Division of Hematology, Mayo Clinic, Rochester, Minnesota; Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas, Kansas City, Kansas.
Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, Iowa.
Transplant Cell Ther. 2022 Sep;28(9):610-617. doi: 10.1016/j.jtct.2022.06.015. Epub 2022 Jun 22.
Patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who achieve progression-free survival (PFS) at 24 months (PFS24) after immunochemotherapy (IC) have excellent overall survival (OS) comparable to that of the age- and sex-matched general population. However, a similar landmark has not been established for patients with relapsed or refractory (RR) DLBCL following frontline IC who are subsequently treated with salvage therapy followed by autologous stem cell transplantation (ASCT). To evaluate the role of PFS24 as a landmark after ASCT in patients with RR DLBCL, we identified patients with RR DLBCL after frontline R-CHOP or R-CHOP-like IC who underwent salvage therapy and ASCT at Mayo Clinic between July 2000 and December 2017 and University of Iowa between April 2003 and April 2020 from institutional lymphoma and transplantation databases. Clinical characteristics, treatment information, and outcome data were abstracted. PFS, OS, and post-ASCT relapse survival (PRS) were analyzed using Kaplan-Meier method, and cumulative incidences of relapse versus nonrelapse mortality and different causes of death were compared accounting for competing events. A total of 437 patients were identified. Median age at ASCT was 61 years (range 19-78), and 280 (64%) were male. After a median post-ASCT follow-up of 8.0 years (95% confidence interval [CI], 7.2-8.7), 215 patients had a relapse (or disease progression), 180 within 2 years and 35 after 2 years. For the entire cohort, the post-ASCT relapse rate was much higher than the nonrelapse mortality rate (48.1% versus 9.1% at 5 years). Median PFS and OS after ASCT was 2.7 and 5.4 years, respectively. Lymphoma was the primary cause of death after ASCT. In contrast, for patients who had achieved PFS24 (n = 220), rates of post-PFS24 relapse and nonrelapse mortality were similar (14.8% and 12.3% at 5 years). Median PFS and OS after achieving PFS24 was 10.0 and 11.5 years, respectively. Lymphoma-related and -unrelated death rates were similar after achieving PFS24. For all patients who had a post-ASCT relapse, median PRS was 0.7 (95% CI, 0.5-0.9) year, and late relapse (>2 versus ≤2 years after ASCT) was associated with better PRS (median 2.3 [1.7-4.8] versus 0.5 [0.3-0.7] years, P< .001). The study establishes PFS24 as an important landmark associated with post-ASCT outcomes in patients with RR DLBCL after frontline IC.
新诊断为弥漫性大 B 细胞淋巴瘤(DLBCL)的患者,在免疫化疗(IC)后 24 个月时达到无进展生存期(PFS)(PFS24),其总生存期(OS)与年龄和性别匹配的一般人群相当。然而,对于一线 IC 后复发或难治(RR)DLBCL 患者,在接受挽救性治疗和自体干细胞移植(ASCT)后,尚未建立类似的里程碑。为了评估 PFS24 在 RR DLBCL 患者 ASCT 后的标志作用,我们从机构淋巴瘤和移植数据库中确定了在 2000 年 7 月至 2017 年 12 月期间在梅奥诊所和 2003 年 4 月至 2020 年 4 月期间在爱荷华大学接受一线 R-CHOP 或 R-CHOP 样 IC 治疗后发生 RR DLBCL 且随后接受挽救性治疗和 ASCT 的患者。提取临床特征、治疗信息和结果数据。使用 Kaplan-Meier 方法分析 PFS、OS 和 ASCT 后复发存活(PRS),并比较复发与非复发死亡率以及不同原因死亡的累积发生率,同时考虑竞争事件。共确定了 437 例患者。ASCT 时的中位年龄为 61 岁(范围 19-78),280 例(64%)为男性。ASCT 后中位随访 8.0 年(95%置信区间[CI],7.2-8.7),215 例患者发生复发(或疾病进展),其中 180 例在 2 年内,35 例在 2 年后。对于整个队列,ASCT 后复发率明显高于非复发死亡率(5 年时分别为 48.1%和 9.1%)。ASCT 后的中位 PFS 和 OS 分别为 2.7 年和 5.4 年。淋巴瘤是 ASCT 后死亡的主要原因。相比之下,对于那些达到 PFS24 的患者(n=220),在达到 PFS24 后发生复发和非复发死亡率的比例相似(5 年时分别为 14.8%和 12.3%)。达到 PFS24 后,中位 PFS 和 OS 分别为 10.0 年和 11.5 年。达到 PFS24 后,淋巴瘤相关和非相关死亡率相似。对于所有发生 ASCT 后复发的患者,中位 PRS 为 0.7 年(95%CI,0.5-0.9),晚期复发(>2 年与≤2 年 ASCT)与更好的 PRS 相关(中位值 2.3 [1.7-4.8]与 0.5 [0.3-0.7]年,P<0.001)。该研究确立了 PFS24 是一线 IC 后 RR DLBCL 患者 ASCT 后预后的重要标志。