Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
J Clin Oncol. 2022 Jan 10;40(2):202-212. doi: 10.1200/JCO.21.01797. Epub 2021 Nov 19.
Most patients with mantle cell lymphoma (MCL) are older. In this study, we investigated the efficacy and safety of a chemotherapy-free combination with ibrutinib and rituximab (IR) in previously untreated older patients with MCL (age ≥ 65 years).
We enrolled 50 patients with MCL in this single-institution, single-arm, phase II clinical trial (NCT01880567). Patients with Ki-67% ≥ 50% and blastoid morphology were excluded. Ibrutinib was administered with rituximab up to 2 years with continuation of ibrutinib alone. The primary objective was to assess the overall response rate and safety of IR. In evaluable samples, whole-exome sequencing and bulk RNA sequencing from baseline tissue samples were performed.
The median age was 71 years (interquartile range 69-76 years). Sixteen percent of patients had high-risk simplified MCL international prognostic index. The Ki-67% was low (< 30%) in 38 (76%) and moderately high (≥ 30%-50%) in 12 (24%) patients. The best overall response rate was 96% (71% complete response). After a median follow-up of 45 months (interquartile range 24-56 months), 28 (56%) patients came off study for various reasons (including four progression, 21 toxicities, and three miscellaneous reasons). The median progression-free survival and overall survival were not reached, and 3-year survival was 87% and 94%, respectively. None of the patients died on study therapy. Notably, 11 (22%) patients had grade 3 atrial fibrillation. Grade 3-4 myelosuppression was seen in < 5% of patients. Differential overexpression of , , , , , and was noted in partial responders compared with patients with complete response.
IR combination is effective in older patients with MCL. Baseline evaluation for cardiovascular risks is highly recommended. Randomized trial is needed for definitive conclusions.
大多数套细胞淋巴瘤（MCL）患者年龄较大。在这项研究中，我们研究了伊布替尼联合利妥昔单抗（IR）在未经治疗的老年（年龄≥65 岁）MCL 患者中的疗效和安全性。
我们在这项单中心、单臂、II 期临床试验（NCT01880567）中招募了 50 名 MCL 患者。排除 Ki-67%≥50%和母细胞样形态的患者。伊布替尼联合利妥昔单抗治疗 2 年，随后单独使用伊布替尼。主要目的是评估 IR 的总体缓解率和安全性。在可评估的样本中，从基线组织样本中进行全外显子组测序和批量 RNA 测序。
中位年龄为 71 岁（四分位距 69-76 岁）。16%的患者有高危简化 MCL 国际预后指数。38 例（76%）患者的 Ki-67%较低（<30%），12 例（24%）患者的 Ki-67%中等偏高（≥30%-50%）。最佳总体缓解率为 96%（71%完全缓解）。中位随访 45 个月（四分位距 24-56 个月）后，28 例（56%）患者因各种原因退出研究（包括 4 例进展、21 例毒性和 3 例其他原因）。中位无进展生存期和总生存期均未达到，3 年生存率分别为 87%和 94%。没有患者死于研究治疗。值得注意的是，11 例（22%）患者有 3 级心房颤动。<5%的患者出现 3-4 级骨髓抑制。与完全缓解患者相比，部分缓解患者的 、 、 、 、 和 表达存在差异。
IR 联合方案在老年 MCL 患者中有效。强烈建议对心血管风险进行基线评估。需要进行随机试验以得出明确结论。
