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December 11, 2023
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'Remarkable' study shows potential of chemotherapy-free regimen for follicular lymphoma

Fact checked byMark Leiser
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SAN DIEGO — Subcutaneous time-limited mosunetuzumab exhibited “highly encouraging efficacy” among patients with newly diagnosed high-burden follicular lymphoma, according to researchers.

Perspective from Joshua Brody, MD

Nearly all patients responded and three-quarters achieved complete response, findings presented at ASH Annual Meeting and Exposition showed.

Graphic showing complete response rate
Data derived from Falchi L, et al. Abstract 604. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2023; San Diego.

“We need longer follow-up to assess durability of responses and to solidify the safety profile analyses,” Lorenzo Falchi, MD, a lymphoma specialist in the department of medicine at Memorial Sloan Kettering Cancer Center, said during a presentation. “But we do think our data support further exploration of frontline mosunetuzumab for patients with follicular lymphoma.”

Traditional chemotherapy with anti-CD20 antibodies has been standard first-line therapy for high-burden follicular lymphoma for at least 2 decades. However, this regimen is not curative for most patients, and it also can result in severe complications.

Because a dysfunctional T-cell infiltrate is a defining factor of follicular lymphoma pathobiology, redirecting T cells to exert anti-tumor activity could represent an effective treatment approach, Falchi said.

Mosunetuzumab (Lunsumio, Genentech) is a humanized bispecific CD20/CD3 antibody that can be administered via IV or subcutaneously.

A previous study showed strong activity of time-limited mosunetuzumab among patients with relapsed/refractory follicular lymphoma, with an 80% overall response rate and 60% complete response rate. Based on those results, the FDA approved the agent in 2022 for treatment of adults with relapsed or refractory follicular lymphoma who received at least two prior systemic therapies.

Falchi and colleagues hypothesized that chemotherapy-naive T cells might exert greater antitumor effects when engaged by mosunetuzumab. They conducted a multicenter phase 2 study to evaluate the agent as fixed-duration first-line therapy for patients with high tumor burden follicular lymphoma.

Researchers enrolled 54 adults (median age, 58 years; range, 26-83; 40.7% women; 79.6% white) with stage II to stage IV disease and ECOG performance status of 0 to 2 who were fit for chemoimmunotherapy and in need of therapy per Groupe d'Etude des Lymphomes Folliculaires criteria.

Most study participants had stage IV disease (72.2%) and ECOG status of 0 (81.5%).

Patients received subcutaneous mosunetuzumab dosed at 5 mg on day 1 and 45 mg on days 8 and 15 of cycle one, followed by 45 on day 1 of each subsequent 21-day cycle.

Premedication included dexamethasone, diphenhydramine and acetaminophen prior to each dose in cycle one, and then on day 1 of cycle two if cytokine release syndrome occurred.

Patients who achieved complete response continued treatment for eight cycles. Those who achieved partial response continued for up to 17 cycles.

Complete response rate served as the primary endpoint. Secondary endpoints included overall response rate, treatment-emergent adverse events, PFS, duration of response, time to next treatment and OS.

The efficacy analysis included 45 evaluable patients. At data cutoff, 22 had completed treatment and remained on active follow-up, 16 remained on treatment, and seven were off study. Four study participants discontinued treatment prematurely — one due to disease progression and three due to adverse events.

Median follow-up was 5.8 months and median therapy duration was 5.5 months.

Nearly all study participants (96%) responded to therapy. Three-quarters (76%) achieved complete response, 20% achieved partial response, 2% achieved stable disease and 2% had progressive disease. Most patients who achieved complete response had done so by first assessment, performed at 3 months, Falchi said.

Researchers observed responses across subgroups, including those with grade 1/grade 2 and grade 3A disease, those with or without bulky disease, and those with maximum standard uptake value of 13 or greater.

Researchers observed no new safety signals. The therapy exhibited a similar toxicity profile in the frontline setting as it did in the relapsed setting, Falchi said.

The most common treatment-emergent adverse event was injection site reaction.

More than half (57.4%) safety-evaluable patients developed cytokine release syndrome, with 29 of 31 cases being grade 1. Most CRS events occurred on cycle one day 1 (54%) or day 8 (19%).

Investigators observed no immune effector cell-associated neurotoxicity syndrome-like toxicities or tumor lysis syndrome.