What are the treatment options for Chronic Myelomonocytic Leukemia (CMML)?

From the Guidelines

The treatment for Chronic Myelomonocytic Leukemia (CMML) should be guided by the patient's symptoms, disease risk, and overall health status, with a focus on improving morbidity, mortality, and quality of life, as recommended by the most recent study 1.

Treatment Approach

The approach to treating CMML depends on whether the disease presents with myelodysplastic (MD) or myeloproliferative (MP) features, as well as the number of blasts in the bone marrow.

• For patients with MD-CMML and less than 10% blasts in the bone marrow, supportive therapy aimed at correcting cytopenias is recommended, with the use of erythropoietic stimulating agents for severe anemia 1.
• For those with MD-CMML and a high number of blasts (≥10% in bone marrow), supportive therapy should be integrated with hypomethylating agents like 5-azacytidine or decitabine 1.
• Patients with MP-CMML and a low number of blasts should be treated with cytoreductive therapy, with hydroxyurea being the drug of choice to control cell proliferation and reduce organomegaly 1.
• For MP-CMML with a high number of blasts, blastolytic therapy with polychemotherapy followed by allogeneic stem cell transplantation (allo-SCT) is recommended, if possible 1.

Allogeneic Stem Cell Transplantation

Allo-SCT is considered the only potentially curative option for CMML, particularly for eligible younger patients with higher-risk disease.

• The decision to proceed with allo-SCT should be based on the patient's overall health status, disease risk, and the presence of comorbidities, as outlined in the recent recommendations from the EBMT PH&G Committee 1.
• Upfront transplantation without prior disease-modifying treatment is preferred to maximize the chances of reaching allo-HCT, irrespective of bone marrow blast counts 1.

Monitoring and Adjustments

Regular monitoring of blood counts and bone marrow evaluations is essential throughout treatment to assess response and adjust therapy as needed.

• This approach allows for the optimization of treatment strategies to improve patient outcomes in terms of morbidity, mortality, and quality of life.

From the FDA Drug Label

The overall response rate (CR + PR) of 15.7% in azacitidine for injection-treated patients without AML (16. 2% for all azacitidine for injection randomized patients including AML) was statistically significantly higher than the response rate of 0% in the observation group (p<0. 0001) Response occurred in all MDS subtypes as well as in patients with adjudicated baseline diagnosis of AML. Study 2, a multi-center, open-label, single-arm study of 72 patients with RAEB, RAEB-T, CMMoL, or AML was also carried out. Treatment with subcutaneous azacitidine for injection resulted in a response rate (CR + PR) of 13. 9%, using criteria similar to those described above.

Cmml2 treatment with azacitidine for injection resulted in a response rate of 13.9% in Study 2.

• The response rate was statistically significantly higher than the response rate of 0% in the observation group.
• Key benefits of azacitidine for injection treatment include:
  • Decrease in bone marrow blasts percentage
  • Increase in platelets, hemoglobin or WBC
  • Transfusion independence during PR or CR
• The median duration of clinical response of PR or better was estimated as 430 days in Study 2 2.

From the Research

Cmml2 Treatment Overview

• Cmml2, or chronic myelomonocytic leukemia, is a type of cancer that affects the blood and bone marrow.
• Treatment options for Cmml2 are limited, but hypomethylating agents such as azacitidine and decitabine are commonly used 3, 4, 5.
• These agents have been shown to improve overall response rates and complete remission rates in patients with Cmml2, although the responses are often transient 3, 4, 5.

Azacitidine Treatment

• Azacitidine has been shown to be effective in the treatment of Cmml2, with an overall response rate of 39% and a complete response rate of 11% 3.
• The median overall survival for patients treated with azacitidine was 12 months, with a statistically significant overall survival advantage in responders compared to nonresponders 3.
• Azacitidine has also been compared to decitabine in the treatment of Cmml2, with decitabine showing a higher complete remission rate, but also a higher risk of grade 3/4 cytopenia 6.

Emerging Treatments

• Several emerging treatments are being investigated for the treatment of Cmml2, including small molecule inhibitors, immune therapies, and monoclonal antibodies 7.
• These treatments target specific molecular mechanisms involved in the pathogenesis of Cmml2, such as IDH, FLT3, MEK/ERK, PLK1, and splicing inhibitors 7.
• Further research is needed to determine the efficacy and safety of these emerging treatments in patients with Cmml2 7.

Risk Stratification and Management

• Risk stratification is important in the management of Cmml2, with several molecularly integrated prognostic models available, including the Groupe Français des Myélodysplasies (GFM), Mayo Molecular Model (MMM), and the CMML specific prognostic model (CPSS-Mol) 5.
• These models incorporate various risk factors, including genetic mutations, absolute monocyte count, hemoglobin level, platelet count, and the presence of circulating immature myeloid cells 5.
• Allogeneic stem cell transplant is the only potentially curative option for Cmml2, but is associated with significant morbidity and mortality 5.