Intrapatient Comparative Analysis of Zanubrutinib Plus Obinutuzumab Efficacy in
Relapsed/Refractory Follicular Lymphoma Using the Growth Modulation Index
Krimo Bouabdallah,1 Shanmei Liao,2 Richard Delarue,3 Laura Dima,4 Dirk Weber,3 Laurent Dumartin4
1Hôpital Haut-Lévêque, CHU Bordeaux, Pessac, France; 2BeiGene Co, Ltd, Shanghai, China;
3BeiGene Switzerland, GmbH, Basel, Switzerland; 4BeiGene, Paris, France

Background: Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma.
ROSEWOOD (NCT03332017), a global, randomized, open-label phase 2 study, compared theefficacy and safety of zanubrutinib plus obinutuzumab (ZO) with obinutuzumab (O) alone in patientswith relapsed/refractory (R/R) FL who had received ≥2 prior lines of systemic therapy. Medianprogression-free survival (PFS) was longer with ZO vs O (28.0 months [95% CI, 16.1-not evaluable{NE}] vs 10.4 months [95% CI, 6.5-13.8]; HR, 0.50 [95% CI, 0.33-0.75]; P<.001) and comparedfavorably with PFS with the last prior treatment (12.1 months) (Zinzani et al. JCO; 2023). The absenceof clear consensus for standard of care in R/R FL and the heterogeneity of patient populations
included in trials limit the possibility of indirect comparisons across different studies. To overcome thischallenge, the Growth Modulation Index (GMI) uses each patient as their own control to evaluate theefficacy of treatments by comparing PFS durations with successive treatments. A GMI >1 indicatesthat the present treatment extends the PFS duration vs the previous treatment, and a GMI ≥1.33 isoften used as a threshold for significant clinical activity.
Aims: To analyze the efficacy of ZO in the sequence of treatment received by patients included in theROSEWOOD study, we performed an intrapatient comparison analysis using the GMI clinicalendpoint.
Methods: PFS was assessed by independent central review (ICR) and censoring rules were definedin the ROSEWOOD study. GMI was defined as (PFSn from ZO or O)/(PFSn−1 from last prior line). The
distribution, including the median and the proportion within each interval, of GMI was estimated using
the Kaplan-Meier (KM) method. The 95% CIs for median GMI were estimated using the Brookmeyer
and Crowley method, and the 95% CIs for the proportion within each interval were estimated using
Greenwood's formula with logit transformation.
Results: In ROSEWOOD, 145 patients were randomized to the ZO arm and 72 to the O arm. Five
patients were excluded from the GMI analysis in the ZO arm and 3 in the O arm, as no PFSn−1 data
were available. PFS analysis of the KM curves confirmed previous observations that median PFS withZO, but not with O, was longer compared with the last prior treatment (ZO, 28.0 vs 12.1; O, 10.4 vs11.5 months), the most frequent of which were rituximab-containing regimens (ZO, 69%; O, 60%) andimmunochemotherapy (ZO, 54%; O, 51%). In the overall population, median GMI was 2.7 (95% CI,1.6-4.9) in the ZO arm (Figure) and 0.9 (95% CI, 0.5-1.7) in the O arm. In the ZO arm, 63.3% (95%CI, 53.8-71.9) of patients had a GMI ≥1.33, and 34.1% (95% CI, 25.9-43.3) had a GMI <1. Subgroup
analysis showed that patients in the ZO arm with 2 prior lines (n=63) had a median GMI of 2.5 (95%CI, 0.9-NE), with 65.6% (95% CI, 50.8-77.8) of patients having a GMI ≥1.33. Patients in the ZO armwith >2 prior lines (n=77) had a median GMI of 3.1 (95% CI, 1.3-4.9), with 61.8% (95% CI, 49.2-73.0)
of patients having a GMI ≥1.33.
Summary/Conclusion: In this study, GMI allowed the generation of comparative efficacy evidence
for ZO in R/R FL. Post hoc GMI analysis of data from ROSEWOOD showed that the majority (>60%)
of patients with R/R FL receiving ZO had a significant (GMI ≥1.33) improvement in PFS vs their lastprior treatment, irrespective of the number of prior treatments. The median GMI of 2.7 in the overall
population was more than double the 1.33 threshold for meaningful clinical activity compared with thelast prior treatment. These data further support the benefit of ZO as a novel treatment option forpatients with R/R FL.

EHA 2024

EHA 2024