5-y Follow-up of Combination of Ibrutinib, Obinutuzumab and Venetoclax for Patients with Newly Diagnosed Mantle Cell Lymphoma, the Oasis Trial

Background:

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, especially for patients with newly diagnosed MCL.

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, 1000mg) and Ibrutinib (Ibru, 560mg). Patients in Arm B (R/R; n=24) and C (newly diagnosed MCL; n=15) were treated with Obi+Ibru+Venetoclax (Ven, 400mg). Patients’ characteristics have been described in the original manuscript.

Results:

In R/R cohorts A (n=9) and B (n=24), overall response rates were 89% and 71%, respectively. Median Follow-ups were 72 and 58 m, the 6-y PFS were 53% and 40%, 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), all patients presented with a medium or high-risk MIPI, the median follow-up was 61 m (48-68m). The overall response rate was 93%, with 87% of CR. Median PFS and DOR were not reached, the estimated 60m-PFS and DOR were 80%. 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 disease control. One patient experienced atrial fibrillation and one patient had acute cardiac failure. Regarding infections, one patient died of a progressive multifocal leukoencephalopathy (PML) 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 5-y OS is 93%.

Conclusion:

The Ibrutinib-Venetoclax-Obinutuzumab triplet is associated with a highl and sustained disease control in newly diagnosed (5y-PFS of 80%) patients presenting with high risk-profiles. The anti-CD20+Ibrutinib vs anti-CD20+Ibrutinib+Venetoclax combinations are currently under investigation in OASIS-II trial (NCT04802590) for untreated patients with MCL and may represent a bona-fide alternative to Chemo-based treatments.