High objective response and complete response rates observed with mosunetuzumab in patients with relapsed/refractory follicular lymphoma.
Mosunetuzumab (Lunsumio) induces high complete remission rates and a tolerable safety profile when used as treatment in patients with relapsed/refractory follicular lymphoma (FL) who had previously received 2 or more lines of therapy, including an anti-CD20 and an alkylating agent, according to findings from the phase 1/2 study GO29781(NCT02500407) reported in the Lancet Oncology.1
At the median follow-up of 18.3 months (range, 13.8-23.3), 54 of the 90 enrolled patients (60%) had a complete response (CR; 95% CI, 49.1%-70.2%), meeting one of the trial’s primary end points. This observed response rate was significantly higher than the historic control copanlisib (Aliqopa; 14%; P <.0001).
“In this study, fixed-duration mosunetuzumab induced a high proportion of objective responses and complete responses in a heavily pretreated population of patients with relapsed or refractory follicular lymphoma. The study met its primary efficacy endpoint, with a complete response rate of 60.0%,” wrote the study investigators. “Response rates were generally consistent across patient subgroups with risk factors for poor prognosis, although the small patient numbers in some of these subgroups should be noted. Responses occurred early in the treatment course and were durable.”
The open-label, multicenter, phase 1/2 trial was conducted at 49 institutions across 7 countries to examine the safety and antitumor activity of fixed-duration mosunetuzumab in patients with relapsed or refractory FL who had received 2 or more prior therapies.2
Enrollment was open to patients aged 18 years or older with histologically confirmed disease, an ECOG performance status of 0-1, and adequate hepatic, hematologic, and renal function. Those enrolled were treated with mosunetuzumab administered intravenously in 21-day cycles with cycle 1 step-up dosing consisting of 1 mg on day 1, 2 mg on day 8, 60 mg on cycle 1 day 15 and cycle 2 day 1, and 30 mg on day 1 of cycle 3 and onwards.
The primary end point included the CR rate assessed by independent review committee (IRC). Secondary end points were duration of response (DOR), progression-free survival (PFS), overall survival, European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30), and investigator assessed CR and objective response rate (ORR).
Between May 2, 2019, and September 25, 2020, 90 patients were enrolled with the majority of patients men (61%), White (82%), and had stage III or IV disease (77%). Sixty-nine percent of patients were refractory to their last therapy, the median number of prior lines of therapy was 3 (range, 2-4), 59% had an ECOG performance status of 0, and before the study entry, all patients received anti-CD20 therapies and alkylating agents. Additionally, 71 patients (79%) were refractory to any previous anti-CD20 therapy, 48 (53%) were double refractory to both previous anti-CD20 therapy and a previous alkylating agent, and 47 (52%) had a history of progression of disease within 24 months from the start of initial therapy.
At the median follow-up, patients were treated with a median of 8 cycles of mosunetuzumab and 60% completed initial treatment. Discontinuation of treatment occurred in 36 patients due to progressive disease (28%), adverse effects (AEs; 4%), physician’s choice (4%), use of a different anti-lymphoma therapy (2%), and patient withdrawal (1%). By the time of the data cutoff, 2% of patients were on retreatment, 84% were in follow-up, and 13% had discontinued the therapy.
Reduction in tumor size was observed in nearly all patients (94%) and 80.0% (95% CI, 70.3%-87.7%) of patients achieved an objective response. Each of the CRs were confirmed by PET and bone marrow examination.
The median PFS was 17.9 months (95% CI, 10.1–not reached [NR]) with the 12- and 18-month PFS rates at 57.7% (95% CI, 46.9%-68.4%) and 47.0% (95% CI, 34.4%-59.6%) by IRC. By investigator assessment, these PFS rates were 57.6% (95% CI, 46.8%-68.4%) and 51.0% (95% CI, 38.9%-63.0%), respectively.
Median duration of response by IRC was 22.8 months. It was estimated that 56.9% of all responders and 70.2% of all complete responders maintained their responses for 18 months or more. The median duration of CR was NR (95% CI, 14.6-NR) as well as both the median OS and time to next treatment. Further, at 18 months, the event-free survival was 61.0% (95% CI, 50.0%-72.0%) and OS rate was 89.6% (95% CI, 82.5%-96.6%).
In terms of safety, the most frequently observed AEs were cytokine release syndrome (44%), fatigue (37%), and headache (31%). Grade 3/4 AEs consisted of neutropenia or decreased neutrophil count (27%), hypophosphatemia (17%), hyperglycemia (8%), and anemia (8%). Serious AEs were experienced in 47% of patients and 1 patient experienced a grade 5 AE, malignant neoplasm progression of FL.
There were 4 (4%) patients who withdrew from the study due to AEs, including grade 2 cytokine release syndrome, grade 4 cytokine release syndrome, both of which were considered related to mosunetuzumab. The other 2 discontinuations were due to grade 2 Hodgkin lymphoma and grade 4 Epstein-Barr viraemia, both of which were not related to the study. Rates of AEs were similar in patients aged 65 years or younger, over 65 years, and older than 70 years.
Previously, the FDA has granted priority review to an approval application for mosunetuzumab for the treatment of patients with relapsed or refractory FL on July 8, 2022.
“In the current study, mosunetuzumab had a manageable safety profile that was consistent with the phase 1 results and was similar in older and younger patients. Notably, adverse events leading to mosunetuzumab discontinuation were rare and occurred in only four patients. In the pivotal studies of the PI3K inhibitors, adverse events leading to discontinuation occurred in 15%-35% of patients,” wrote the study investigators.