Tun Aung M, Wang Yucai, Maliske Seth, Micallef Ivana, Inwards David J, Habermann Thomas M, Porrata Luis, Paludo Jonas, Bisneto Jose Villasboas, Rosenthal Allison, Kharfan-Dabaja Mohamed A, Ansell Stephen M, Nowakowski Grzegorz S, Farooq Umar, Johnston Patrick B
Division of Hematology, Mayo Clinic, Rochester, Minnesota; Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas, Kansas City, Kansas.
Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Transplant Cell Ther. 2024 Oct;30(10):1001.e1-1001.e12. doi: 10.1016/j.jtct.2024.07.008. Epub 2024 Jul 10.
The standard of care (SOC) for fit patients with relapsed diffuse large B-cell lymphoma (DLBCL) ≥12 months after completing frontline therapy is salvage chemotherapy (ST) followed by autologous stem cell transplant (ASCT). However, this strategy may not be optimal for patients with certain clinical characteristics. We retrospectively studied 151 patients with DLBCL that relapsed ≥12 months after R-CHOP or R-CHOP-like frontline therapy who underwent ST and ASCT at Mayo Clinic between July 2000 and December 2017 or the University of Iowa between April 2003 and April 2020. Clinical characteristics, treatment information, and outcome data were abstracted. Progression-free survival (PFS) and overall survival (OS) from the time of ASCT were analyzed using the Kaplan-Meier method. The median time from frontline therapy completion to 1st relapse was 26.9 months. The median line of ST was 1 (range 1-3), and 17 (11%) patients required >1 line of ST. Best response before ASCT was partial response (PR) in 60 (40%) and complete response (CR) in 91 (60%) patients. The median age at ASCT was 64 yr (range 19-78), and 36 (24%) patients were of ≥70 yr. The median follow-up after ASCT was 87.3 months. The median PFS and OS were 54.5 and 88.9 months, respectively. There was no significant difference in PFS and OS based on the age at ASCT (including patients aged ≥70-78 yr), sex, transplant era, time to relapse, LDH, extranodal site involvement, and central nervous system/nerve involvement at relapse. However, patients with advanced-stage relapse had inferior PFS than those with early-stage relapse (median 45.3 versus 124.7 months, P = .045). Patients who required > 1 line of ST, compared to those requiring 1 line, had significantly inferior PFS (median 6.1 versus 61.4 months, P < .0001) and OS (17.8 versus 111.7 months, P = .0004). There was no statistically significant difference in survival in patients who achieved PR versus CR, though numerically inferior in the former, with median PFS of 38.9 versus 59.3 months (P = .23) and median OS of 78.3 versus 111.7 months (P = .62). Patients achieving CR after 1 line of ST had excellent post-ASCT outcomes, with median PFS of 63.7 months. In conclusion, survival after ASCT was unfavorable in patients with late relapsed DLBCL (≥12 months) who required more than 1 line of ST to achieve PR or CR, and such patients should be treated with alternative therapies. Conversely, survival was favorable in patients who required only 1 line of ST, supporting the current clinical practice of ASCT consolidation in these patients. Moreover, outcomes were favorable in patients aged ≥70 to 78 yr at ASCT, similar to younger patients, highlighting the safety and feasibility of this approach in such patients.
对于完成一线治疗后≥12个月复发的适合的弥漫性大B细胞淋巴瘤(DLBCL)患者,标准治疗(SOC)是挽救性化疗(ST),随后进行自体干细胞移植(ASCT)。然而,对于具有某些临床特征的患者,这种策略可能并非最佳选择。我们回顾性研究了151例在2000年7月至2017年12月于梅奥诊所或2003年4月至2020年4月于爱荷华大学接受ST和ASCT的、在R-CHOP或类似R-CHOP一线治疗后≥12个月复发的DLBCL患者。提取了临床特征、治疗信息和结局数据。采用Kaplan-Meier方法分析自ASCT时间起的无进展生存期(PFS)和总生存期(OS)。从一线治疗完成到首次复发的中位时间为26.9个月。ST的中位疗程为1(范围1 - 3),17例(11%)患者需要>1疗程的ST。ASCT前的最佳缓解为部分缓解(PR)的有60例(40%),完全缓解(CR)的有91例(60%)。ASCT时的中位年龄为64岁(范围19 - 78岁),36例(24%)患者年龄≥70岁。ASCT后的中位随访时间为87.3个月。中位PFS和OS分别为54.5个月和88.9个月。基于ASCT时的年龄(包括年龄≥70 - 78岁的患者)、性别、移植时代、复发时间、乳酸脱氢酶(LDH)、结外部位受累情况以及复发时中枢神经系统/神经受累情况,PFS和OS无显著差异。然而,晚期复发患者的PFS低于早期复发患者(中位45.3个月对124.7个月,P = 0.045)。与需要1疗程ST的患者相比,需要>1疗程ST的患者的PFS(中位6.1个月对61.4个月,P < 0.0001)和OS(17.8个月对111.7个月,P = 0.0004)显著更差。达到PR与CR的患者在生存方面无统计学显著差异,尽管前者在数值上较差,PR患者的中位PFS为38.9个月对59.3个月(P = 0.23),中位OS为78.3个月对111.7个月(P = 0.62)。经过1疗程ST后达到CR的患者在ASCT后的结局良好,中位PFS为63.7个月。总之,对于晚期复发(≥12个月)的DLBCL患者,若需要超过1疗程的ST才能达到PR或CR,ASCT后的生存情况不佳,此类患者应采用替代疗法治疗。相反,仅需要1疗程ST的患者生存情况良好,支持当前对这些患者进行ASCT巩固治疗的临床实践。此外,ASCT时年龄≥70至78岁的患者结局良好,与年轻患者相似,突出了这种方法在此类患者中的安全性和可行性。