Clinical trials of immune checkpoint inhibitors in acute myeloid leukemia (AML)

Naval G. Daver, MD, from the MD Anderson Cancer Center, Houston, TX, discusses clinical trials of immune checkpoint inhibitors in acute myeloid leukemia (AML) at the International Symposium on Acute Leukemias (ISAL) 2017 in Munich, Germany. He explains the background of this work, which was that in AML patients, high expression of a number of immune checkpoints including PD-1, OX40, and CTLA-4 was seen. A dozen different clinical trials are now assessing different combination approaches with immune checkpoint inhibitors. In AML, the focus has been on the drugs nivolumab and ipilimumab. Dr Daver describes a study of nivolumab in combination with azacytidine, which showed a higher response rate than azacytidine alone, with very durable responses seen in around 35% of patients. In addition, immune profiling at baseline and on treatment showed that patients who responded developed an increasing T-cell infiltrate with response to treatment, with T-cells displaying a favorable immune profile high in CD8 and CD4 effectors. On the other hand, patients who did not respond did not show any favorable T-cell infiltrate in the bone marrow. CTLA-4, an immune checkpoint which can be targeted with ipilimumab, was increased in almost all patients, suggesting that by combinint nivolumab with ipilimumab to block both major immune checkpoints, the response rate may be further increased from 35% to as high as 60 or 80% as has been seen in melanoma. Dr Daver speaks about the next step, which is a frontline treatment with azacitidine in combination with nivolumab, as well as a frontline treatment with the combination of azacitidine, nivolumab and ipilimumab.

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