Improving Quality of Life in LR-MDS Through Anemia Treatment

Christopher Benton, MD

Hematologist/Medical Oncologist

Rocky Mountain Cancer Centers

Aurora, CO

This article is part 1 of a 2-part series from a Case-Based Roundtable event.

CASE SUMMARY

• A 70-year-old man was diagnosed 1 year ago with lower-risk myelodysplastic syndrome (LR-MDS)
  • Multilineage dysplasia
  • Anemia and thrombocytosis (platelets, 500,000/μl)
• SF3B1 mutation negative
• Non-deletion 5q
• No family history of cancer or significant genotoxic agent exposure
• In the last 8 months, he received single-unit packed red blood cell transfusions 3 months apart
• Revised International Prognostic Scoring System: low
• Work-up to assess disease status and response to anemia management:
  • Serum erythropoietin (EPO): 200m U/L
  • RS negative
  • Hemoglobin: 8.3 g/dL
  • White blood cell and absolute neutrophil count: within normal limits
  • Platelets: 450,000/μl

Targeted Oncology: Can you discuss the some of the problems faced by patients with LR-MDS?

Christopher Benton, MD: One of the big issues in these patients is anemia. When you evaluate anemia in these patients, it's always important to remember looking for reversible causes, and so you rule out these reversible causes of anemia. Usually what I do with my patients is, I will periodically check in on these things, because occasionally patients will develop one of these things of the course of treatment. If you rule those things out, and you know that this anemia is due to MDS, I think most of us would check the EPO level and see where that patient stands in terms of EPO.

We have more and more additional therapies that we can use in these lower-risk patients. We oftentimes think of lower risk as patients that we observe. Higher risk is patients that we treat. But in fact, a lot of these lower-risk patients, especially those with anemia, are ones that we want to consider treatment for.

Which treatment options are available in LR-MDS?

One treatment is red blood cell transfusion. There are a lot of challenges inherent in that, in both academics and in community practice. We all think about erythropoiesis-stimulating agents [ESAs]. These are a standard of care that we've been using for a long time, including epoetin alfa and darbepoetin alfa.

More recently, we think about luspatercept [Reblozyl], which is an erythroid maturation agent, or EMA. Even more recently, we're thinking about imetelstat [Rytelo]. Imetelstat is a telomerase inhibitor that's now approved for use for anemia and MDS. We also think about lenalidomide [Revlimid]. Now, lenalidomide is quite effective in anemia, MDS, and deletion 5q [del(5q)] MDS. I think most of my patients who are on lenalidomide with MDS have del(5q), but it can be tried in patients who do not have del(5q) as well. Then there's immunosuppressive therapy with ATG cyclosporine. I think about immunosuppressive therapy for patients with hypoplastic MDS or maybe aplastic anemia.

Finally, what I would refer to as definitive treatment, where you're treating the MDS, and sometimes can see improvement in counts, is with agents like hypomethylation. More recently, we have incorporated targeted therapy. Examples would be ivosidenib [Tibsovo]. This is an IDH1 inhibitor, now approved for use in IDH1-mutated MDS. I have seen some phenomenal responses in patients who are on ivosidenib with an IDH1 mutation. It's a pretty rare mutation, IDH1 and IDH2—probably less than 5% of MDS—but when patients have that, it is definitely an option.

What are some of the treatment goals for this patient population?

For starters, we want to improve the peripheral blood values. I think we all feel better when the hemoglobin is rising. We want to reduce the risk of bleeding and infection. These are problems that patients with MDS can have. In LR-MDS, we want to prevent these kinds of complications, but we also want to decrease the transfusion burden. Transfusions can be a challenge for both providers setting those things up, and especially for patients who have to take a day out of their lives to [get testing] and go to the infusion center and sit there for hours.

Lastly is to improve the quality of life. I think we all want to see a better number. We all want our patients not to need transfusions. But oftentimes, the increase in hemoglobin is concomitant with an increase in quality of life; patients can often feel better when you improve their anemia. It's not a guarantee, though. MDS is an interesting disease to treat, because sometimes you'll improve the hemoglobin, and patients don't have that corresponding increase in their energy level. But if you can keep them out of the transfusion center, that also oftentimes improves their quality of life.

Please discus the long-term goals for patients with MDS.

Ultimately, we want to change the natural progression of the disease. This is something that's especially true in higher-risk MDS. For higher-risk disease, we always think about treatment. Right now, at Rocky Mountain Cancer Centers, we have a very promising trial for high-risk MDS.... We're trying to delay the disease progression. We're trying to improve overall survival. In some patients, we may choose hematopoietic stem cell transplant, which is meant to be curative in these patients with higher-risk MDS.

We also think about in LR-MDS, if we're improving the anemia, we're improving the quality of life, improving their lifestyle, might we be influencing also the longevity and the health of the patient? This may be especially true for patients with, for example, heart disease, where the improvement of anemia might impact not just their quality of life, but also their longevity.

DISCLOSURES: Benton previously reported an advisory board role for Alexion Pharmaceuticals, Inc., Aptitude Health, LLC, Genentech, Inc., GlaxoSmithKline, Novartis Pharmaceuticals Corp., OncoVerity, Inc., and Taiho Oncology, Inc.