BSH 2022 | Diagnosis and management of CMML

CMML stands for chronic myelomonocytic leukemia. It’s one of the MDS or myelodysplastic/myeloproliferative overlap syndromes. So its diagnosis relies on the presence of both dysplasia, resulting in bone marrow failure and cytopenias, but at the same time, leukocytosis and myeloproliferation, particularly involving the monocyte lineage. So for the diagnostic criteria, you need to have both evidence of dysplasia in the bone marrow, but also a monocytosis of greater than one times 10⁹ per liter. And that has to be more than 10% of the total white count. Increasingly, as we learn more about the molecular makeup, the presence of mutations is helping to establish the diagnosis in more challenging cases. There are some very characteristic mutations and combinations of mutations. And I think in the future, it’s likely we’ll be moving more towards a molecular or an integrated molecular classification.

When it comes to management, I think CMML treatment has been somewhat neglected over the years. There’s very few treatment options available. Currently, there’s only three FDA-approved drugs. The principles of management are really to divide patients according to risk status. There are many prognostic scoring tools available for lower-risk patients. The treatment is largely supportive. Many patients are managed by active surveillance only, sometimes there’s a role for erythroid stimulating agents if the anemia is a dominating feature. For the higher-risk patients and higher-risk will be due to the presence of certain mutations, higher blast counts, also a more proliferative disease. For higher-risk patients, most would benefit from disease modifying treatments. Five to 10% of patients will be young and fit enough to have an allogeneic transplant. And that is the only potential cure for this disease. But as I say, most patients aren’t eligible for that.

In terms of disease modifying therapy, it’s best to think of it in terms of the dominant clinical feature. Patients who have a dominant proliferative picture and benefit from cytoreduction. Nothing at the moment has been proven any better than hydroxycarbamide. So, that’s still the standard of care in most countries. We do now have hypomethylating agents. So azacitidine, decitabine in the UK. Only azacitidine is approved, and it’s approved for patients with a blast count above 10% and without a myeloproliferative picture. So a white count less than 13. So for that group of patients, azacitidine is likely beneficial, but we definitely need better treatments going forward.