Exploring Diagnostic Criteria and Treatment Options for Patients With CMML

At the 2024 Lymphoma, Leukemia & Myeloma Congress in New York, New York, Mrinal Patnaik, MD, Mayo Clinic, Rochester, Minnesota, discusses the diagnostic criteria and expanding treatment options for patients with chronic myelomonocytic leukemia (CMML).

“At [the] Mayo Clinic, we've been working hard on developing clinical trials, exploiting unique therapeutic vulnerabilities based on biology of the disease. With that, we hope that we can advance cures,” concluded Dr Patnaik.

Transcript:

Good afternoon, everyone. My name is Dr. Mrinal Patnaik and I'm a professor of hematology at the Mayo Clinic in Minnesota. I'm here today at the 2024 Lymphoma, Leukemia, and Myeloma Congress in New York City.

I'm going to be summarizing CMML today. This is a hematological malignancy that is becoming increasingly prevalent because of better diagnostic criteria, and it's important for providers to understand the nuances associated with this disease. CMML typically presents in the seventh decade of life. Patients can get symptomatic because their spleen increases, they have drenching night sweats, and then eventually there's a bone marrow failure where they need blood transfusions, and sometimes platelet transfusions.

About a third of these patients will transform into a more aggressive hematological malignancy called acute myeloid leukemia (AML). In those instances, the survival rates are not good. The key here is to identify patients early, risk stratify them appropriately, and offer them therapies when needed.

In patients who are appropriate for stem cell transplantation, [we] get them to a transplant center where the only potentially curative modality really is transplant. That's how we approach these patients. In terms of risk stratification, there are several clinical variables that play an important role [such as] degree of elevation in white blood cell count, monocyte count blast, low platelets, [and] anemia.

There is 1 molecular abnormality. It's a gene called ASXL1, which is now present in most of the next generation sequencing panels. When that gene is mutant, it is associated with more aggressive subtypes of CMML. These patients tend to progress quicker to AML, and they also have shorter overall survival [rates]. For the providers out there, anytime you see a patient presenting with sustained monocytosis where the monocyte count is greater than 500 [and] has been going on for more than 3 months [and there is] the absence of other causes, it's important to evaluate them for CMML.

Once you make a diagnosis of CMML, the next question the patient's going to ask is: “What are my outcomes like?” That's where the risk stratification comes into play. There are 3 or 4 molecular models that are available where you can access the patient's data and input that into the model, and that gives you a rough estimate of outcomes over the next 5 years. Broadly, all these models will divide patients into higher risk and lower risk. The lower-risk patients are expectantly managed, where you wait and watch, you treat symptoms, you help palliate their lives so that they live their lives with dignity. But [with] the higher-risk patients, if they are age appropriate, do not have significant comorbidities, [then] these are patients [where] transplant plays a role.

To get patients to transplant, sometimes you may need bridging therapy. These are treatment options that are given so that you could either reduce the blast or keep the disease under control until they can get to transplant. There is a lot happening in this space. Why? Because what exists is not good enough. Drugs like decitabine and azacitidine have been FDA-approved since 2004 onwards. They work to some extent, but they don't cure the disease. In patients with proliferative CMML, they are quite ineffective in many instances.

At [the] Mayo Clinic, we've been working hard on developing clinical trials, exploiting unique therapeutic vulnerabilities based on biology of the disease. With that, we hope that we can advance cures. The goal is not to make the cure of disease more grievous than the endurance [of it], to enable patients to live with dignity. And if we can't do that, palliate symptoms so that they can die with dignity. Thank you.

Source:

Patnaik M. Classification and Treatment of Chronic Myelomonocytic Leukemia. Presented at Lymphoma, Leukemia & Myeloma Congress; October 16-19, 2024. New York, NY.