Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive:

Mosunetuzumab, a Dual-Targeted Antibody, Shows Complete Remissions in Relapsed/Refractory NHL After CAR T-Cell Therapy

JHOP - February 2020 Vol 10, No 1 - ASH Highlights, CAR T-Cell Therapy, Lymphoma
Download pdf

Mosunetuzumab is an investigational bispecific T-cell engager (BiTE) agent dually targeting 2 proteins on the surface of lymphoma cells—CD3 (on the surface of T-cells) and CD20 (on the surface of B-cells).

New data presented at ASH 2019 show that mosunetuzumab holds promise as a durable and safe treatment for patients with treatment-refractory non-Hodgkin lymphoma (NHL), including those whose disease progressed after receiving chimeric antigen receptor (CAR) T-cell therapy. In a phase 1/1b clinical trial, the novel BiTE mosunetuzumab achieved durable responses in patients with refractory NHL, including complete remissions in 22.2% of patients who had previously received CAR T-cell therapy.

Lead investigator Stephen J. Schuster, MD, Director, Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, discussed the results.

“CAR-T was the first therapy in about 20 years to make a dent in the treatment of B-cell lymphoma in patients who fail other treatments. About one-third of patients treated with CAR-T have sustained remissions after 5 years, but we need treatments for the other two-thirds who fail. Nothing thus far has been reliable, and the vast majority of patients die within months,” said Dr Schuster.

“Unlike CAR T-cell therapy, mosunetuzumab is an off-the-shelf immunotherapy product that can be given to patients without having to genetically modify their T-cells,” Dr Schuster added.

Dr Schuster envisions mosunetuz­umab as a bridge to CAR T-cell therapy or a rescue therapy for patients who do not respond to CAR T-cell therapy. Mosune­tuzumab is a humanized antibody that binds to CD20 on the surface of malignant B-cells and to CD3 on ­cytotoxic T-cells.

“In binding to the T-cells, it’s [mosunetuzumab] capable of inducing T-cell activation, and, when engaged with a B-cell, it will cause a death of the target cell and eliminate those cells,” Dr Schuster explained.

Study Details

Dr Schuster reported efficacy results for 191 evaluable patients who received treatment with mosune­tuzumab monotherapy during the ongoing phase 1/1b dose-escalation GO29781 study in patients with relapsed or refractory B-cell NHL who had received several lines of therapy.

He focused on the patients in Group B who received mosunetuzumab intravenously, with stepped-up dosing on days 1, 8, and 15 of cycle 1, and then as a fixed dose on day 1 of each subsequent 21-day cycle (maximum, 17 cycles).

Among the 124 patients with aggressive NHL, 46 (37.1%) patients had objective response, including 24 (19.4%) who had a complete remission, according to pooled data from participants who received mosune­tuzumab at doses ranging from 2.8 mg to 40.5 mg. After a median follow-up of 6 months, 17 patients remain in complete remission.

In the 67 patients with indolent NHL, the objective response rate was 62.7% (N = 42), including 29 (43.3%) who had complete remission; the dosing in these cohorts ranged from 2.8 mg to 13.5 mg. A total of 24 patients remain in complete remission up to 26 months after initial treatment.

In addition, mosunetuzumab resulted in responses in patients who had previously received CAR T-cell therapy. Among 18 evaluable patients in this cohort, 7 (38.9%) had an objective response, including 4 (22.2%) with complete remission. The investigators also observed an expansion of lymphocytes, including residual CAR T-cells in 2 of 8 patients, and complete remissions with and without CAR T-cell expansions.

In an interview, Dr Schuster pointed out that these were very sick patients, “who progressed after third-line therapy and would have a dire prognosis. We desperately need solutions for patients who fail CAR-T,” he emphasized.

The evaluable safety population included 270 patients—66.7% of patients with aggressive NHL, mainly diffuse large B-cell lymphoma, and 31.5% with follicular lymphoma and other types of indolent NHL. The patients received a median of 3 previous systemic therapies (range, 1-14). In addition, 28.5% of patients had received autologous stem-cell transplantation, and 71.9% had disease refractory to the last previous therapy.

Of 30 patients who had received CAR T-cell therapy, 22 (73.3%) had refractory disease, with a median of 5 previous systemic treatments.

Mosunetuzumab Safety

Mosunetuzumab had a tolerable safety profile, with mostly low-grade cytokine release syndrome (28% of all grades) and neurologic adverse events (43.7% of all grades), including headache, insomnia, and dizziness.

Overall, 3 (1.1%) cases of grade 3 cytokine release syndrome were reported in the total population (N = 218) and 1 (3.3%) in the previous CAR cohort. The incidence of grade 3 neurologic adverse events was 3.7% in the broad population and 10.0% in the CAR group.

“The safety with regard to cytokine release syndrome and neurological adverse events is almost identical, whether the patients have had prior CAR T-cell therapy or not,” Dr Schuster noted. “What’s interesting is that these events are much more frequent during CAR T-cell therapy.”

Ongoing studies are evaluating mosunetuzumab as monotherapy and in combination with checkpoint inhibitors, in patients with different types of NHL.

Related Items
Kymriah Received Accelerated FDA Approval for Relapsed or Refractory Follicular Lymphoma
JHOP - June 2022 Vol 12, No 3 published on June 16, 2022 in FDA Oncology Update, Lymphoma, CAR T-Cell Therapy
Yescarta First CAR T-Cell Therapy FDA Approved for Large B-Cell Lymphoma
JHOP - June 2022 Vol 12, No 3 published on June 16, 2022 in FDA Oncology Update, CAR T-Cell Therapy, Lymphoma
Carvykti Second BCMA-Directed CAR T-Cell Therapy FDA Approved for Multiple Myeloma
JHOP - April 2022 Vol 12, No 2 published on May 3, 2022 in FDA Oncology Update, CAR T-Cell Therapy, Multiple Myeloma
Hepatitis B Virus Infection Monitoring in Patients with Lymphoma Receiving Anti-CD20 Monoclonal Antibodies
Christopher Sinoimeri, PharmD, Bryan Do, PharmD, BCOP, Sheree Chen, PharmD, BCOP
JHOP - April 2022 Vol 12, No 2 published on May 3, 2022 in Original Article, Lymphoma, Immunotherapy, Infections
Second-Line Axicabtagene Ciloleucel Therapy Improves Outcomes in Patients with Large B-Cell Lymphoma: ZUMA-7
Robert J. Ignoffo, PharmD, FASHP, FCSHP, FHOPA
JHOP - April 2022 Vol 12, No 2 published on May 3, 2022 in From the Literature, Lymphoma, CAR T-Cell Therapy
A Pooled Safety Analysis of Loncastuximab Tesirine in Relapsed or Refractory DLBCL in the LOTIS Clinical Trial Program: Incidence, Onset, and Management of Myelosuppression
JHOP - March 2022 Vol 12 Special Feature published on March 22, 2022 in HOPA Abstracts, Lymphoma
A Review of CAR T-Cell Therapies Approved for the Treatment of Relapsed and Refractory B-Cell Lymphomas
Drew A. Wells, PharmD, BCPS, Jenna Summerlin, PharmD, Zachery Halford, PharmD, BCOP, BCPPS
JHOP - February 2022 Vol 12, No 1 published on March 1, 2022 in Review Article, CAR T-Cell Therapy, Lymphoma
Immune Responses to COVID-19 Vaccines Low Among Patients with Hematologic Malignancies, but mRNA Vaccines Induce Strong Antibody Response in AML and MDS
JHOP - February 2022 Vol 12, No 1 published on March 1, 2022 in ASH Highlights
A Paradigm Shift: CAR T-Cell Therapy Beats Standard of Care as Second-Line Treatment for Large B-Cell Lymphoma
JHOP - February 2022 Vol 12, No 1 published on March 1, 2022 in ASH Highlights
Polatuzumab Vedotin plus R-CHP Outperforms R-CHOP as First-Line Therapy in Patients with Diffuse Large B-Cell Lymphoma
JHOP - February 2022 Vol 12, No 1 published on March 1, 2022 in ASH Highlights
Copyright © The Lynx Group, LLC. All rights reserved.