Overall survival among patients with myelodysplastic syndromes (MDS) and neoplasms may be impacted greater by time to allogeneic stem cell transplantation (alloHCT) than by treatment response to hypomethylating agent (HMA)-based therapy, according to a retrospective study on data from the VALIDATE database.

These results were presented by Benjamin Rolles, MD, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, at the 66^th ASH Annual Meeting in San Diego, California.

Recent clinical response criteria, including International Working Group (IWG) 2023 and International Prognostic Scoring System-Molecular (IPSS-M), have been published and used to assess the efficacy of HMA-based therapy for patients with MDS and neoplasms. Researchers sought to determine the impact of IWG 2023 response criteria on overall survival (OS) among patients undergoing alloHCT and those who did not receive a transplant as well as determining optimal time-to-transplant.

“Baseline IPSS-M risk and alloHCT had an independent impact on OS, while IWG 2023 defined cCR [composite complete response] had an independent effect on OS only in non-transplanted MDS patients,” Rolles and colleagues concluded, adding, “while this retrospective analysis occurred at large academic centers with specific expertise in the management of MDS, our data may have an impact on clinical practice.”

Transcript:

Good morning. My name is Benjamin Rolles. I'm an MD and research fellow at the Brigham and Women's Hospital and the Dana-Farber Cancer Institute. I'm very excited that I have an oral talk here at the ASH meeting about new insights in MDS.

I'm representing the VALIDATE study. It's a huge database out of 30 different cancer centers worldwide, all managed by the Yale Cancer Center. We are especially looking on the interplay between treatment response based on molecular risk transplant and time to transplant. A little bit about the backgrounds: MDS still has a poor outcome, especially with higher risk patients. A recent paper has shown that, especially in higher-risk patients, the time to transplant matters a lot. And there's a high need for new treatment therapies and how to find out which patient benefit from a therapy and which patient does not benefit.

Because of that, we focused on treatment response depending on different factors. We checked, does treatment response matter in the context with transplantation or without transplantation? Our major finding was that of course, as we expected, treatment response matters in non-transplant patients. But interestingly, we found, at least in our database, that when patients had undergone transplant, that the treatment response was not as relevant as we expected.

Due to that fact, we also looked on the time to transplant. Even in patients who responded to therapy before transplantation, we found out that still in these patients, the time-to-transplant was a very important factor.

What does it mean? First of all, I have to say that our database is a retrospective study. There are a lot of limitations, so we cannot draw clear conclusions in the sense of we used buckets of response, so we didn't check really for blast counts. That's something what we are still doing. But we checked for a composite complete response or a no composite complete response, meaning did patients have a blast clearance or no blast clearance? And we also hadn't any randomization. It's really hard to draw a clear conclusion.

But we assume, at least based on our data, that there are some patients, especially higher-risk MDS patients, where maybe the treatment response is not as important as we think, especially when these patients go to transplant. So, it's maybe more important getting certain patients faster to the stem cell transplantation and don't maybe waste time waiting for a response. That's at least what our data suggests, but we still have to work on that in more detail.

Source:

Rolles B, Bewersdorf J, Kewan T, et al. Impact of response to hypomethylating agent-based therapy on survival outcomes in the context of baseline clinical-molecular risk and transplant status in patients with myelodysplastic syndromes/neoplasms (MDS): an analysis from the International Consortium for MDS (icMDS) Validate database. Dec 7-10, 2024; San Diego, CA. Abstract: 664