# Long-term outcomes of venetoclax and ibrutinib in Japanese patients with relapsed/refractory mantle cell lymphoma

## TL;DR

This study shows that the drug combination of ibrutinib and venetoclax is effective and safe for Japanese patients with relapsed or refractory mantle cell lymphoma over the long term.

## Contribution

The study provides updated long-term efficacy and safety data for ibrutinib plus venetoclax in Japanese patients with mantle cell lymphoma.

## Key findings

- The overall response rate was 83%, with all responses being complete.
- Most patients achieved undetectable minimal residual disease after treatment.
- The treatment was well-tolerated with no treatment-related deaths.

## Abstract

Patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) face a poor prognosis in the absence of effective treatment options. Ibrutinib plus venetoclax demonstrated high response rates and a tolerable safety profile in the primary analysis of the Phase 2, M20-075 study (NCT04477486) in Japanese patients with R/R MCL. We report updated efficacy and safety from this study with longer follow-up.

Patients received 560 mg ibrutinib and 400 mg venetoclax (5-week ramp-up to 400 mg) once daily for up to 104 weeks followed by ibrutinib monotherapy. Primary endpoint was Independent Review Committee-assessed complete response (CR) rate. Secondary endpoints included overall response rate (ORR), duration of response (DOR), undetectable minimal residual disease (uMRD) in patients achieving CR, progression-free survival (PFS), overall survival (OS), and safety.

After a median follow-up of 37.2 months, 13 patients had received ibrutinib plus venetoclax, 8 (62%) remained on ibrutinib monotherapy, and 9 (69%) completed 24 months of venetoclax. ORR was 83% (10/12 [per-protocol population]; all CR); median DOR was not reached. All 6 patients positive for MRD at baseline who achieved CR had uMRD. Median PFS and OS were not reached. Most frequent Grade ≥ 3 treatment-emergent adverse events (TEAEs) were neutropenia (46%) and leukopenia (23%); one TEAE leading to treatment discontinuation was squamous cell carcinoma unrelated to treatment. There were no cases of tumor lysis syndrome or TEAEs leading to death.

Long-term follow-up of ibrutinib plus venetoclax showed prolonged efficacy and a well-tolerated safety profile in Japanese patients with R/R MCL.

The online version contains supplementary material available at 10.1007/s10147-025-02865-4.