Introduction:

Chemoimmunotherapy is a standard initial treatment for patients (pts) with high-tumor burden follicular lymphoma (FL), but it is associated with significant toxicity, including prolonged immune suppression, infections, and secondary malignancies. Pts with FL would benefit from alternative chemotherapy-free treatment options that are effective and well-tolerated. Glofitamab (glofit) is a CD3xCD20 bispecific antibody that has demonstrated high response rates in pts with relapsed/refractory FL, albeit with relatively frequent grade 2 or higher cytokine release syndrome (CRS) (17-26%) in an initial phase II study (Morschhauser, ASH abstract 2021). We hypothesized that pre-treatment with 4 weekly doses of obinutuzumab (obin) before glofit initiation could lower the risk of CRS and also deepen responses by targeting CD20 via a distinct mechanism of action. Here, we present initial results of a phase II, investigator-initiated, multicenter trial of time-limited therapy with glofit and obin (GLOBIN) (NCT05783596) for pts with previously untreated, high-tumor burden FL.

Methods:

Key eligibility criteria include previously untreated grade 1-3A FL, age ≥ 18, stage II-IV, requirement for therapy based on modified GELF criteria, and ECOG PS 0-2. (Enrollment to a separate marginal zone lymphoma cohort is ongoing with results to be reported separately). During cycle 1, pts receive obin on days -21, -14, -7, and 0 followed by standard glofit step-up dosing (2.5 mg on day 1, 10 mg on day 8, and 30 mg on cycle 2 day 1). Glofit continues on day 1 for cycles 3-12. Pts are admitted for observation for 24 hours after the first dose of glofit. Responses are evaluated based on Lugano 2014 criteria using PET-CT after 3, 7, and 12 cycles.

Results:

35 pts were enrolled between 8/2023 and 4/2025. The median age was 63 (range 42-78) and 46% of pts were female. At study entry, 30 pts (86%) had stage IV, 6 (17%) grade 3A FL, 9 (26%) bulky disease (≥7 cm), and 22 (63%) a FLIPI score of 3-5.

Among 34 response-evaluable pts (with 1 pt awaiting first response assessment), the best objective and complete metabolic response (CMR) rates were 100% (95CI 90-100%) and 88% (95CI 73-97%), respectively. Among 4 pts with a best response of a partial response, 3 have only had a single response assessment and continue on treatment. To date, a single pt has progressed with a biopsy demonstrating CD20-negative FL. With a median follow-up of 7.6 months (range 1.1-20.1), the 8-month PFS is 95% (95CI 85-100%). No pt has died.

CRS occurred in 14 pts (40%), 13 with G1 (37%) and 1 with G3 (3%). G3 CRS (fever, hypoxia) developed in a pt with lung involvement by lymphoma and resolved rapidly (<24 hours) after administration of dexamethasone and tocilizumab. Infections occurred in 11 pts (31%), all grade 1-2 (G1 9%, G2 23%). Other common treatment-related adverse events (trAEs) included infusion-related reactions (all related to obin) (49%), neutropenia (31%), cough (26%), fatigue (26%), diarrhea (23%), pruritus (23%), headache (20%), myalgia (20%), and rash (20%). G3 trAEs include neutropenia (G3 14%, G4 3%), lymphopenia (9%), infusion-related reaction (6%), increased ALT (6%), increased AST (3%), and diarrhea (3%). No pts have discontinued treatment due to AEs.

Peripheral blood mononuclear cells were collected for analysis by flow cytometry to profile T/NK/B cell compartments at screening (C1D-21), C1D1, C1D8, C2D1, and progression (when relevant). Analyses to describe treatment-induced changes and identify immune populations associated with response and toxicity are ongoing and will be presented at the meeting.

Conclusion:

Glofit and obin has a manageable safety profile and is associated with high CMR rates among pts with previously untreated, high-tumor burden FL. Pre-treatment with 4 doses of obin appears to reduce the risk of CRS with no cases of G2 and 1 case of G3 CRS observed among 35 patients. These results support further exploration of glofit in FL.

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2025
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