Palazón-Carrión et al. Page 3658

Diffuse large B-cell lymphoma (DLBCL) is recognized as a heterogeneous disease that can be cured in up to 60–70% of the cases with upfront therapy. However, relapsed/refractory DLBCL (R/R DLBCL) still represents a great clinical challenge. Palazón-Carrión and colleagues conducted an open label multicenter phase 2 trial (R2-GDP-GOTEL) testing the synergism of combination lenalidomide (LEN) and rituximab (R2) plus gemcitabine, cisplatin, dexamethasone (R2-GDP schedule) in R/R DLBCL patients, not suitable for autologous stem cell transplantation. Results suggest that LEN in combination with R-GDP (R2-GDP schedule) is an immunomodulatory treatment option with manageable toxicity and promising clinical activity, with high proportion of complete responses and favorable survival outcomes in patients with R/R DLBCL. Additionally, evolution of MDSC and Treg in peripheral blood seem an alternative for monitoring immune profiling that is related to clinical outcomes of overall survival and complete responses.

Yap et al. Page 3695

In the first-in-human phase I/II ICONIC trial, Yap and colleagues demonstrate that vopratelimab, an ICOS agonist monoclonal antibody, was well tolerated alone and with nivolumab in patients with advanced solid tumors. Vopratelimab did not confer durable, antitumor activity nor did its combination with nivolumab improve efficacy in most patients with advanced solid tumors. The prospective selection of patients with ICOS+ tumors did not enrich for antitumor responses. However, reverse translational studies led to the identification of the emergence of peripheral ICOS-hi CD4 T cells as a vopratelimab-specific pharmacodynamic biomarker. Further, a potential predictive biomarker of response to vopratelimab alone and with a PD-1 inhibitor was also identified. These findings are being prospectively evaluated in a randomized phase II non-small cell lung cancer trial.

Kennedy et al. Page 3729

Fluorescence-guided surgery using tumor-targeted contrast agents has been developed to improve the completeness of oncologic resections. Quenched activity-based probes that fluoresce after covalently binding to tumor-specific enzymes have been proposed to improve specificity, but none have been tested in humans. Kennedy and colleagues report a comprehensive preclinical evaluation and the first-in-human testing of a cathepsin activity-based probe (VGT-309) for the intraoperative imaging of lung cancer. They demonstrate the safety and feasibility of VGT-309 for localizing visually occult, non-palpable tumors in real-time during surgery. These results may be generalizable to other cancers due to cathepsin overexpression in many tumor types.

Mack et al. Page 3752

Quantitative ctDNA measurements are routinely employed clinically to identify informative biomarkers in plasma. To determine whether treatment-induced changes in ctDNA mutant allele frequencies could be used to predict long-term patient outcome, Mack and colleagues conducted a prospective study of ctDNA kinetics embedded in the afatinib-based SWOG S1403 trial of treatment-naïve, EGFR-mutant advanced NSCLC. Complete clearance of EGFR mutations in ctDNA by 8 weeks was associated with significantly and substantially improved progression-free survival and overall survival compared with those with residual ctDNA at this timepoint. This algorithm outperformed RECIST and other methods for identifying patients with suboptimal outcome on EGFR TKI.