Mosunetuzumab

Mosunetuzumab is a bispecific antibody that targets both CD3 which is on the surface of T cells and CD20, on the surface of B cells.

Mosunetuzumab, sold under the brand name Lunsumio, is a monoclonal antibody used for the treatment of follicular lymphoma.

It bispecifically binds CD20 and CD3 to engage T-cells.

It targets CD 20, a protein found almost lymphoma cells.

The CD3 proteins is present on immune T cells: it redirects the immune T cells to recognize lymphoma cells to kill them via a CD2 dependent pathway.

It is both a targeted and immunotherapy.

The most common adverse reactions (≥20%) include cytokine release syndrome, fatigue, rash, pyrexia, and headache.

The most common grade 3 to 4 laboratory abnormalities (≥10%) include decreased lymphocyte count, decreased phosphate, increased glucose, decreased neutrophil count, increased uric acid, decreased white blood cell count, decreased hemoglobin, and decreased platelets.

Mosunetuzumab is indicated for the treatment of adults with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.

It works by redirecting T cells to engage and eliminate malignant B cells.

Monoclonal antibody engages T cells and directs their cytotoxicity against B cells.

The antibody uses the patient’s own T cells to do what a CAR T cell would do.

Unlike CAR T cells, which are prepared for each individual patient in a complex process that involves genetic engineering that can take several weeks, mosunetuzumab can be given to patients immediately by intravenous infusion.

In a phase 1/1b trial (known as GO29781) conducted in 270 patients with poor-prognosis refractory/relapsed non-Hodgkin’s lymphoma: These patients had no available therapy that would be expected to improve survival

Objective responses were seen in 46 of 124 patients (37%) with aggressive lymphomas, and 24 (19%) of these patients achieved a CR.

Among patients with indolent lymphoma, objective responses were seen in 42 of 67 patients (63%) and 29 of 67 (43%) had CR.

Complete remissions appear to be long-lasting.

17 of 24 patients (71%) with aggressive lymphoma and 24 of 29 patients (83%) with indolent lymphomas remained free of disease.

These rates are similar to what was seen in patients with aggressive lymphoma who had not previously received CAR T-cell therapy.

It may also help augment the effect of the prior CAR-T treatment.

Re-treatment with mosunetuzumab in patients who achieved CR and stopped treatment and relapsed, they were re-treated, and the responses seen on this retreatment were similar to those seen with initial treatment.

Adverse events are similar to those seen with CAR T cells: namely cytokine release syndrome, which was mostly mild and seen in 29% of patients; and neurological toxicity, which was moderately severe in 4% patients.

Can cause fever, and temporary low blood counts.

May be associated with lowering of immunoglobulins due to the depletion of normal B cells.

The results show that mosunetuzumab generates long-lasting responses with a very tolerable safety profile in patients with B-cell non-Hodgkin lymphomas for whom multiple prior treatments have failed and whose prognosis is poor.

Durable complete remissions in patients whose lymphomas progressed after CAR T therapy.

Toxicity seen with the drug are less than has been seen with CAR T cells, and the risk of high-grade CRS and neurological toxicity is very low.

It stimulates and invigorates T cells, and could be useful as a pre-treatment or a bridge to CAR T-cell therapy, .

Could be used before CAR T-cell therapy, and equally it could be used after CAR T cell therapy, as it could boost responses in both cases.

It has a boxed warning for serious or life-threatening cytokine release syndrome.