Dr Komrokji on Ongoing Investigations With Luspatercept in MDS

Rami Komrokji, MD, vice chair, Malignant Hematology Department, head, Leukemia and MDS Section, Moffitt Cancer Center, senior member, Malignant Hematology and Experimental Therapeutics Program, professor, Medicine & Oncologic Sciences, College of Medicine, the University of South Florida, discusses the benefit of agents such as luspatercept-aamt (Reblozyl) in patients with very low– to intermediate-risk myelodysplastic syndromes (MDS) who have not received prior treatment with erythropoiesis-stimulating agents (ESAs).

In August 2023, luspatercept obtained FDA approval for patients with lower-risk MDS with anemia requiring transfusions, he begins. There's a push to consider initiating treatment for patients experiencing symptomatic or significant anemia before the necessity for blood transfusions arises, Komrokji states. The forthcoming phase 3 ELEMENT-MDS study (NCT05949684), which follows the pivotal phase 3 COMMANDS trial (NCT03682536), is specifically designed to investigate this, he says. ELEMENT-MDS intends to focus on patients not in need of blood transfusions and randomly assign them to receive either ESA agents or luspatercept. The goal of the trial is to gather data to support the transition toward treating patients with symptomatic or significant anemia before they require transfusions, Komrokji emphasizes.

Currently, the role of luspatercept in MDS is evolving. Most guidelines suggest its use as a primary treatment option for patients requiring blood transfusions because it has doubled response rates and increased response duration in this subset of patients, Komrokji expands. However, the generalization of these data to patients whose MDS does not have ring sideroblasts (MDS-RS) or is lacking the SF3B1 mutation is debated, he notes. The responses observed with luspatercept in patients without ring sideroblastic disease are similar to those seen with ESA therapies in this population. Yet, specific subsets of patients, especially those anticipated to have a low likelihood of responding to an ESA, may benefit from luspatercept, and the current indication for this agent includes these patients, Komrokji notes.

There's an ongoing effort to explore other disease factors that may favor the use of luspatercept over ESAs, such as baseline mutation burden or specific mutations, he continues. Presently, the consensus is leaning toward using luspatercept as the preferred first-line treatment for all patients with MDS-RS, and as a possible first-line choice for select patients without MDS-RS, Komrokji says. Future research in this area aims to advance treatment strategies so patients can receive therapy before the necessity for blood transfusions, Komrokji concludes.