How Effective Is the Ibrutinib-Venetoclax-Obinutuzumab Triplet in Mantle Cell Lymphoma?

In a recent prospective, multicenter phase 1/2 trial presented at the 66th American Society of Hematology Annual Meeting & Exposition in San Diego, CA, the combination of ibrutinib, venetoclax, and obinutuzumab demonstrated high rates of durable disease control in patients with newly diagnosed mantle cell lymphoma (MCL). Findings from the OASIS trial showed an estimated 5-year progression-free survival (PFS) rate of 80% and overall survival (OS) of 93%.

While chemotherapy has traditionally been the standard treatment approach for patients with MCL, newer targeted therapies like ibrutinib and venetoclax have shown promise. This study aimed to evaluate whether a triplet regimen of ibrutinib, venetoclax, and obinutuzumab could provide effective and durable disease control for newly diagnosed patients with MCL.

In the study, patients newly diagnosed with MCL (N = 15) received a combination treatment of obinutuzumab (1000 mg), ibrutinib (560 mg), and venetoclax (400 mg). The median follow-up was 61 months (range, 48-68 months). Patient risk was assessed using the MCL International Prognostic Index (MIPI), with all participants classified as medium or high risk.

The study reported an overall response rate (ORR) of 93%, with 87% of patients achieving a complete response (CR). Median PFS and duration of response (DOR) were not reached at the time of analysis, with estimated 5-year PFS and DOR rates of 80%. Two patients discontinued treatment prematurely due to early progression (n = 1) and adverse events (n = 1). Adverse events included neuropathy, atrial fibrillation, and acute cardiac failure, with one patient succumbing to progressive multifocal leukoencephalopathy (PML) post-treatment. Of the two patients who progressed, one had no TP53 alterations and relapsed early, while another with a TP53 mutation maintained disease control.

“The ibrutinib-venetoclax-obinutuzumab triplet is associated with a high and sustained disease control in newly diagnosed (5y-PFS of 80%) patients presenting with high risk-profiles,” the study authors concluded.

Reference

Tessoulin B, Morschhauser F, Chiron D, et al. 5-y follow-up of combination of Ibrutinib, Obinutuzumab, and Venetoclax for patients with newly diagnosed mantle cell lymphoma, the OASIS trial. Paper presented at: American Society of Hematology Annual Meeting; December 7, 2024; San Diego, CA. Accessed November 26, 2024. https://ash.confex.com/ash/2024/webprogram/Paper206778.html.