MULTIPLY

The randomized phase III TRIANGLE trial of the European MCL network is the most extensive study ever conducted in MCL.

The trial evaluated the addition of ibrutinib to a standard ASCT-containing treatment (arm A+I) compared to a standard treatment (arm A) and to an ibrutinib-containing treatment without ASCT (arm I).

870 patients from 13 countries with untreated stage II-IV MCL were enrolled. At 31 months of follow-up, significantly more patients in both ibrutinib arms responded to therapy. They remained disease-free, establishing a new standard of care, substituting the more toxic ASCT with a 2-year better tolerated targeted therapy.

The study included regular MRD analyses with the collection of baseline and multiple follow-up samples, generating an extensive tissue and plasma collection for translational studies. Moreover, FFPE tissues from most patients are available for additional histopathological testing. Therefore, TRIANGLE is a unique opportunity for multilayer characterization of a large patient cohort treated with the new standard of care. MULTIPLY will generate and validate an integrative model of various clinical-biological baseline and dynamic follow-up parameters. Based on functional analysis, we will also identify potential new therapeutic targets.

MULTIPLY is structured into three major interconnected work packages (WP):

(1) Identification of clinical predictors, characterization of relapses, and salvage treatment (Clinical project);

(2) Identification of lymph node-derived predictors (Lymph node WP);

(3) Evaluation of biological predictors based on PB, BM, and cfDNA (Liquid tissue WP).

All information will be integrated to generate a multilayer prediction model incorporating all available clinical and biological markers.