24P Is molecular characterization useful for targeted therapy orientation in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) included in early phase clinical trials?

Early drug development is associated with a high rate of failure in patients with R/R DLBLC, partly due to high genomic heterogeneity. We herein evaluate the potential outcome benefit of a targeted molecular characterization for treatment orientation in patients with R/R DLBCL prior to enrollment in early phase clinical trials (eaCT). From 2013 to 2020, paired target next generation sequencing (NGS), using a customized panel of 44 genes (IonTorrent) was performed for all patients with R/R DLBCL and biopsied at time of enrollment in eaCT. Molecular alterations were classified according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT scale; J. Mateo, Annals of Oncology, 2018). For outcome analysis, patients were classified as molecularly oriented (MO, i.e. treated based on the presence of an ESCAT actionable molecular abnormalities) or non-molecularly oriented (no-MO). Over the study period, ninety pts with R/R DLBCL screened for early clinical trial had their tumor & germline samples sequenced. The mean age was 62 years (range 23-83) and median prior lines of therapies was 2 (range 1-9). Sixteen (18%) pts were enrolled in eaCT and treated with MO drugs, 43 (48%) pts were enrolled in eaCT and treated with no-MO drugs, and 31 (34%) pts were not enrolled in eaCT. At enrollment, the main clinical and laboratory characteristics (age, gender, Ann-Arbor stage, performance status, median prior lines, LDH, albumin) were similar in MO and non-MO treated patients. In MO and no-MO patients, median PFS were 3.3 months and 1.7 months, respectively (p=0.0092; HR=0.47 [CI95:0.27-0.83]); and median OS were 20.0 and 6.7 months, respectively (p=0.0238; HR=0.49 [CI95: 0.26-0.91]). Molecular orientation before inclusion in eaCTs seems to be associated with better outcome in patients with R/R DLBCL. These data support the value of a target molecular characterization prior to eaCT enrollment and may increase the chances of a precision investigated drug being effective for R/R DLBCL.