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Abstract：
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.
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.
摘要：
背景：套细胞淋巴瘤（MCL）是一种罕见的具有异质性行为的恶性肿瘤。尽管最近取得了治疗进展，MCL仍然无法治愈。目前,年轻且健康的患者的标准治疗包括诱导免疫化疗,然后进行前期自体干细胞移植(ASCT).然而,更密集的诱导方案的作用，例如基于高剂量阿糖胞苷（HDAC）的那些，在符合ASCT条件的患者的管理方面仍然存在争议.
方法：本回顾性研究，观察,单中心研究涉及2010年至2022年在拉丁美洲最大的肿瘤中心接受治疗的165名MCL患者。我们旨在评估结果，确定生存预测因子，并比较不同主要治疗策略之间的反应，重点评估基于HDAC的方案对符合ASCT条件的患者结局的影响。
结果：诊断时的中位年龄为65岁（38-89岁），73.9%为男性。超过90％的病例具有经典的结节形式（cnMCL），76.4%有BM入渗，56.4%表现为脾肿大。体积≥7cm,B症状,ECOG≥2，III/IV期晚期占32.7%，64.8%,32.1%,和95.8%，分别。64%的患者被归类为高危MIPI。中位随访时间为71.1个月，估计的两年OS和EFS分别为64.1%和31.8%，分别。以（R）-HDAC为基础的方案治疗的患者ORR较高（85.9％vs.65.7%,p=0.007)与那些接受(R)-CHOP的相比，以及较低的POD-24率（61.9%与80.4%,p=0.043）和较低的死亡率（43.9%与68.6%,p=0.004)。然而,在接受ASCT前期巩固的MCL患者中，（R）-HDAC强化诱导方案与真正的OS益处无关（2年OS：88.7％vs.78.8%,p=0.289）。早期ASCT与OS增加独立相关(p<0.001)，EFS（p=0.005），MCL中POD-24的发生率较低(p<0.001)。此外,CNS浸润,TLS,低蛋白血症,诱导后无缓解是OS差的预测因素。
结论：在拉丁美洲最大的MCL患者队列中，我们证实了在年轻和健康患者中使用ASCT进行前期巩固所促进的OS益处，无论ASCT前诱导中使用的免疫化疗方案的强度如何。尽管基于HDAC的方案与符合ASCT条件的患者的OS明确增加无关，在整个队列中,它与较高的ORR和较低的早期复发率相关.
方法：本回顾性研究，观察,单中心研究涉及2010年至2022年在拉丁美洲最大的肿瘤中心接受治疗的165名MCL患者。我们旨在评估结果，确定生存预测因子，并比较不同主要治疗策略之间的反应，重点评估基于HDAC的方案对符合ASCT条件的患者结局的影响。
结果：诊断时的中位年龄为65岁（38-89岁），73.9%为男性。超过90％的病例具有经典的结节形式（cnMCL），76.4%有BM入渗，56.4%表现为脾肿大。体积≥7cm,B症状,ECOG≥2，III/IV期晚期占32.7%，64.8%,32.1%,和95.8%，分别。64%的患者被归类为高危MIPI。中位随访时间为71.1个月，估计的两年OS和EFS分别为64.1%和31.8%，分别。以（R）-HDAC为基础的方案治疗的患者ORR较高（85.9％vs.65.7%,p=0.007)与那些接受(R)-CHOP的相比，以及较低的POD-24率（61.9%与80.4%,p=0.043）和较低的死亡率（43.9%与68.6%,p=0.004)。然而,在接受ASCT前期巩固的MCL患者中，（R）-HDAC强化诱导方案与真正的OS益处无关（2年OS：88.7％vs.78.8%,p=0.289）。早期ASCT与OS增加独立相关(p<0.001)，EFS（p=0.005），MCL中POD-24的发生率较低(p<0.001)。此外,CNS浸润,TLS,低蛋白血症,诱导后无缓解是OS差的预测因素。
结论：在拉丁美洲最大的MCL患者队列中，我们证实了在年轻和健康患者中使用ASCT进行前期巩固所促进的OS益处，无论ASCT前诱导中使用的免疫化疗方案的强度如何。尽管基于HDAC的方案与符合ASCT条件的患者的OS明确增加无关，在整个队列中,它与较高的ORR和较低的早期复发率相关.
