Novel Combo Therapy Shows Promise in Certain Patients With Non-Hodgkin Lymphoma

Patients with aggressive relapsed or refractory B-cell non-Hodgkin lymphoma achieved significant responses to treatment with mosunetuzumab plus Polivy (polatuzumab vedotin), according to study results.

The findings, which were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, also demonstrated that the combination was safe in this patient population.

Previously, data have shown that treatment with mosunetuzumab alone was safe and effective in treating relapsed/refractory non-Hodgkin lymphoma (NHL).

Additionally, recent results from a mouse model indicated that combining mosunetuzumab with Polivy conferred increased efficacy compared to either agent alone.

“These data supported a phase 1b/2 open-label multicenter trial of M-Pola for relapsed-refractory B-NHL,” lead study author Dr. Elizabeth Budde, of City of Hope, said during a presentation of the study results.

Here, Budde presented early clinical data from the dose-finding phase 1b cohort comprised of 22 patients (median age, 70 years; 50% men) with either relapsed/refractory follicular lymphoma (FL) or aggressive NHL, including diffuse large B-cell lymphoma (12 patients), transformed FL (4 patients) and FL grade 3b (3 patients).

Patients were excluded from enrollment onto trial if they had received CD20-directed bispecific antibodies, as well as immunochemotherapy within four weeks of the first dose of study drug or radiotherapy within two weeks of first dose of study drug.

Determining a recommended phase 2 dose of study drug served as this cohort’s main goal.

Patients had received a median three prior lines of therapy (range, 1-10), and seven patients had previously received treatment with a CAR-T cell therapy.

At a median follow-up of 9.6 months, all patients experienced at least one side effect. Neutropenia (low white blood cell count) and nausea (40.9%, respectively), as well as fatigue and diarrhea (36.4%, respectively) were the most common treatment-related side effects. Two patients experienced a fatal event — one because of sudden cardiac death and another because of respiratory failure. However, the study authors noted that those deaths were not considered related to treatment. Of note, side effects led to dose modification among eight patients and treatment discontinuation in three patients.

Two cases of cytokine release syndrome (release of cytokines into the blood from immune cells affected by treatment) occurred during the course of therapy; however, both were considered non-severe and were treated without the need of the immunosuppressive drug Actemra (tocilizumab), admission to the ICU or use of vasopressors (used to raise low blood pressure).

Importantly, Budde noted, there were no side effects of neurotoxicity.

More than half of the patient population (54.5%) achieved a complete response to treatment.

“(Mosunetuzumab with polatuzumab vedotin) showed promising efficacy in patients with relapsed/refractory NHL with predominantly aggressive histology,” Budde concluded. “Complete response rate was seen in … patients who failed prior CAR Ts and patients with high-grade lymphoma.”

The phase 2 expansion cohort in patients with relapsed/refractory DLBCL is currently ongoing.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here