Fixed-duration mosunetuzumab therapy demonstrated a 78% overall response rate (ORR) with a 60.0% complete response (CR) rate among patients with follicular lymphoma (FL) who had received at least two prior lines of therapy. The CR rate was consistently high across high-risk disease subgroups, and patients had durable responses with more than three years of follow-up. These subgroup analyses of the pivotal phase II trial in patients with heavily pretreated FL were presented at the European Hematology Association (EHA) 2024 Congress.
“The responses … in patients with FL with at least two prior lines of treatment are high and durable with 30-month median duration of CR not reached after three years of follow-up. Seventy-one percent of patients in CR remain in CR,” study author Elizabeth Budde, MD, PhD, a hematologist-oncologist at City of Hope National Medical Center in Duarte, California, told ASH Clinical News.
“Overall, patients benefit from durable responses without compromising immune function. The patients can maintain remissions despite finite therapy [with mosunetuzumab]. This benefit is compounded by patients’ B-cell and immunoglobulin recovery,” said study author Sarit Assouline, MD, MSc, a hematologist at the Jewish General Hospital of McGill University in Montreal who presented the data at the EHA meeting.
Mosunetuzumab received accelerated approval by the U.S. Food and Drug Administration (FDA) in December 2022 for adult patients with relapsed or refractory (R/R) FL who had received two or more lines of systemic therapy based on the results of a pivotal phase II study. Mosunetuzumab is a humanized bispecific antibody that binds to CD20 on cancer B cells, including FL cells, and CD3 on T cells, directing T-cell cytotoxic activity to the cancerous cells. Mosunetuzumab infusions are given in an outpatient setting without the need for hospitalization.
“Autologous CAR [chimeric antigen receptor]-T therapy and obinotuzumab in combination with zanubrutinib are two other standard-of-care options indicated for these patients,” Dr. Budde said. “However, there is need to provide assistance to overcome logistical challenges so all these good options are available to all patients.”
At the EHA meeting, Dr. Assouline presented updated subanalysis data with a median follow-up of 37.4 months. Ninety patients on the trial received mosunetuzumab monotherapy, given via intravenous infusion, for eight cycles if the patient achieved a CR by cycle eight or for 17 cycles if the patient achieved a maximal response of a partial response (PR) or stable disease by cycle eight.
Patients had a median age of 60, and 61% were male. Thirty patients were 65 years or older. Patients had a median of three prior lines of therapy, 69% were refractory to their prior therapy, and 79% were refractory to a prior anti-CD20 therapy. A total of 47 patients (52%) were so-called POD24, meaning they had progression or relapse of their FL within two years after diagnosis, which is associated with poor outcomes for patients treated with the standard-of-care R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone).
The ORR was 81% among POD24 patients including 59.6% who had a CR. Among non-POD24 patients, the ORR was 74%, and the CR was 60.5%. The highest CR rate was 68.6%, achieved among those patients who had had three prior lines of therapy.
Patients who had four or more prior lines of therapy had an ORR of 73% and a CR of 54.5%.
“Excellent responses and safety are seen across the board regardless of age or POD24 status, which was a well-known poor prognostic factor in the old days,” Dr. Budde noted.
The median duration of response (DOR) was not yet reached. The 30-month DOR in the overall population was 56%. Patients who had had three prior lines of therapy had a 30-month DOR of 77% compared to 66% among those with four or more prior lines of therapy. POD24 patients had a 30-month DOR of 67% compared to 75% among non-POD24 patients.
The 36-month progression-free survival (PFS) rate was 43% in the overall population, and the median PFS was 24.0 months. The median overall survival (OS) has not yet been reached. The 36-month OS rate was 83%. The 36-month PFS rate among POD24 and non-POD24 patients was 44% and 42%, respectively.
“[These data] provide the longest follow-up results for bispecific antibody treatment in lymphoma. The results are consistent with the drug’s mechanism of action,” Dr. Budde added.
The safety profile is consistent with the prior safety data with mosunetuzumab. Only 2% of patients had a discontinuation that was mosunetuzumab related. Overall, 70% of patients experienced a grade 3-4 adverse event, and 51% of events were drug related. Twenty-nine percent of patients experienced neutropenia, and 20% had a serious infection. Forty-four percent of patients had cytokine release syndrome (CRS); however, only 1% had grade 3 and 1% had grade 4 CRS.
“Mosunetuzumab use in R/R FL has the lowest CRS rate among all anti-CD20/CD3 bispecific antibodies,” Dr. Budde said. “Strikingly, the CRS rate, neutropenia incidence, and serious infection rates are numerically lower in patients 65 years old or older. These patients represented a third of the patients on the pivotal trial with the oldest one at 90 years old. The favorable safety profile supports the use of mosunetuzumab to all adult patients regardless of age.
“Additionally, the very low serious infection events (only three on the trial) beyond cycle eight are a strong endorsement of the long-term safety of fixed-duration treatment. This is also supported by the nice recovery of B cells and immunoglobulins after the completion of treatment,” Dr. Budde said.
According to Dr. Budde, mosunetuzumab is an effective treatment option for patients with R/R FL. It has the advantage of being an off-the-shelf, fixed-duration treatment. CAR T-cell therapy is also a good option for those who have access to a CAR-T treatment center and no logistical issues, and desire a one-time treatment, she added. “The recent approval of obinotuzumab and zanubritinub provides another option for those who do not have access to CAR T or bispecific treatment. We are in an exciting era with several novel treatments available for patients with FL with multiple prior lines of therapy. Four years ago, none of these was available outside of clinical trials.”
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Assouline S, Bartlett NL, Matasar M, et al. Mosunetuzumab demonstrates clinically meaningful outcomes in high-risk patients with heavily pre-treated R/R FL after ≥3 years of follow-up: subgroup analysis of a pivotal phase II study. Abstract S233. Presented at the European Hematology Association 2024 Congress; June 14, 2024; Madrid, Spain.
