Nonablative chemotherapy followed by HLA-mismatched allogeneic T-cell infusion (allo-TLI) appears to be safe and efficacious in older patients with acute myeloid leukemia (AML) or intermediate-2 to high-risk myelodysplastic syndrome (MDS), according to research published in Frontiers in Oncology.
“[Older patients with AML and intermediate-2 to high-risk MDS] are usually insensitive to or cannot tolerate regular chemotherapies, and may not have the opportunity to undergo allogeneic stem cell transplantation,” the investigators wrote in their report.
The team conducted a prospective, multicenter, single-arm clinical trial to evaluate the efficacy and safety of standard or low-dose chemotherapy followed by allo-TLI for the treatment of older patients with AML or intermediate-2 to high-risk MDS (China Clinical Trials Registry: ChiCTR-ONC-17011948).
A total of 25 patients (17 AML and 8 MDS), with a median age of 65 years (interquartile range [IQR], 62-68), were enrolled in the study at 3 hospitals between 2017 and 2020. Of the patients with AML, 53% were considered high-risk, and of those with MDS, 62% were considered intermediate-2 while 38% were considered high risk.
Patients were administered 4 courses of non-ablative chemotherapy (AML: decitabine, idarubicin, and cytarabine; MDS: decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor) with HLA-mismatched donor CD3+ allo-TLI 24 hours after each course. Overall, 79 procedures were performed. Of the patient/donor pairs, 64% were matched at fewer than 5 of 10 HLA alleles. The median follow-up duration was 30.0 months (range, 1.2–35.9 months).
The investigators compared patient outcomes to a historical control cohort comprising 30 older patients (median age, 66 years; IQR, 63-70) with AML treated with idarubicin plus cytarabine (3 + 7) at First Affiliated Hospital, Zhejiang University School of Medicine in Hangzhou, China, between 2010 and 2016. The median follow-up duration was 61.2 months (range, 0.2-62.2 months).
Patients with AML and MDS who were treated with nonablative chemotherapy and allo-TLI had overall response rates of 94% and 75%, respectively, and had 1-year overall survival (OS) rates of 88% and 60%, respectively. Overall, the 60-day treatment-related mortality rate was 8%.
When compared with the historical control cohort treated with idarubicin plus cytarabine, the patients treated with nonablative chemotherapy and allo-TLI showed significantly higher overall response (94% vs 50%; P =.002) and 1-years OS rates (88% vs 27%; P =.014).
Following allo-TLI, cytokine-release syndrome (CRS) occurred in 79% of procedures; most (96%) CRS reactions were grade 1. There was 1 death due to grade 5 acute graft vs host disease.
“Our study showed that nonablative chemotherapy followed by HLA-mismatched allo-TLI is safe and effective, and may thus be used as a first-line treatment for these patients,” the investigators concluded in their report. “Post-TLI CRS is common and usually mild, and a higher T-cell level after allo-TLI may be related to better blood cell recovery, while more cycles of HLA-mismatched allo-TLI may increase recipients’ T-cell levels, contributing to improved survival.”
Huang Y, Hong M, Qu Z, et al. Non-ablative chemotherapy followed by HLA-mismatched allogeneic CD3+ T-cells infusion causes an augment of T-cells with mild CRS: a multi-centers single-arm prospective study on elderly acute myeloid leukemia and int-2/high risk myelodysplastic syndrome patients. Front Oncol. 2021;11:741341. doi:10.3389/fonc.2021.741341