformed FL, at 37.8% and 20.4%, respectively. This included patients who were refractory to CD20-targeted treatment or had undergone autologous stem cell transplantation. 

For patients with indolent NHL, the ORR was 62.7% and the CR rate 43.3%, with 82.8% of the 24 patients with a CR continuing in remission after up to 26 months off treatment. 

Analysis of the subgroup of 61 patients who had received at least two lines of treatment for FL gave corresponding rates of 63.9% and 44.3%, with similar responses found among those refractory to both CD20 and alkylating agents (65.1 and 44.2%), or with disease progression within 2 years of first treatment (60.6 and 42.4%). The rates rose to 88.9% and 77.8% for the nine individuals who were refractory to PI3KI therapy.

Stephen Schuster concluded that mosunetuzumab “exhibits a promising benefit-risk profile in patients with [recurrent/refractory] B-cell lymphomas”, including achieving CRs in high-risk groups.

“Dose optimization is ongoing”, the presenter added, noting that evidence of a dose–response association would also be presented at the 2019 ASH meeting, and that mosunetuzumab is now being assessed both as a single-agent and in combinations, including in treatment-naïve patients. 

 

Reference  

Schuster SJ, Bartlett NL, Assouline S, et alMosunetuzumab induces complete remissions in poor prognosis non-Hodgkin lymphoma patients, including those who are resistant to or relapsing after chimeric antigen receptor T-Cell (CAR-T) therapies, and is active in treatment through multiple lines. 61st ASH Annual Meeting and Exposition; Orlando, Florida, USA: 7–10 December 2019.  

medwireNews (www.medwireNews.com ) is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

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