SYMPATICO: Ibrutinib plus venetoclax boosts PFS in R/R mantle cell lymphoma

Ibrutinib plus venetoclax was superior to ibrutinib alone regarding progression-free survival (PFS) in participants with relapsed/refractory (R/R) mantle cell lymphoma (MCL), the primary results of the phase 3 SYMPATICO trial revealed.

The phase 3 SYMPATICO trial (NCT03112174) randomised 267 participants with R/R MCL 1:1 to the combination therapy of ibrutinib plus venetoclax or to monotherapy of ibrutinib plus placebo. Participants received the allocated therapy for 24 months. Hereafter, single-agent ibrutinib was administered. The primary endpoint was PFS and the primary results were presented by Prof. Michael Wang (University of Texas, TX, USA) [1].

At a median follow-up of 51.2 months, the primary endpoint was met: the median PFS in the experimental arm was 31.9 months, significantly outperforming the control arm (median PFS 22.1 months; HR 0.65; 95% CI 0.47–0.88; log-rank P=0.0052). This result was consistent across pre-defined subgroups. Also, the duration of response was prolonged in the experimental arm (see Figure). Moreover, the time-to-next-therapy was significantly longer in participants who were treated with the combination therapy (not reached vs 35.4 months; HR 0.60; 95% CI 0.40–0.89; P=0.0096). “For overall survival, only a numerical benefit of the combination therapy over the monotherapy could be observed at this interim analysis (44.9 vs 38.6 months; HR 0.85; 95% CI 0.62–1.19; P=0.35),” said Dr Wang.

Figure: Duration of response of ibrutinib plus venetoclax or monotherapy of ibrutinib plus placebo [1]



DOR, duration of response; Ibr, ibrutinib; Mo, months; Pbo, placebo; Ven, venetoclax. 

The safety profile of the combination regimen was consistent with the known safety profiles of each respective single agent. The rate of adverse events (AEs) leading to dose reductions was higher in the combination therapy arm than in the monotherapy arm (36% vs 22%) and the most common grade ≥3 AEs in the experimental arm were neutropenia (31%), pneumonia (13%), and thrombocytopenia (13%). The atrial fibrillation rate was 5% in both arms.

In conclusion, the addition of venetoclax to ibrutinib resulted in a favourable benefit-risk profile in participants with R/R MCL.

1. Wang M, et al. Ibrutinib combined with venetoclax in patients with relapsed/refractory mantle cell lymphoma: primary analysis results from the randomized phase 3 SYMPATICO study. Abstract LBA-2, 65^th ASH Annual Meeting, 9–12 December 2023, San Diego, CA, USA.

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Posted on 7 February, 20247 February, 2024