TRIANGLE: Noninvasive genotyping and MRD responses with ibrutinib combination therapy in MCL

Results from an analysis of the phase III TRIANGLE trial (NCT02858258; N = 870), assessing ibrutinib + immunotherapy vs immunotherapy alone in 57 younger patients with advanced-stage mantle cell lymphoma (MCL), were published by Khouja et al. in Leukemia. 

The study utilized cell-free (cf) DNA for noninvasive genotyping and measurable residual disease (MRD) assessment, comparing circulating tumor (ct) DNA and circulating tumor cell (CTC) dynamics across treatment arms.

Key data: High pretreatment cfDNA and ctDNA levels were associated with inferior overall survival (OS) (hazard ratio [HR], 3.42; p = 0.043 and HR 4.33; p = 0.0134, respectively). Ibrutinib + immunotherapy demonstrated enhanced MRD clearance compared with immunochemotherapy alone at interim staging (CTC: 71% vs 57%; ctDNA: 59% vs 24%). MRD-positivity by quantitative polymerase chain reaction (qPCR) at the end of induction significantly predicted inferior failure-free survival (FFS) (HR, 8.26; p < 0.0001) and OS (HR, 7.33; p = 0.0005). Ibrutinib + first-line immunotherapy vs immunotherapy alone appeared to mitigate TP53 mutated-mediated risk (HR, 1.9 vs 10).

Key learning: Ibrutinib combined with immunotherapy induces rapid MRD response in younger patients with MCL, potentially through enhanced tumor cell mobilization and immune system reconstitution.