Background: Mantle cell lymphoma (MCL) is a rare malignancy with heterogeneous behavior. Despite the therapeutic advances recently achieved, MCL remains incurable. Currently, the standard of care for young and fit patients involves induction immunochemotherapy followed by up-front autologous stem cell transplantation (ASCT). However, the role of more intensive induction regimens, such as those based on high doses of cytarabine (HDAC), remains controversial in the management of ASCT-eligible patients. Methods: This retrospective, observational, and single-center study involved 165 MCL patients treated at the largest oncology center in Latin America from 2010 to 2022. We aimed to assess outcomes, determine survival predictors, and compare responses between different primary therapeutic strategies, with a focus on assessing the impact of HDAC-based regimens on outcomes in ASCT-eligible patients. Results: The median age at diagnosis was 65 years (38–89 years), and 73.9% were male. More than 90% of the cases had a classic nodal form (cnMCL), 76.4% had BM infiltration, and 56.4% presented splenomegaly. Bulky ≥ 7 cm, B-symptoms, ECOG ≥ 2, and advanced-stage III/IV were observed in 32.7%, 64.8%, 32.1%, and 95.8%, respectively. Sixty-four percent of patients were categorized as having high-risk MIPI. With a median follow-up of 71.1 months, the estimated 2-year OS and EFS were 64.1% and 31.8%, respectively. Patients treated with (R)-HDAC-based regimens had a higher ORR (85.9% vs. 65.7%,p= 0.007) compared to those receiving (R)-CHOP, as well as lower POD-24 rates (61.9% vs. 80.4%,p= 0.043) and lower mortality (43.9% vs. 68.6%,p= 0.004). However, intensified induction regimens with (R)-HDAC were not associated with a real OS benefit in MCL patients undergoing up-front consolidation with ASCT (2-year OS: 88.7% vs. 78.8%,p= 0.289). Up-front ASCT was independently associated with increased OS (p< 0.001), EFS (p= 0.005), and lower POD-24 rates (p< 0.001) in MCL. Additionally, CNS infiltration, TLS, hypoalbuminemia, and the absence of remission after induction were predictors of poor OS. Conclusions: In the largest Latin American cohort of MCL patients, we confirmed the OS benefit promoted by up-front consolidation with ASCT in young and fit patients, regardless of the intensity of the immunochemotherapy regimen used in the pre-ASCT induction. Although HDAC-based regimens were not associated with an unequivocal increase in OS for ASCT-eligible patients, it was associated with higher ORR and lower rates of early relapses for the whole cohort.
背景：套细胞淋巴瘤（MCL）是一种具有异质性的罕见恶性肿瘤。尽管近期治疗取得进展，MCL仍无法治愈。目前，年轻且体能状态良好患者的标准治疗方案包括诱导免疫化疗后进行前期自体干细胞移植（ASCT）。然而，对于适合ASCT的患者，强化诱导方案（如基于大剂量阿糖胞苷的方案）的作用仍存在争议。方法：这项回顾性、观察性、单中心研究纳入了2010年至2022年在拉丁美洲最大肿瘤中心接受治疗的165例MCL患者。我们旨在评估治疗结局、确定生存预测因素，并比较不同初始治疗策略的疗效，重点评估基于HDAC的方案对适合ASCT患者结局的影响。结果：诊断时的中位年龄为65岁（范围38-89岁），73.9%为男性。超过90%的病例为经典淋巴结型（cnMCL），76.4%存在骨髓浸润，56.4%出现脾肿大。分别有32.7%、64.8%、32.1%和95.8%的患者存在≥7 cm大肿块、B症状、ECOG评分≥2和晚期（III/IV期）。64%的患者被归类为高危MIPI。中位随访71.1个月，估计的2年总生存率（OS）和无事件生存率（EFS）分别为64.1%和31.8%。与接受（R）-CHOP方案治疗的患者相比，接受基于（R）-HDAC方案治疗的患者具有更高的总缓解率（ORR）（85.9% vs. 65.7%，p=0.007），以及更低的24个月内疾病进展率（POD-24）（61.9% vs. 80.4%，p=0.043）和更低的死亡率（43.9% vs. 68.6%，p=0.004）。然而，对于接受前期ASCT巩固治疗的MCL患者，（R）-HDAC强化诱导方案并未带来明确的OS获益（2年OS：88.7% vs. 78.8%，p=0.289）。在MCL患者中，前期ASCT与OS延长（p<0.001）、EFS延长（p=0.005）以及更低的POD-24率（p<0.001）独立相关。此外，中枢神经系统浸润、肿瘤溶解综合征、低白蛋白血症以及诱导治疗后未达到缓解是OS不良的预测因素。结论：在这项拉丁美洲最大的MCL患者队列研究中，我们证实了在年轻且体能状态良好的患者中，无论ASCT前诱导阶段使用的免疫化疗方案强度如何，前期ASCT巩固治疗均能带来OS获益。尽管对于适合ASCT的患者，基于HDAC的方案并未明确提高OS，但在整个队列中，该方案与更高的ORR和更低的早期复发率相关。
肿瘤(癌症)患者之家