Updates from a single-center phase 2 study of PD-1 inhibitor combined with hypomethylating agent plus CAG regimen in patients with relapsed/refractory acute myeloid leukemia

TL;DR

This study shows that combining a PD-1 inhibitor with other drugs improves outcomes for patients with relapsed or refractory acute myeloid leukemia.

Contribution

The study introduces a combination therapy with a PD-1 inhibitor that shows improved response rates and survival in r/r AML patients.

Findings

The overall response rate was 69.4% with a median overall survival of 12.1 months.

Patients aged 40 or older had a higher response rate, and those with lower leukemia burden had better survival outcomes.

Adding tislelizumab improved response rates and event-free survival compared to historical controls.

Abstract

Anti-PD-1 monotherapy has shown limited clinical efficacy in patients with relapsed/refractory acute myeloid leukemia (r/r AML). Our study aimed to analyze the effectiveness and safety of combining tislelizumab with a hypomethylating agent (HMA) plus CAG regimen in treating patients with r/r AML, with an increased sample size and in comparison, with a historical control group for more reliable data support (ClinicalTrials.gov identifier NCT04541277).

The study included a total of 37 patients with r/r AML who received the tislelizumab + HMA + CAG regimen.

The overall response rate was 69.4%, with a median overall survival of 12.1 months and event-free survival of 6.2 months. Multivariate analysis revealed that patients aged 40 or above exhibited a higher response rate, while those with lower leukemia burden (bone marrow blast percentage <40%) demonstrated improved overall survival and event-free survival. Additionally, bridging allogeneic hematopoietic stem cell transplantation was associated with extended event-free survival. Grade 2-3 immune-related adverse events were observed in 8.5% of patients, and no deaths were directly attributed to these events. After propensity score matching, the inclusion of tislelizumab appeared to positively influence the overall response rate and event-free survival compared to historical controls treated with HMA + CAG regimen.

Overall, the combination regimen improved response rates while maintaining low incidence and severity of immune-related adverse events for r/r AML patients.

https://clinicaltrials.gov/, identifier NCT04541277.

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