Background: Diffuse large B-cell lymphoma (DLBCL) especially affects the older population. Old (≥60 years) and very old age (≥80 years) DLBCL patients often present high-risk molecular alterations, lower tolerability to conventional immunochemotherapy, and poor clinical outcomes. In this scenario, attenuated therapeutic strategies, such as the R-MiniCHOP and R-MiniCHOP of the elderly regimens, have emerged for this particularly fragile population. However, the responses, clinical outcomes, and toxicities of these regimens currently remain poorly understood, mainly because these individuals are not usually included in controlled clinical trials. Methods: This retrospective, observational, and single-center real-world study included 185 DLBCL, NOS patients older than 70 years treated at the largest oncology center in Latin America from 2009 to 2020. We aimed to assess the outcomes, determine survival predictors, and compare responses and toxicities between three different primary therapeutic strategies, including the conventional R-CHOP regimen and the attenuated R-MiniCHOP and R-MiniCHOP of the elderly protocols. Results: The median age at diagnosis was 75 years (70–97 years), and 58.9% were female. Comorbidities were prevalent, including 19.5% with immobility, 28.1% with malnutrition, and 24.8% with polypharmacy. Advanced clinical stage was observed in 72.4%, 48.6% had bulky disease ≥7 cm, 63.2% had B-symptoms, and 67.0% presented intermediate–high/high-risk IPI. With a median follow-up of 6.3 years, the estimated 5-year OS and PFS were 50.2% and 44.6%, respectively. The R-MiniCHOP of the elderly regimen had a lower ORR (p= 0.040); however, patients in this group had higher rates of unfavorable clinical and laboratory findings, including hypoalbuminemia (p= 0.001), IPI ≥ 3 (p= 0.013), and NCCN-IPI ≥ 3 (p= 0.002). Although associated with higher rates of severe neutropenia (p= 0.003), the R-CHOP regimen promoted increased OS (p= 0.003) and PFS (p= 0.005) in comparison to the attenuated protocols. Additionally, age ≥ 75 years, high levels of LDH, B-symptoms, advanced clinical stage (III/IV), neutrophilia, and low lymphocyte/monocyte ratio were identified as poor prognostic factors in this cohort. Conclusions: In this large and real-life Latin American cohort, we demonstrated that patients with DLBCL, NOS older than 70 years still do not have satisfactory clinical outcomes in 2024, with half of cases not reaching 5 years of life expectancy after diagnosis. Although the conventional R-CHOP offers response and survival advantages over attenuated regimens, its myelotoxicity is not negligible. Therefore, the outcomes reported and the prognostic factors here identified may assist clinicians in the appropriate selection of therapeutic strategies adapted to the risk for old and very old DLBCL patients.
背景：弥漫性大B细胞淋巴瘤（DLBCL）尤其影响老年人群。老年（≥60岁）及高龄（≥80岁）DLBCL患者常伴有高风险分子学改变、对常规免疫化疗耐受性较低且临床预后较差。在此背景下，针对这一特殊脆弱人群出现了减量化治疗策略，如R-MiniCHOP方案及老年版R-MiniCHOP方案。然而，目前对这些方案的治疗反应、临床结局及毒性特征仍知之甚少，主要因为这类患者通常未被纳入对照临床试验。 方法：这项回顾性、观察性、单中心真实世界研究纳入了2009年至2020年在拉丁美洲最大肿瘤中心接受治疗的185例70岁以上DLBCL非特指型患者。我们旨在评估治疗结局，确定生存预测因素，并比较三种不同一线治疗策略（包括常规R-CHOP方案、减量R-MiniCHOP方案及老年版R-MiniCHOP方案）的治疗反应和毒性差异。 结果：诊断中位年龄为75岁（范围70-97岁），58.9%为女性。合并症普遍存在，其中19.5%存在活动受限，28.1%存在营养不良，24.8%存在多重用药。72.4%的患者处于晚期临床分期，48.6%有大肿块（≥7 cm），63.2%伴有B症状，67.0%具有中高危/高危国际预后指数（IPI）。中位随访6.3年，预估5年总生存率（OS）和无进展生存率（PFS）分别为50.2%和44.6%。老年版R-MiniCHOP方案的总缓解率（ORR）较低（p=0.040），但该组患者具有更多不良临床和实验室特征，包括低白蛋白血症（p=0.001）、IPI≥3（p=0.013）及NCCN-IPI≥3（p=0.002）。尽管R-CHOP方案与较高的重度中性粒细胞减少发生率相关（p=0.003），但与减量方案相比，其显著提升了OS（p=0.003）和PFS（p=0.005）。此外，年龄≥75岁、高水平乳酸脱氢酶（LDH）、B症状、晚期临床分期（III/IV）、中性粒细胞增多及低淋巴细胞/单核细胞比值被确定为该队列的不良预后因素。 结论：在这项大型拉丁美洲真实世界队列研究中，我们证实截至2024年，70岁以上DLBCL非特指型患者的临床结局仍不理想，半数病例在诊断后未能达到5年预期生存期。虽然常规R-CHOP方案相较于减量方案在治疗反应和生存方面具有优势，但其骨髓毒性不容忽视。因此，本研究报告的治疗结局及确定的预后因素，可协助临床医生根据老年及高龄DLBCL患者的风险特征，选择适宜的治疗策略。
肿瘤(癌症)患者之家