TREATMENT OF NEWLY-DIAGNOSED FOLLICULAR LYMPHOMA WITH RITUXIMAB, GOLCADOMIDE +/- NIVOLUMAB- INTERIM ANALYSIS OF THE PHASE II TOP-FLOR STUDY

Abstract

Background: Standard rituximab (R) +lenalidomide (R2) or chemoimmunotherapy is effective in treatment-naïve follicular lymphoma (TN FL) but is associated with Grade 3–4 AE rates > 65% with elderly patients (pts) overrepresented. Golcadomide (Golca) is a potent first-in-class oral Cereblon E3 Ligase Modulator (CELMoD) with dual immunomodulatory and anti-tumor activity 10- to 100-fold enhanced compared to lenalidomide, preferential lymphoid organ distribution and a favourable toxicity profile (Chavez ASH 2024; Amzallag ASH 2024). R-Golca yields responses in 93% relapsed FL. We have demonstrated immune augmentation, safety and efficacy of PD1/PDL1i nivolumab (N) +rituximab, and atezolizumab-obinutuzumab-radiotherapy in TN FL (Chong ASCO 2024; Barraclough Blood Adv 2025). We describe here the interim analysis of a randomised phase II study of R-Golca +/- N in stage II-IV, Grade 1–3A TN FL. (Chong ASCO 2024)

Methods: TOP-FLOR (NCT05788081) is an investigator-led multicentre randomised open label umbrella Baysian Optimal Phase II trial in TN FL. Up to 40pts will be randomised 1:1 to receive 8 cycles of induction therapy Q4W: R (375 mg/m² IV, D1), Golca (0.4 mg p.o daily, D1–14) +/- N (480 mg IV, D1) and 2 years of R maintenance (Q12W). The primary endpoint is rate of Complete Metabolic Response (CMR) in the absence of cessation due to prohibitive toxicity (CTCAE V5.0) following induction. Interim efficacy analysis (PET/CT Lugano response) in the first 22 pts was pre-planned, with a predefined futility threshold of 7/11 CMR (63.6%) in each arm.

Results: The interim analysis included 22 enrolled pts (11 per arm). Median age was 64.5y (range 49–77) with 68% male. CMR rate at the end of induction was 82% (18/22; 95% CI: 60%, 95%), CMR rate by arm in the futility cohort, was: 10/11 (92%) R-Golca and 8/11 (73%) R-Golca+N with 1 permanently ceasing due to Gr4 sepsis in cycle 1, unrelated to therapy and 1 ceasing due to disease progression (Figure 1). Proportion of pts experiencing an AE during induction were: 100% Gr1, 82% Gr2, 64% Gr3, 9% Gr4 (2pt). Most frequent of any grade were infection (77%; 95% CI: 54%–92% [Gr3 14%]), neutrophil count decrease (63%; 95% CI: 40–82% [Gr3+ 92%; plus 2 pt Gr3 febrile neutropenia]; 10pts received G-CSF) and maculo-papular rash (45%; 95% CI: 24%–67%—all in pts who had bactrim & allopurinol which resolved on cessation of allopurinol); 2 pts R-Golca +N arm and 1 pt in the R-Golca arm had Golca dose reduction to 0.3 mg due to adverse events. 18/22 remain on treatment. Interim results reached the threshold for continued recruitment in both arms.

Conclusions: This is the first study to demonstrate that Rituximab-golcadomide +/-nivolumab is a highly effective combination therapy in TN FL with manageable toxicity, most commonly neutropenia and infection. Differences between arms could not be elucidated in this preplanned interim analysis. The study continues recruitment.

Research funding declaration: This trial is supported by an investigator-sponsored research grant from Bristol-Myers Squibb. Nivolumab and golcadomide supplied by Bristol-Myers Squibb.

Keywords: combination therapies; indolent non-Hodgkin lymphoma; ongoing trials

Potential sources of conflict of interest:

G. Chong

Other remuneration: Grant funding: Bristol-Myers Squibb

C. Keane

Other remuneration: Grants- Bristol-Myers Squibb

E. A. Hawkes

Consultant or advisory role: Bristol-Myers Squibb

Other remuneration: Grant funding: Bristol-Myers Squibb