Forsgren Elin, Jørgensen Rasmus R K, Bentzen Hans, Riise Jon, Haaber Jacob, Pasanen Annika, Kuitunen Hanne, Wader Karin F, El-Galaly Tarec C, Hutchings Martin, Glimelius Ingrid, Jerkeman Mats
Department of Immunology, Genetics and Pathology Uppsala University Uppsala Sweden.
Department of Internal Medicine Örnsköldsvik Hospital Örnsköldsvik Sweden.
Hemasphere. 2025 Mar 18;9(3):e70101. doi: 10.1002/hem3.70101. eCollection 2025 Mar.
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 MCL study. After 5 years, 14 patients (28%) remained relapse-free, including one with a 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 mutations ( = 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, = 0.068). The IR2 regimen demonstrated superior survival compared to the MCL 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.
复发或难治性套细胞淋巴瘤（R/R MCL）的治疗仍然困难，其治疗结果取决于治疗方案和一线治疗后的缓解持续时间。几种非化疗方案正在R/R MCL中进行评估，但很少有研究报告长期结果。在本研究中，我们展示了北欧淋巴瘤组MCL6腓利门2期试验中50例接受伊布替尼、来那度胺和利妥昔单抗（IR2）治疗的患者的长期结果。将生存结果与瑞典MCL研究中的匹配队列进行比较。5年后，14例患者（28%）无复发，其中1例有 突变。中位无进展生存期（PFS）为17.4个月，最长PFS为8.1年。32例患者死亡，主要死于MCL（72%）。较差的生存与中危或高危套细胞淋巴瘤国际预后指数以及健康相关生活质量（HRQoL）受损有关。虽然 突变（ = 11）对生存没有显著影响，但在多变量Cox回归分析中观察到预后较差的趋势（PFS风险比：2.09，95%置信区间：0.95 - 4.62， = 0.068）。IR2方案在匹配前后与MCL队列相比均显示出更好的生存情况。总之，本研究强调了非化疗药物在R/R MCL中的作用，并证明了HRQoL对总生存的预后影响。虽然IR2在TP53突变患者中显示出初始活性，但并未完全克服其不良预后。然而，IR2方案可作为异基因干细胞移植或嵌合抗原受体T细胞疗法的桥梁。
