Venetoclax plus azacitidine and donor lymphocyte infusion in treating acute myeloid leukemia patients who relapse after allogeneic hematopoietic stem cell transplantation

Abstract

This study aimed to evaluate the efficacy and safety of venetoclax plus azacitidine and donor lymphocyte infusion (DLI) in treating patients with relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Twenty-six AML patients who relapsed after allo-HSCT were enrolled and treated with venetoclax plus azacitidine and DLI. Complete remission with incomplete recovery (CRi), partial remission (PR), and objective remission rate (ORR) were assessed, and then event-free survival (EFS) and overall survival (OS) were evaluated. Besides, adverse events were documented. Additionally, whole exome sequencing was performed in bone marrow samples. The CRi, PR, and ORR rates were 26.9%, 34.6%, and 61.5%, respectively. The median time of EFS and OS was 120 (95% CI: 71–610) days and 284.5 (95% CI: 81–610) days, respectively. The most common adverse events were hematologic system adverse events including agranulocytosis, anemia, and thrombocytopenia, while the adverse events of other systems were relatively less and milder. In addition, no serious adverse events existed. Of note, there were 6 (23.1%) patients who developed GVHD. As for gene mutation, 49 mutated genes were found, which were categorized as first-, second-, and third-class mutations, and then further analysis revealed that the first-class mutations were not correlated with EFS or OS. Additionally, the most frequent mutated genes were FLT3, CEBPA, DNMT3A, KIT, KRAS, and NRAS. Venetoclax plus azacitidine and DLI is efficient and tolerant in treating patients with relapsed AML after allo-HSCT, implying this combined therapy as a potential treatment option in the studied patients.

Venetoclax in Relapsed/Refractory Acute Myeloid Leukemia: Are Supporting Evidences Enough?

“…The median duration of response was 7 months (1–11) and median OS was 79 days (2–403), better in responders (403 vs. 55 days, p < 0.0001). A high response rate was 61.5% (including 26.9% of CRi) which has been observed even by Zhao et al [ 77 ] in 26 patients with AML relapsed after allo-HSCT treated with VEN + azacitidine and donor lymphocyte infusion. In the 6 patients relapsed after allogeneic HCT and retrospectively observed by Ram et al [ 85 ], CR/CRi was achieved in 67% of the patients ( n = 4) and the median OS was 12.4 months.…”

Hypomethylating Agent-Based Combination Therapies to Treat Post-Hematopoietic Stem Cell Transplant Relapse of Acute Myeloid Leukemia

“…Lenalidomide (LEN) demonstrates antileukemic activity in patients with PTR; however, it was historically associated with high rates of severe or life-threatening GVHD and was usually contraindicated post-allo-SCT (6,57). Craddock et al conducted a dose-finding study of LEN administered in combination with AZA in patients with PTR of AML (n = 24) and MDS (n = 5).…”

“…After relapse, 3-year survival is particularly poor, with less than 20% of patients surviving and not exceeding 4% after early relapse (<6 months) (2)(3)(4)(5). Patients who received a reduced-intensity conditioning regimen, who never had graft-versus-host disease (GVHD), who lost donor chimerism, and who have a measurable residual disease (MRD) have a higher risk of relapse (1,6,7).…”

Prevention and Treatment of Acute Myeloid Leukemia Relapse after Hematopoietic Stem Cell Transplantation: The State of the Art and Future Perspectives

“…The median number of cycles to achieve the remission was two (1–2). Median EFS and OS were, respectively, 120 days and 284 days [ 90 ].…”

“…Indeed, the combination of venetoclax with azacytidine and DLI, in this setting of patients, induced 26.9% of CRi and 34.6% of PR. Looking at the event-free survival (EFS) and OS they were 120 and 284.5 days respectively [ 90 ].…”