Dr Zeidan on the Evaluation of Immunotherapy and Other Novel Therapies in MDS

“I’m quite excited about several of these agents, and hopefully we get to report on the results from the trials [evaluating them] in the near future.”

Amer Zeidan, MBBS, director of Early Therapeutics Research, director of the Leukemia and Myeloid Malignancies Program, assistant medical director of the Clinical Trials Office, and co-leader of the Leukemia and Myeloid Malignancies Clinical Research Team at Yale Cancer Center; as well as chief of the Division of Hematologic Malignancies and a professor of internal medicine (hematology) at Yale School of Medicine, discussed ongoing and recently completed clinical trials evaluating immunotherapy and other novel agents in patients with myelodysplastic syndromes (MDS).

A phase 1 clinical trial (NCT02117219) evaluated durvalumab (Imfinzi), a PD-L1 immune checkpoint inhibitor, in patients with MDS. Unfortunately, the study failed to demonstrate meaningful therapeutic benefit with durvalumab in this patient population, Zeidan said.

Another agent of interest is the TIM-3 inhibitor sabatolimab (MBG453), which was evaluated in treatment-naive patients with higher-risk MDS in the randomized phase 2 STIMULUS-MDS1 trial (NCT03946670). Data published in Lancet Hematology showed that the combination of sabatolimab plus hypomethylating agents produced early signals of efficacy, includingpotentially durable responses, though it failed to significantly improve progression-free survival or complete response rates, according to Zeidan. Subsequently, the phase 3 STIMULUS-MDS2 trial (NCT04266301), data from which were presented at the 2024 EHA Congress, assessed sabatolimab plus azacitidine (Vidaza) vs azacitidine plus placebo in 530 patients with first-line higher-risk MDS or chronic myelomonocytic leukemia. This trial showed a numerical though not statistically significant increase in overall survival with the investigational combination vs azacitidine plus placebo, Zeidan noted.

Ongoing trials of interest in this field include the phase 3 VERONA study (NCT04401748) investigating azacitidine plus venetoclax (Venclexta) vs azacitidine plus placebo in patients with newly diagnosed, higher-risk MDS. Additionally, the phase 3 ELEMENT-MDS trial (NCT05949684) is evaluating luspatercept-aamt (Reblozyl) in patients who are transfusion independent but remain anemic. Additional early-phase research includes development of the pyruvate kinase activator tebipivat (AG-946) for patients with lower-risk MDS with anemia; as well as the immune checkpoint inhibitors AK117 and bexmarilimab, which target CD47 and Clever-1, respectively, in patients with high-risk MDS, he concluded.