June 27, 2023

Kristi Rosa

Fixed-duration treatment with single-agent mosunetuzumab resulted in a high complete response rate by end of treatment in patients with relapsed or refractory follicular lymphoma, according to updated data from the phase 2 GO29781 trial.

Fixed-duration treatment with single-agent mosunetuzumab (Lunsumio) resulted in a high complete response (CR) rate by end of treatment (EOT) in patients with relapsed or refractory follicular lymphoma, according to updated data from the phase 2 GO29781 trial (NCT02500407) presented at the 17th International Conference on Malignant Lymphoma.

At a median follow-up of 28.3 months, the median duration of CR in the patients who achieved a CR by EOT (n = 49) was not yet estimable (NE; 95% CI, 23.2-NE). The 24-month duration of CR rate was 65% (95% CI, 39%-90.5%). Moreover, the median progression-free survival (PFS) was also NE (95% CI, 26.3-NE), and the 24-month PFS rate after the first dose of mosunetuzumab was 77% (95% CI, 63.3%-91.0%). The median overall survival (OS) was also NE (95% CI, NE-NE) and the 24-month OS rate was 100% (95% CI, 100%-100%).

“In this pivotal phase 2 study, fixed-duration mosunetuzumab demonstrated a high CR rate at EOT in patients with relapsed or refractory follicular lymphoma,” Laurie H. Sehn, MD, MPH, lead study author and clinical professor with the BC Cancer Centre for Lymphoid Cancer and University of British Columbia in Vancouver, Canada, said in a presentation of the data. “Durable responses were observed in these patients, with a high proportion of patients remaining event free at 2 years despite the fixed duration of treatment.”

It is known the follicular lymphoma represents the most common indolent subtype of non-Hodgkin lymphoma, with most patients experiencing relapse. These patients are at higher risk of transformation to aggressive lymphoma, which is known to have poor outcomes, according to Sehn. The first-in-class CD20xCD3 T-cell–engaging bispecific antibody, mosunetuzumab, is designed to redirect T cells to engage and kill malignant B cells. The agent has emerged as a potential therapeutic option for this population.

The phase 2 trial enrolled patients with relapsed or refractory follicular lymphoma who had grade 1 to 3a disease and who had previously received at least 2 therapies, which included an anti-CD20 antibody and an alkylating agent. Patients were required to have an ECOG performance status of 0 or 1.

Study participants were administered mosunetuzumab intravenously in 21-day cycles with step-up dosing in cycle 1 “to mitigate cytokine release syndrome [CRS],” Sehn explained. Post-infusion hospitalization for monitoring was not required. In the first treatment cycle, the agent was given at 1 mg on day 1, 2 mg on day 8, and 60 mg on day 15. For day 1 of cycles 2 and 3, the agent was administered at 60 mg and 30 mg, respectively.

“In this fixed-duration schedule, patients initially received 8 cycles of therapy,” Sehn added. “If they were in complete response [CR] after 8 cycles, they received no further treatment. But if they were in a partial response or stable disease, they could receive up to 17 cycles.”

CR rate by independent review committee assessment and Cheson 2007 criteria served as the primary end point. Investigators also evaluated safety, particularly CRS, by utilizing American Society for Transplantation and Cellular Therapy criteria. They conducted exploratory analyses that evaluated the link between baseline total metabolic tumor volume (TMTV) and safety and efficacy of the agent, and this was measured using an artificial intelligence–based model.

Previous data from the trial showed that the CR rate with mosunetuzumab was 50% and the objective response rate was 80%. Moreover, the 24-month median duration of CR rate was 63%.

With the updated analysis, the median time on study for patients was 28.3 months (range, 2-38), and 81% of patients remained in follow-up. More than half of patients (62%) completed initial study treatment, and 38% discontinued. Twenty-seven percent of patients discontinued because of disease progression (PD). Notably, most patients (82%) received up to 8 cycles of treatment, Sehn said.

As of the cutoff date of July 8, 2022, data continued to showcase clinically meaningful outcomes with mosunetuzumab. Sixty percent of patients achieved a CR at EOT; of these 54 patients, 49 achieved a CR at EOT, 1 patient who had a CR experienced PD in cycle 8, and 4 patients had a CR following EOT because of delayed bone marrow confirmation.

When comparing baseline characteristics between those who achieved a CR at EOT (n = 49) vs those who did not (n = 41), Sehn noted that the median age (63 years vs 59 years), Ann Arbor disease stage (I/II, 18% vs 29%; III/IV, 82% vs 71%), and ECOG performance status (0, 61% vs 56%; 1, 39% vs 44%) were comparable. Both groups had received a median of 3 prior lines of therapy (range, 2-10).

“In those patients who had achieved a CR at EOT, 71% of them had been refractory to prior anti-CD20 therapy and 52% were POD24,” she added. “In the patients who didn’t achieve a CR at EOT, they were slightly more likely to be refractory to their last line of therapy and to be double refractory.”

Additional data showed that of the 54 patients who achieved CR as best response, 33 had achieved their CR at the time of the first response assessment at 3 months and 21 patients had their CR after the first response assessment; these patients were categorized in early CR and late CR groups, respectively. The median DOR was not yet reached in either group. “There was no correlation between DOR, PFS, or OS according to timing of achieving CR,” Sehn noted.

Sixteen patients achieved a partial response only as their best response and the median DOR in this group was 4.0 months (95% CI, 2.5-6.7).

Eighty-two patients had a TMTV measurement at baseline and no correlation was found between baseline TMTV and best overall response. “Importantly, many patients achieving a CR had a high TMTV at baseline,” Sehn said.

Regarding safety, any-grade CRS was reported in 44% of patients; this was grade 1 in 26% of patients, grade 2 in 17% of patients, grade 3 in 1% of patients, and grade 4 in 1% of patients. The median time to onset in day 1 of cycle 1 was 5.2 hours (range, 1.2-24) and 27 hours (range, 0.1-391) in day 15 of cycle 1. The median duration of CRS was 3 days (range, 1-29). Eleven percent of patients received corticosteroids, and 8% were given tocilizumab (Actemra).

“There were no new events of CRS since the previous report and all events of CRS resolved,” Sehn said.

In an exploratory analysis, investigators sought to determine which patients may have a higher likelihood of having grade 2 or higher CRS. “One of the interesting things that stood was that it seemed to be of higher likelihood in patients who had disease burden in the bone or bone marrow at the time of initiation,” Sehn concluded.

Editor’s Note: Dr Sehn disclosed that she received consulting/honoraria from Amgen, AbbVie, AstraZeneca, Bristol Myers Squibb/Celgene, Gilead Sciences, Janssen-Ortho, Kite, Merck, F. Hoffman-La Roche Ltd./Genentech, Inc., Seagen, Takeda, Teva, TG Therapeutics, Incyte, Sandoz-Novartis, Nurix, and Genmab. Research funding was provided by F. Hoffman-La Roche Ltd./Genentech, Inc., and Teva.

Reference

Sehn LH, Bartlett NL, Matasar M, et al. Mosunetuzumab demonstrates durable responses in patients with relapsed/refractory follicular lymphoma and ≥2 prior therapies: updated analysis of a pivotal phase II study. Hematol Oncol. 2023;41(suppl 2):122-125. doi:10.1002/hon.3163_83