Guillermo Garcia-Manero, MD, MD Anderson Cancer Center, Houston, Texas, reviewed the various treatment options available and upcoming for patients with low-risk myelodysplastic syndrome (MDS).

This research was presented at the 2024 Annual Society of Hematologic Oncology (SOHO) meeting in Houston, Texas.

Transcript:

Good morning. My name is Guillermo Garcia-Manero from the Department of Leukemia at MD Anderson Cancer Center in Houston, Texas. I'm going to give you a summary of what we presented at the annual meeting of the Society of Hematology Oncology (SOHO) during the first week of September 2024 here in Houston.

I had the honor to serve the society at the meeting as president of SOHO, and therefore helping organize the meeting. That was a great privilege, and this was a very successful meeting with colleagues and partners from all over the world coming to Houston to discuss recent progress in different types of hematological malignancies.

I'm going to summarize some of our data presented or presentations around progress in myelodysplastic syndromes (MDS) [treatment]. As the audience knows, myelodysplastic syndromes are a quite heterogeneous group of myeloid disorders. Some of these conditions have a very benign prognosis. Some of them are more complex situations associated with poor prognosis. Over the last few years, we've been able to incorporate molecular data to classify our patients. For instance, using the Molecular International Prognostic Scoring System (IPSSM) tool and using either this or the Revised IPSS (IPSS-R), we divide patients into what we call lower-risk and higher-risk. Then we try to adapt therapeutics based on the predicted natural history for these patients and in lower-risk disease.

Although I think the goal should be to cure these patients, we're focusing on improving cytopenia and minimizing transfusion needs. Over the last 2 or 3 years, we've seen significant progress in the treatment of these patients with lower-risk MDS. We saw interesting data from a European group, led by the Spanish MDS group, indicating that early intervention with low-dose lenalidomide in transmission independent patients with deletion 5Q- disease is associated with a long period of transmission-free interval, as compared to those patients [treated with] the standard of care waited for them to become transmission-dependent.

What is very interesting from this data is that the rate of cytogenetic complete responses in those patients treated with low-dose lenalidomide early in the course of the disease is significantly higher than what you see once these patients have a little bit more progressive disease with more anemia and transfusion needs. It is possible that this kind of intervention may improve the survival of these patients. Of course, we need to see this data probably a few years from now.

The second issue that was quite important was the development of luspatercept. This is the TGF-β inhibitor first approved after the phase 3 MEDALIST trial around 2020 for second line [treatment] for patients with ring sideroblastic anemia. This was followed by a study known as the COMMANDS trial that was presented in 2023 at multiple meetings. The study allowed for the approval of luspatercept in [the] first line [setting] for patients with low-risk MDS [who were] transfusion dependent in terms of red [blood] cells.

This is a very important study, randomizing again, luspatercept versus epoetin alfa. On an intent-to-treat analysis, the study was superior to the standard of care in terms of both the rates of transfusion dependency and the increase in hemoglobin levels. That was the dual primary end point of the COMMANDS trial. What is more important for me is that the duration of response with luspatercept upfront was significantly longer also than what we saw with the epoetin-stimulating agent, indicating that not only you have a greater rate of response, but a better quality of dose responses.

Now we have luspatercept in the first-line for all [ ] low-risk MDS and in second-line for patients with ring sideroblastic anemia. This was followed by another study called the IMerge study, where an agent that modulates the telomerase activity in second-line in a design similar to the MEDALIST trial, [has] shown significant activity in patients with transfusion dependent low risk MDS that have already received 1 agent or are not candidates for an erythropoiesis stimulating agent (ESA) because maybe their [epoetin] level is high.

We have quite a robust portfolio of drugs for anemia in low-risk MDS: luspatercept, imetelstat, early intervention with lenalidomide, and of course we still have the hypomethylating agents and perhaps some other interventions for hypoplastic myelodysplastic syndrome. Of course, we need some drug or intervention for thrombocytopenia. Now that we have more precise molecular tools, there is a question of whether a subset of these patients may be candidates for stem cell transplantation.

 With that, I want to thank you for your attention. Thank you very much.

Source:

Manero G. Resetting Standards in MDS: New Principles for Integrating Innovative Therapy Into Risk-Adapted Decision-Making. Presented at the 2024 Society of Hematologic Oncology meeting. Houston, Texas; September 4-7, 2024.