Ibrutinib plus br or r‐chop in previously treated patients with follicular or marginal zone lymphoma: the phase 3 selene study

Introduction: For patients with relapsed/refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL), chemoimmunotherapy (CIT; bendamustine and rituximab [BR] or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]) is recommended by international clinical practice guidelines. However, as prognosis remains poor, particularly with repeated lines of therapy, there is still an unmet need for more effective treatment. The double-blind phase 3 SELENE study evaluated ibrutinib + BR or R-CHOP in patients with R/R FL or MZL who had received prior treatment with an anti-CD20–containing CIT regimen to determine if the addition of ibrutinib would prolong progression-free survival (PFS). Methods: Adult patients diagnosed with FL or MZL who had received ≥1 prior line of CIT were randomized 1:1 to receive 6 cycles of BR or R-CHOP plus continuous ibrutinib (560 mg) or placebo daily (until progressive disease or unacceptable toxicity). The primary end point was investigator-assessed PFS. Secondary end points included overall survival (OS), overall response rate (ORR), complete response (CR) rate, duration of response (DOR), and safety. Results: A total of 403 (FL, n = 347; MZL, n = 56) patients were randomized to ibrutinib + CIT (n = 202) or placebo + CIT (n = 201). Most patients (90.3%) received BR as background CIT. After a median follow-up of 84 months, the median PFS was 40.5 months for the ibrutinib + CIT arm and 23.8 months for the placebo + CIT arm (hazard ratio [HR], 0.806 [95% confidence interval (CI), 0.626–1.037]; p = 0.0922) (Figure). For the MZL subgroup, the median PFS was not reached for ibrutinib + CIT and 91.6 months for placebo + CIT (HR [95% CI], 0.725 [0.312–1.682]; p = 0.451). The ORR (91.6% vs. 90.5%) and CR rate (55.0% vs. 50.2%) were similar between the ibrutinib + CIT and placebo + CIT arms, respectively. Median DOR was 44.3 (95% CI, 32.9–60.0) versus 21.7 (95% CI, 17.6–32.4) months in the ibrutinib + CIT versus placebo + CIT arms, respectively. Median OS was not reached in either arm (HR [95% CI], 0.980 [0.686–1.400]; p = 0.9115). Treatment-emergent adverse events (TEAEs) of grade ≥3 were reported in 85.6% of patients in the ibrutinib + CIT arm versus 75.4% in the placebo + CIT arm. Thirteen patients in each arm experienced a TEAE leading to death. The research was funded by: Janssen Pharmaceuticals, Inc. and Pharmacyclics LLC Keywords: Combination Therapies, Indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract L. J. Nastoupil Consultant or advisory role Janssen Honoraria: Janssen Research funding: Janssen G. Hess Consultant or advisory role Abbvie, ADC-Therapeutics, AstraZeneca, BMS, Genmab, Gilead/Kite, Incyte, Janssen, Miltenyi, Novartis, Roche, and Lilly Honoraria: Abbvie, AstraZeneca, Biegene, BMS, Genmab, Gilead, Incyte, Janssen, Lilly, Roche, and Gilead/Kite Research funding: Gilead/Kite, Incyte, Janssen, Morphosys, Pfizer, Roche, and Abbvie Other remuneration: Miltenyi M. A. Pavlovsky Consultant or advisory role Janssen, Abbvie, AstraZeneca, Merch, Ascentage Pharma, and Raffo Educational grants: Roche, Janssen, AstraZeneca, and Raffo Other remuneration: Janssen, Abbvie, and AstraZeneca I. Danielewicz Honoraria: BMS, Novartis, Eli Lilly, Amgen Other remuneration: Astra Zeneca, MDS, and Novartis P. McKay Honoraria: Roche, KITE, Beigene, and BMS/Celgene, speaker honorarium from Gilead, Takeda, Janssen, Incyte F. Merli Consultant or advisory role Janssen, Gilead, MSD, Takeda, Roche, Novartis, and Incyte Educational grants: Takeda, Roche, Janssen, and Novartis W. Munakata Honoraria: CHUGAI Pharmaceutical, Nippon Shinyaku, Gilead Sciences, Eisai, BMS, SymBio, and ONO Pharmaceutical Other remuneration: Research Grants: CHUGAI Pharmaceutical, Kywowa Krin, Genmab, Janssen, Nippon Shinyaku, and ONO Pharmaceutical H. Nagai Employment or leadership position: National Hospital Organization Nagoya Medical Center Honoraria: from Janssen, Ono Pharmaceutical, BMS, Chugai Pharma, Sanofi, Celgene, Takeda, Eisai, Mundi Pharma, AstraZeneca, Novartis, Lilly, Meiji Seika Kaisha, Abbvie, GlaxoSmithKline, and Genmab Research funding: Janssen, Celgene, Abbvie, Takeda, BMS, Ono Pharmaceutical, Zenyaku Kogyo, AstraZeneca, Chugai Pharma, Solasai Pharma, Kyowa Kirin, Nippon Shinyaku, Daiichi Sankyo, and Esai M. Özcan Research funding: Abbvie, Bayer, Janssen, Roche, Takeda, MSD, Pfizer, and Acerta Educational grants: Abbvie M. Rowe Employment or leadership position: Janssen Stock ownership: Janssen R. Qin Employment or leadership position: Janssen Stock ownership: Janssen T. Henninger Employment or leadership position: Janssen Stock ownership: Janssen M. Curtis Employment or leadership position: Janssen Stock ownership: Janssen D. B. Caces Employment or leadership position: Janssen Stock ownership: Janssen C. Thieblemont Consultant or advisory role Novartis, BMC/Celgene, Roche, Incyte, Kyte/Gilead, Amgen, and Takeda G. Salles Consultant or advisory role Abbvie, Atbtherapeutics, Bayer, Beigene, BMS/Celgene, Debiopharm, Epizyme, Genentech/Roche, Genmab, Incyte, Ipsen, Janssen, Kite/Gilead, Loxo/Lilly, Molecular Partners, Morphosys, Nordic Nanovector, Novartis, Regeneron, and Takeda Stock ownership: Owkin