Multikine (Leukocyte Interleukin Injection) + CIZ neoadjuvant immune conditioning cuts death risk in PD-L1–low, node-negative LA OSCC

Leukocyte Interleukin Injection (LI; “Multikine”) is a locally delivered cytokine-based immunotherapy given pre-operatively and paired with CIZ (low-dose IV cyclophosphamide + indomethacin + zinc/multivitamins) to modulate immunity ahead of definitive surgery and adjuvant RT/CRT. In the randomized Phase 3 IT-MATTERS trial (NCT01265849; EudraCT 2010-019952-35) in treatment-naïve stage III/IVa oral cavity/soft-palate SCC, LI+CIZ+SOC improved OS vs SOC in a prespecified “low-risk” subset defined by cN0 and tumor PD-L1 TPS<10% (HR 0.26, p=0.0023) with supporting PFS benefit (HR 0.43, p=0.0178) and a reported 32% absolute OS advantage at 60 months; by comparison, contemporary SOC for resectable locally advanced oral cavity SCC (surgery → adjuvant RT±cisplatin) typically yields ~50% 3-year OS in large real-world datasets, with 5-year OS often still <50% in higher-risk series. Notable caveat: the “unselected LR” analysis was borderline by Cox modeling (HR 0.64, p=0.0569) despite a significant log-rank test (p=0.0340), and the biggest effect emerges after applying the cN0/PD-L1<10 enrichment—so the clinical value hinges on how strictly and reproducibly that biomarker/clinical subset is defined in practice.