Long term follow‐up of untreated/relapsing MCL patients with the Ibrutinib, obinutuzumab, and venetoclax combination

Backgrounds: Targeted therapies (such as Ibrutinib and Venetoclax) have improved Mantle Cell Lymphoma (MCL) patients’ outcomes. OAsIs trial has evaluated the efficacy and toxicity of the Ibrutinib Obinutuzumab plus venetoclax combination in both R/R and untreated MCL patients (NCT02558816, Le Gouill et al. Blood 2021). In the present work, we updated the outcome of patients enrolled in OASIS trial. Methods: The OASIS trial was a 3 arms multicenter prospective phase 1/2 trial. Arm A (n = 9) enrolled R/R patients who were treated with Obinutuzumab (Obi, 1000 mg) and Ibrutinib (Ibru, 560 mg). Patients in Arm B (R/R; n = 24) and C (newly diagnosed MCL; n = 15) were treated with Obi+Ibru+Venetoclax (Ven, 400 mg). Patients’ characteristics have been described in the original manuscript. Results: In cohorts A (n = 9) and B (n = 24), overall response rates were 89% and 71%, respectively. Median Follow-ups were 71.6 and 48m, the 4-y PFS were 67% and 50%, respectively. No safety signals appeared during long term FU. Patients who progressed were treated with Bendamustine-containing regimen (6 out of 10) and one patient received Odronextamab and anti-CD22xCD3 bispecific antibodies. For Cohort C (n = 15), the median follow-up was 46m (36, 49m). Median PFS and DOR were not reached, the estimated 48m-PFS and 36m-DOR were 80% (Figure 1A). Two patients prematurely discontinued, one early PD (after 4m) and one for Adverse Event (neuropathy after 9m). The early PD patient harbored no adverse event, especially no TP53 alteration. One patient with TP53 mutation is still experiencing long-term disease control. One patient experienced atrial fibrillation and one patient had acute cardiac failure. Regarding infections, one patient died of a progressive multifocal leukoencephalopathy after the completion of treatment. Two patients prematurely discontinued the treatment, one patient had a PD at C4 and has subsequently been treated with R-CHOP, one patient relapsed after treatment completion and has been treated with Glofitamab. In all, 2 patients progressed and 1 died in arm C (PML), hence, the 4-y OS is estimated to be 93% (Figure 1B). Encore Abstract - previously submitted to EHA 2023 The research was funded by: Roche SAS supplied obinutuzumab, Janssen-Cilag supplied ibrutinib and AbbVie supplied venetoclax. Roche SAS, Janssen-Cilag and AbbVie funded the trial Keywords: aggressive B-cell non-Hodgkin lymphoma, combination therapies, targeting the tumor microenvironment Conflicts of interests pertinent to the abstract. S. Rule Employment or leadership position: AstraZeneca