Department of Haematology, Oxford University Hospital NHS Foundation Trust, Oxford, UK.
Oxford University Graduate Academic School, Oxford, UK.
Br J Haematol. 2021 Jul;194(2):365-377. doi: 10.1111/bjh.17513. Epub 2021 May 7.
Mantle cell lymphoma (MCL) presenting in elderly, unfit patients represents a clinical challenge. Front-line 'attenuated' or low-intensity immunochemotherapy is often employed, although outcomes are relatively unexplored. We report outcomes of attenuated immunochemotherapy in 95 patients with MCL across 19 centres in the UK and Ireland considered unfit for full-dose rituximab-bendamustine or rituximab-cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP). Regimens examined were rituximab-cyclophosphamide, vincristine, prednisolone (R-CVP) (n = 19), dose-attenuated R-CHOP (n = 22), dose attenuated rituximab-bendamustine (n = 24) and rituximab-chlorambucil (n = 30). The primary outcome was progression-free survival (PFS). The secondary outcomes included overall response, overall survival (OS) and toxicity. The median (range) age was 79 (58-89) years and 50% were aged ≥80 years. The median (range) Cumulative Illness Rating Scale-Geriatric score was 6 (0-24). The median PFS for all patients was 15 months [95% confidence interval (CI) 8·7-21·2) and median OS was 31·4 months (95% CI 19·7-43·2). By multivariable analysis (MVA), the only clinical factor associated with an inferior PFS was blastoid morphology [hazard ratio (HR) 2·90, P = 0·01). Notably, higher treatment intensity (R-CHOP/R-bendamustine composite) provided an independently superior PFS compared with R-CVP/R-chlorambucil (MVA HR 0·49, P = 0·02). Factors associated with inferior OS by MVA were Eastern Cooperative Oncology Group Performance Status (HR 2·14, P = 0·04), blastoid morphology (HR 4·08, P = 0·001) and progression of disease at <24 months status (HR 5·68, P < 0·001). Overall, survival after front-line dose-attenuated immunochemotherapy is unsatisfactory. Clinical trials investigating novel agents such as Bruton tyrosine kinase and B-cell lymphoma 2 inhibitors in this specific clinical setting are warranted.
套细胞淋巴瘤（MCL）在老年、不适宜患者中表现出临床挑战。一线“减轻”或低强度免疫化疗通常被采用，尽管其结果尚不清楚。我们报告了在英国和爱尔兰的 19 个中心中，95 名不适合接受全剂量利妥昔单抗-苯达莫司汀或利妥昔单抗-环磷酰胺、多柔比星、长春新碱、泼尼松（R-CHOP）治疗的 MCL 患者接受免疫化疗的结果。检查的方案为利妥昔单抗-环磷酰胺、长春新碱、泼尼松（R-CVP）（n=19）、剂量减弱的 R-CHOP（n=22）、剂量减弱的利妥昔单抗-苯达莫司汀（n=24）和利妥昔单抗-苯丁酸氮芥（n=30）。主要结局是无进展生存期（PFS）。次要结局包括总反应、总生存期（OS）和毒性。患者的中位（范围）年龄为 79（58-89）岁，50%的患者年龄≥80 岁。累积疾病严重程度评分-老年评分的中位数（范围）为 6（0-24）。所有患者的中位 PFS 为 15 个月[95%置信区间（CI）为 8.7-21.2]，中位 OS 为 31.4 个月（95%CI 为 19.7-43.2）。通过多变量分析（MVA），唯一与较差 PFS 相关的临床因素是母细胞样形态[风险比（HR）2.90，P=0.01]。值得注意的是，较高的治疗强度（R-CHOP/R-苯达莫司汀组合）与 R-CVP/R-苯丁酸氮芥相比，提供了独立的更优 PFS（MVA HR 0.49，P=0.02）。通过 MVA 与较差 OS 相关的因素包括东部肿瘤协作组表现状态（HR 2.14，P=0.04）、母细胞样形态（HR 4.08，P=0.001）和疾病进展<24 个月的状态（HR 5.68，P<0.001）。总体而言，一线剂量减弱免疫化疗后的生存情况并不令人满意。有必要在这一特定临床环境中开展临床试验，以研究布鲁顿酪氨酸激酶和 B 细胞淋巴瘤 2 抑制剂等新型药物。
