ZANUBRUTINIB PLUS OBINUTUZUMAB VERSUS OBINUTUZUMAB IN PATIENTS WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA: UPDATED ANALYSIS OF THE ROSEWOOD STUDY

Introduction: In an early-phase study, the combination of zanubrutinib plus obinutuzumab (ZO) was well tolerated and associated with an early signal of efficacy in patients (pts) with follicular lymphoma (FL) (Tam et al. Blood Adv, 2020). ROSEWOOD (NCT03332017) is a phase 2, randomized study designed to assess efficacy and safety of ZO versus obinutuzumab (O) in patients with relapsed/refractory (R/R) FL. Here, we present an updated analysis with a median follow-up of 20.2 months. Methods: Pts with R/R FL (grade 1–3a) who received ≥2 lines of therapy including an anti-CD20 antibody and alkylating agent were randomized 2:1 to receive ZO or O. Zanubrutinib was given at 160 mg twice daily until progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) by independent central review. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), time to next treatment (TTNT), overall survival (OS), and safety. Results: A total of 217 patients were randomized (145 for ZO; 72 for O). Median age was 64 years. Of the 217 pts, 114 (52.5%) had a high Follicular Lymphoma International Prognostic Index (FLIPI) score at screening and 123 (56.7%) pts had high tumor burden according to Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria. Median number of prior lines of therapy was 3 (range, 2–11). A total of 114 (52.5%) pts were refractory to rituximab; 214 (98.6%) patients received prior immunochemotherapy. Prior exposure to anticancer drugs included anthracyclines (80.6%), cyclophosphamide (94.0%), and bendamustine (54.8%). ORR was 69.0% (ZO) versus 45.8% (O) (p = 0.0012). Complete response rate was 39.3% (ZO) versus 19.4% (O); 18-month DOR rate was 69.3% (ZO) versus 41.9% (O); median PFS was 28.0 months (ZO) versus 10.4 months (O) (hazard ratio [HR], 0.50 [95% CI: 0.33, 0.75]; p = 0.0007). Median TTNT was not evaluable for ZO and 12.2 months for O (HR, 0.34 [95% CI: 0.22, 0.52]; p < 0.0001). Estimated OS rate at 24 months was 77.3% (ZO) and 71.4% (O), with median OS not reached (ZO) and 34.6 months (O). Nonhematologic treatment-emergent adverse events of any grade that occurred more frequently for ZO versus O (>5% difference) were petechiae (6.3% vs. 0%) and herpes zoster infection (6.3% vs. 0%); in contrast, pyrexia (13.3% vs. 19.7%) and infusion-related reaction (2.8% vs. 9.9%) occurred more frequently in patients on O. When adjusted for duration of treatment exposure, incidences of infection and cytopenia were similar, and incidence of all grades of hemorrhage was 2.4 (ZO) versus 1.3 (O) persons per 100 person-months. Two patients in each treatment group reported major hemorrhage. Incidences of atrial fibrillation and hypertension were low and similar in both treatment arms. Conclusions: ZO demonstrated meaningful activity and a manageable safety profile in patients with heavily pretreated R/R FL, representing a potential novel therapy. Encore Abstract—previously submitted to ASCO 2023 and EHA 2023 The research was funded by: BeiGene Keywords: combination therapies, indolent non-Hodgkin lymphoma, molecular targeted therapies Conflicts of interests pertinent to the abstract P. L. Zinzani Consultant or advisory role: Secura Bio, Celltrion, Gilead, Janssen-Cilag, BMS, Servier, Sandoz, MSD, AstraZeneca, Takeda, Roche, Eusa Pharma, Kyowa Kirin, Novartis, ADC Therapeutics, Incyte, BeiGene Other remuneration: Speakers Bureau: Celltrion, Gilead, Janssen-Cilag, BMS, Servier, MSD, AstraZeneca, Takeda, Roche, Eusa Pharma, Kyowa Kirin, Novartis, Incyte, BeiGene J. Mayer Research funding: BeiGene J. Trotman Research funding: BeiGene, Janssen, PCYC, Roche, Celgene BMS, Selectar A. C. de Oliveira Consultant or advisory role: Janssen, Alexion Educational grants: Janssen K. Bouabdallah Consultant or advisory role: Roche, Takeda, Kite/Gilead Honoraria: Roche, Takeda Science Foundation, AbbVie, Kite/Gilead, Sandoz-Novartis, BeiGene Educational grants: Roche, Takeda, Kite/Gilead R. Johnson Consultant or advisory role: Kite/Gilead Honoraria: Kite/Gilead, Novartis, Takeda Other remuneration: Speakers Bureau: Kite/Gilead, Novartis A. M. Garcia-Sancho Consultant or advisory role: Roche, BMS, Kyowa Kirin, Clinigen, Eusa Pharma, Novartis, Gilead/Kite, Incyte, Lilly, Takeda, ADC Therapeutics America, Miltenyi, Ideogen, AbbVie Honoraria: BMS, Janssen, Gilead/Kite, Takeda, Eusa Pharma, Novartis Research funding: Janssen Educational grants: Gilead/Kite, Janssen, Roche, BMS M. Provencio Pulla Consultant or advisory role: BMS, Takeda, MSD, Roche Honoraria: BMS, AstraZeneca, MSD, Takeda, Janssen, Roche Research funding: BMS, Roche Educational grants: BMS, AstraZeneca, Roche, MSD M. Trněný Employment or leadership position: First Faculty of Medicine, Charles University General Hospital in Prague Consultant or advisory role: Janssen, Gilead Sciences, Takeda, Bristol-Myers Squibb, Amgen, AbbVie, Roche, MorphoSys, Incyte, Novartis, Portolla Honoraria: Janssen, Gilead Sciences, Bristol-Myers Squibb, Amgen, AbbVie, Roche, AstraZeneca, MorphoSys, Incyte, Portolla, Takeda, Novartis Educational grants: Gilead, Takeda, Bristol-Myers Squibb, Roche, Janssen, AbbVie S. E. Assouline Consultant or advisory role: Genentech-Roche, Novartis, Janssen, Amgen, BMS, Palladin labs, Pfizer Research funding: Novartis Other remuneration: Speakers Bureau: Novartis, Pfizer R. Auer Consultant or advisory role: BeiGene, Eli-Lilly Research funding: Janssen Other remuneration: Speakers Bureau: BeiGene E. Ivanoa Employment or leadership position: BeiGene Stock ownership: BeiGene P. Kim Employment or leadership position: BeiGene Stock ownership: BeiGene A. Greenbaum Employment or leadership position: BeiGene, ICON Stock ownership: BeiGene S. Huang Employment or leadership position: BeiGene Stock ownership: BeiGene R. Delarue Employment or leadership position: BeiGene Stock ownership: BeiGene C. R. Flowers Consultant or advisory role: Bayer, Gilead Sciences, Spectrum Pharmaceuticals, AbbVie, Celgene, Denovo Biopharma, BeiGene, Karyopharm Therapeutics, Pharmacyclics/Janssen, Genentech/Roche, Epizyme, Genmab, Seattle Genentics, Foresight Diagnostics, Bristol-Myers Squibb/Celgene, Curio Science, AstraZeneca, MorphoSys Stock ownership: Foresight Diagnostics, N Power Research funding: Acerta Pharma, Janssen Oncology, Gilead Sciences, Celgene, TG Therapeutics, Genentech/Roche, Pharmacyclics, AbbVie, Millennium, Alimera Sciences, Xencor, 4D Pharma, Adaptimmune, Amgen, Bayer, Cellectis, EMD Serono, Guardant Health, Iovance Biotherapeutics, Kite/Gilead, MorphoSys, Nektar, Novartis, Pfizer, Sanofi, Takeda, Ziopharm Oncology

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