Study Assesses Clinical Benefit of Immune Checkpoint Inhibitors in MDS

A study presented at the Society of Hematologic Oncology 2024 Annual Meeting in Houston, Texas, investigated the therapeutic benefit associated with immune checkpoint inhibitors (ICIs) for treatment of myelodysplastic syndromes (MDS).

For this study, Vanthana Bharathi, MD, of Saint Peter’s University Hospital in New Brunswick, New Jersey, synthesized data from early-phase clinical trials and ongoing investigations, focusing on ICIs targeting programmed cell death protein 1 (PD-1), programmed death ligand 1 (PD-L1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), and anti-CD47 monoclonal antibodies. Interventions were utilized as monotherapy or in combination with other agents. The analysis included patients with intermediate- to high-risk MDS and patients who demonstrated resistance to hypomethylating agent (HMA) therapy and other standard treatments.

According to the results, PD-1 and PD-L1 inhibitors did not lead to significant clinical results as monotherapy in patients with MDS and acute myeloid leukemia (AML), although they were associated with a relatively favorable safety profile. There were “mixed results” in clinical trials that combined PD-1 and PD-L1 inhibitors with HMAs or chemotherapy, such as “modest improvements in overall response rates but limited overall survival benefits,” Dr. Bharathi wrote. Anti-CD47 therapies also did not lead to significant clinical benefit.

The use of MBG453, a TIM-3 inhibitor, especially combined with HMAs, demonstrated “promising preliminary response rates and antileukemic activity,” Dr. Bharathi noted. Treatment with a CTLA-4 blockade led to disease stabilization in patients with HMA resistance.

“Combination therapies involving PD-1 and CTLA-4 inhibitors exhibit promising activity and tolerability,” Dr. Bharathi summarized, noting that the integration of ICIs into MDS treatment may have potential to advance and personalize therapeutic approaches. “However, larger studies with longer follow-up are needed to fully understand the effectiveness of these regimens and identify biomarkers for response or resistance.”

Reference

Bharathi V. Investigating the therapeutic potential of immune checkpoint inhibitors in myelodysplastic syndromes: a comprehensive review and analysis. Abstract MDS-300. Presented at the Society of Hematologic Oncology 2024 Annual Meeting; September 4-7, 2024; Houston, Texas.