IR-2

Relapsed or refractory mantle cell lymphoma (R/R MCL) remains difficult to treat, with outcomes dependent on the treatment regimen and remission duration after first‐line therapy. Several non‐chemotherapeutic regimens are under evaluation in R/R, but few studies report long‐term outcomes. In this study, we present the long‐term outcomes of the 50 patients treated with ibrutinib, lenalidomide, and rituximab (IR2) in the Nordic Lymphoma Group MCL6 Philemon phase 2 trial. Survival outcomes were compared with a matched cohort from the Swedish MCLcomplete study. After 5 years, 14 patients (28%) remained relapse‐free, including one with a TP53 mutation. The median progression‐free survival (PFS) was 17.4 months, with the longest PFS of 8.1 years. Thirty‐two patients had died, primarily from MCL (72%). Poorer survival was associated with intermediate or high‐risk Mantle Cell Lymphoma International Prognostic Index and impaired health‐related quality of life (HRQoL). While TP53 mutations (n = 11) did not significantly impact survival, a trend toward poorer outcomes was observed in multivariable Cox regression analyses (PFS hazard ratio: 2.09, 95% confidence interval: 0.95–4.62, p = 0.068). The IR2 regimen demonstrated superior survival compared to the MCLcomplete cohort both before and after matching. In conclusion, this study highlights the role of non‐chemotherapeutic agents in R/R MCL and demonstrates the prognostic impact of HRQoL on overall survival. Although IR2 showed initial activity in TP53‐mutated patients, it did not completely overcome their poor prognosis. However, the IR2 regimen may serve as a bridge to allogeneic stem cell transplantation or chimeric antigen receptor T‐cell therapy.

Malignant tumors continue to be the most common and remain one of the leading causes of death with increasing incidence, mortality, and burden. Traditional chemotherapeutic agents often encounter significant side effects and demonstrate lackluster efficacy. Photodynamic therapy (PDT) is widely recognized as a microtrauma therapeutic method for tumor treatment technique. Ir(III) complexes are a potential photosensitizer (PS) type due to their excellent photophysical properties. Ir-1 and Ir-2, which are two novel Ir(III) complexes were synthesized and characterized using spectroscopic and electrochemical techniques, the key structural difference lies in the position of a benzene in the C^N ligand. This slight change makes Ir-2 have a better intersystem crossing (ISC) ability and thus has more excellent triplet excited state properties. So Ir-2 shows high singlet oxygen (¹O₂) production and photocytotoxicity with half maximal inhibitory concentration (IC₅₀) of 40 nM, effectively inhibiting and eliminating tumors in mice while demonstrating good biosafety. This study highlights the importance of precise molecular design in developing highly efficient PSs for PDT.