Mantle cell lymphoma (MCL) is a rare, incurable lymphoma subtype characterized by heterogeneous outcomes. To better understand the clinical behavior and response to treatment, predictive biomarkers are needed. Using residual archived material from patients enrolled in the MCL3001 (RAY) study, we performed detailed analyses of gene expression and targeted genetic sequencing. This phase III clinical trial randomized patients with relapsed or refractory MCL to treatment with either ibrutinib or temsirolimus. We confirmed the prognostic capability of the gene expression proliferation assay MCL35 in this cohort treated with novel agents; it outperformed the simplified MCL International Prognostic Index in discriminating patients with different outcomes. Regardless of treatment arm, our data demonstrated that this assay captures the risk conferred by known biological factors, including increased MYC expression, blastoid morphology, aberrations of TP53, and truncated CCND1 3′ untranslated region. We showed the negative impact of BIRC3 mutations/deletions on outcomes in this cohort and identified that deletion of chromosome 8p23.3 also negatively impacts survival. Restricted to patients with deletions/alterations in TP53, ibrutinib appeared to abrogate the deleterious impact on outcome. These data illustrate the potential to perform a molecular analysis of predictive biomarkers on routine patient samples that can meaningfully inform clinical practice.

套细胞淋巴瘤 (MCL) 是一种罕见的、无法治愈的淋巴瘤亚型，其特点是结果异质。为了更好地了解临床行为和对治疗的反应，需要预测性生物标志物。我们使用参加 MCL3001 (RAY) 研究的患者的剩余存档材料，对基因表达和靶向基因测序进行了详细分析。这项 III 期临床试验将复发性或难治性 MCL 患者随机分配接受依鲁替尼或替西罗莫司治疗。我们证实了基因表达增殖试验 MCL35 在这个用新药物治疗的队列中的预后能力；它在区分具有不同结果的患者方面优于简化的 MCL 国际预后指数。无论治疗臂如何，MYC表达、胚状体形态、TP53畸变和截短的CCND1 3 ' 非翻译区。我们展示了BIRC3突变/缺失对该队列结果的负面影响，并确定染色体 8p23.3 的缺失也会对生存产生负面影响。仅限于TP53缺失/改变的患者，依鲁替尼似乎消除了对结果的有害影响。这些数据说明了对常规患者样本进行预测性生物标志物分子分析的潜力，这可以为临床实践提供有意义的信息。