Combination of CCAG Regimen and Donor Lymphocyte Infusion Induced Durable Remission and Superior Survival Among Patients With Relapsed AML/MDS

Results from a Phase 2 Single-Arm Clinical Trial

The use of chidamine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor (CCAG) followed by donor lymphocyte infusion (DLI) treatment resulted in improved durable remission and superior survival rates among patients with relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who previously underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), according to a phase 2 study published in Medical Oncology. 

“Chemotherapy in combination with donor lymphocyte infusion is a standard treatment for relapsed AML/myelodysplastic syndrome after allo-HSCT. Unfortunately, the therapy induces remission in less than 40% of patients. Besides, pancytopenia, infection, and graft-versus-host disease (GVHD) frequently occur in patients, leading to poor outcomes,” Yan Wei, MD, Chinese PLA General Hospital, Beijing, China, and coauthors stated as the impetus for this study. 

This phase 2 single-arm clinical trial enrolled a total of 20 patients with relapsed AML (90% of patients) or MDS (10% of patients) after allo-HSCT treatment, with a median age of 47.5 years (ranging 21 to 60 years). 35% of patients were categorized as intermediate risk, 60% as poor risk, and 5% as very poor risk, according to the National Comprehensive Cancer Network (NCCN). 

Patients received a CCAG and DLI regimen every 30 to 45 days (30 mg chidamide on days 1, 4, 8, and 11; 10 mg/m2 cytarabine every 12 hours from days 1 to 5 for positive minimal residual disease [MRD+] patients and 100 mg every 12 hours from days 1 to 5 for patients with hematologic relapse; 20 mg aclarubicin on days 1, 3, and 5, 300 µg G-CSF from day 0 until neutrophils ≥ 2×109/L was achieved; and DLI performed on day 7). Treatment was to continue until negative MRD was observed, and was to be administered at a maximum of 3 consecutive cycles. Treatment was to be discontinued in the case of disease progression, unacceptance toxicities, or withdrawal of consent. 

Among all enrolled patients who received treatment, 9 (45%) achieved complete remission (CR) after 1 round and had negative MRD when they completed treatment. 1 patient achieved partial remission (PR) but ended up withdrawing from the study. After 1 year, the overall survival (OS) rate was 56.7% (95% confidence interval [CI]), with a median OS of 19 months. The 1-year relapse-free survival (RFS) rate was 83.3% (95% CI). Of the other patients who did not achieve CR/PR after CCAG and DLI therapy, 5 patients received other treatments but never achieved CR, 3 patients withdrew from further treatment, and 2 had rapidly progressive disease. 

An assessment of toxicity and graft versus host disease (GVHD) found that cumulative incidence of grade 2 to 4 acute GVHD was 33.5%, with only 9.4% of patients having grade 3 to 4 acute GVHD, and none of which were associated with risk factors. Chronic GVHD was observed in 4 patients (20%), most of whom had mild-moderate involvement and all of whom were in a stable condition. The most common adverse events were hematological, including anemia, leukopenia, and neutropenia, and were mostly reversible after CCAG regimen was terminated. 

As primary endpoints were met, Dr. Wei et al concluded, “CCAG plus DLI regimen was feasible and effective in relapsed AML/MDS patients after allo-HSCT, especially in patients with a relatively long post-HSCT remission duration,” adding, “a study with a larger cohort is needed to verify the results.” 

Source: 

Wei Y, Wang L, Zhu C, et al. A phase II study of chidamide, cytarabine, aclarubicin, granulocyte colony-stimulating factor, and donor lymphocyte infusion for relapsed acute myeloid leukemia and myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation. Med Oncol. 2023;40(2):77. Published 2023 Jan 10. doi:10.1007/s12032-022-01911-9