Tislelizumab Plus HMA and CAG Regimen Shows Improved Response Rates for Relapsed/Refractory AML

The addition of tislelizumab to a hypomethylating agent (HMA) plus cytarabine, aclarubicin/idarubicin, and G-CSF (CAG) regimen demonstrated improved overall response rates and event-free survival in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) compared to historical controls, according to results from a phase 2 study published in Frontiers in Immunology.

Researchers conducted an expanded phase 2 clinical trial (NCT04541277) to determine the efficacy of additional tislelizumab to standard decitabine/azacytidine plus CAG chemotherapy among patients with high-risk R/R AML or AML and aged 60 years or over. In this study, the researchers the sample size, extended the follow-up period, and incorporated new analytical methods, including propensity score matching (PSM), to assess a tislelizumab plus HMA plus CAG regimen for patients with R/R AML.

After propensity score matching (PSM), 37 patients were treated with a combination of tislelizumab, HMA, and CAG and 44 were treated with HMA and CAG chemotherapy. The median age of included patients was 45 years (range, 18 to 71).

The overall response rate (ORR) was higher for patients treated with additional tislelizumab (86.5%) compared to patients treated with HMA and CAG therapy alone (61.4%). More patients in the tislelizumab plus HMA and CAG group achieved complete response (CR; n= 18) then patients in the HMA and CAG group (n= 11).

The overall mortality rate was 54.1% and the overall survival (OS) was 12.1 months (95% confidence interval [CI], 3.7 to 20.5). The median event-free survival (EFS) was 6.2 months (95% CI, 3.1 to 9.3) and the median duration of response [DOR] was also 6.2 months ((95% CI, 3.1 to not reached).

Among patients treated with tislelizumab plus HMA and CAG, 80.7% reported grade 4 thrombocytopenia and 82.5% reported grade 4 neutropenia. Additionally, 77.2% of patients reported grade 3 anemia and 8.5% of patients reported immune-related adverse events grade 2 or 3. No statistical differences were found in adverse event incidences between patients in the tislelizumab plus HMA and CAG group and patients in the HMA and CAG group.

“Overall, the combination regimen improved response rates while maintaining low incidence and severity of immune-related adverse events for R/R AML patients,” the study authors concluded.

“This study provided more comprehensive data for evaluating tislelizumab combined with the tislelizumab + HMA + CAG regimen by increasing the sample size and extending the follow-up time,” they added. “Further confirmation through multicenter exploration and long-term follow-up data is necessary to validate the results of this trial.”  

Source:

Zhou HS, Su YF, Wang J, et al. 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. Frontiers in Immunology. April 16, 2025. doi:10.3389/fimmu.2025.1533467