New immunotherapy shows complete responses in mantle cell lymphoma

Patients with a rare blood cancer that has relapsed or become resistant to treatment have shown a high response rate to a potent new immunotherapy drug, in a Peter Mac-led clinical trial.

The early-phase NP30179 trial involved 60 patients who were treated with glofitamab, a drug which harnesses the patient’s immune system to fight their cancer.

Professor Michael Dickinson said all patients in the trial had uncontrolled MCL despite receiving an average of two previous treatments, and yet “complete responses” were seen for most.

A complete response means the patient’s blood cancer became undetectable, and this was seen in 78% of trial participants. The overall response rate, including patients who had a complete or partial response, was 85%.

“These are impressive results in a group of patients with heavily pre-treated MCL, a cancer that is usually considered incurable,” says Prof Dickinson, who leads the Aggressive Lymphoma stream at Peter Mac.

“The exciting responses we’ve observed suggest a potential shift in practice, however a larger Phase III clinical trial is underway globally and its results are eagerly awaited.”

Results of the completed Phase I / II clinical trial were published Oct. 4 in the Journal of Clinical Oncology.

Notably, positive responses to glofitamab were seen in a subset of MCL patients known to have a particularly poor prognosis—that is MCL patients who relapse after prior treatment with a BTKi (bruton tyrosine kinase inhibitor) drug.

In the trial, MCL patients with prior BTKi treatment showed a complete response rate of 71%, while the overall response rate was 74%. These patients’ responses to chemotherapy—the current standard of care—are expected to be much lower.

In the Phase I / II trial, participants also received pre-treatment with another immunotherapy, obinutuzumab, ahead of glofitamab in the hope this would reduce the risk of Cytokine release syndrome (CRS).

This common immunotherapy side-effect involves the patient’s immune system responding too aggressively. CRS was still seen in 70% of trial participants and Prof Dickinson said this was “manageable with appropriate support.”

MCL is an aggressive, relatively rare type of non-Hodgkin lymphoma. Around 500 Australians will be diagnosed with MCL this year, this cancer accounting for about 5% to 10% of all non-Hodgkin lymphomas.

The ongoing Phase III trial is assessing glofitamab in combination with another drug and is running in collaboration with the Australasian Leukaemia Lymphoma Group.