Mohamed Ahmed, Zabor Emily C, Patel Meera, Zureigat Hadil, Albliwi Moath, Chen Mark Jinan, Nakitandwe Joy, Bosler David S, Kurish Heena, Jain Akriti G, Molina John C, Balderman Sophia, Singh Abhay, Gerds Aaron T, Mukherjee Sudipto, Carraway Hetty E, Advani Anjali S, Mustafa Ali Moaath K
Department of Internal Medicine, Cleveland Clinic, Cleveland, OH.
Department of Quantitative Health Sciences, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
Clin Lymphoma Myeloma Leuk. 2025 Sep;25(9):e668-e674.e9. doi: 10.1016/j.clml.2025.05.012. Epub 2025 May 19.
Survival outcomes of acute lymphoblastic leukemia (ALL) in adults remain inferior to those in the pediatric population. Limited data is present directly comparing different first-line intensive regimens in adult patients with ALL.
We conducted a retrospective study comparing outcomes of first-line intensive chemotherapeutic regimens utilized in adult ALL patients at Cleveland Clinic. Outcomes included composite complete response (CCR), minimal residual disease (MRD) flow cytometry (FC-MRD) response, overall survival (OS) and event-free survival (EFS). Multivariable regression and propensity score (PS) weighting were used for adjustment.
Out of 161 adult patients with ALL between January, 2017 and August, 2023, 100 received an intensive regimen. Of those, 33% (n = 33) received a pediatric-inspired regimen (PIR) (CALGB-10403, n = 32 (97%)), 39% (n = 39) received CALGB-19802, and 28% (n = 28) received Hyper-CVAD. The median age (IQR) was 27 (21-34) for PIR group, 59 (52-65) years for CALGB-19802 group, and 57 (41-66) years for Hyper-CVAD group. The CCR rates were 88%, 82%, and 81% in PIR, CALGB-19802, and Hyper-CVAD groups. The 3-year OS was 78% (95% CI, 63-95), 58% (95% CI, 44-77), and 70% (95% CI, 52-93) (P = .2) in the above groups, respectively. Hyper-CVAD was associated with a higher odds of FC-MRD negative response to CALGB-19802 (PS-adjusted odds ratio: 3.72, 95% CI, 1.05-14.7, P = .041). The 3-year PS-adjusted OS in Hyper-CVAD was 71% (95% CI, 52-97) compared to 49% (95% CI, 33-73) in CALGB-19802 (P = .14).
Compared to an asparaginase-utilizing regimen, CALGB-19802, Hyper-CVAD was associated with higher FC-MRD negative responses. The long-term survival outcomes for patients receiving PIR in young individuals were comparable to those of Hyper-CVAD. Future combination therapies involving blinatumomab and inotuzumab ozogamicin are expected to enhance these outcomes.
成人急性淋巴细胞白血病（ALL）的生存结局仍劣于儿科人群。直接比较成人ALL患者不同一线强化方案的数据有限。
我们进行了一项回顾性研究，比较克利夫兰诊所成人ALL患者使用的一线强化化疗方案的结局。结局包括复合完全缓解（CCR）、微小残留病（MRD）流式细胞术（FC-MRD）反应、总生存（OS）和无事件生存（EFS）。采用多变量回归和倾向评分（PS）加权进行调整。
在2017年1月至2023年8月期间的161例成人ALL患者中，100例接受了强化方案。其中，33%（n = 33）接受了儿科启发方案（PIR）（CALGB-10403，n = 32（97%）），39%（n = 39）接受了CALGB-19802，28%（n = 28）接受了Hyper-CVAD。PIR组的中位年龄（IQR）为27（21 - 34）岁，CALGB-19802组为59（52 - 65）岁，Hyper-CVAD组为57（41 - 66）岁。PIR、CALGB-19802和Hyper-CVAD组的CCR率分别为88%、82%和81%。上述组的3年OS分别为78%（95%CI，63 - 95）、58%（95%CI，44 - 77）和70%（95%CI，52 - 93）（P = 0.2）。与CALGB-19802相比，Hyper-CVAD与FC-MRD阴性反应的较高几率相关（PS调整优势比：3.72，95%CI，1.05 - 14.7，P = 0.041）。Hyper-CVAD的3年PS调整OS为71%（95%CI，52 - 97），而CALGB-19802为49%（95%CI，33 - 73）（P = 0.14）。
与使用天冬酰胺酶的方案CALGB-19802相比，Hyper-CVAD与更高的FC-MRD阴性反应相关。年轻个体接受PIR的长期生存结局与Hyper-CVAD相当。未来涉及博纳吐单抗和奥加伊妥珠单抗的联合疗法有望改善这些结局。
