Venetoclax with HMAs for CMML Study Results

Combining venetoclax (VEN) with hypomethylating agents (HMAs) can improve response rates for patients with chronic myelomonocytic leukemia (CMML), but it does not improve survival. A multicenter analysis found that adding venetoclax to hypomethylating agents therapy improved response rates, including overall response rate (ORR) and complete remission (CR), but not overall survival.

Hypomethylating agents (HMAs) are the only approved therapy for CMML. Venetoclax has been added to HMAs to improve response rates and survival. HMAs are not known to prolong overall survival (OS) or stop the disease from progressing. Based on data from AML and MDS, venetoclax  has been combined with HMAs to try to improve response rates.

What Is Venetoclax?

Venetoclax (Venclexta) is a targeted therapy known as a BCL-2 inhibitor. In certain types of cancer, there is an overproduction of a protein called BCL-2. This protein helps cancer cells survive by blocking programmed cell death. By attaching to the BCL-2 protein, venetoclax prevents it from doing its job, allowing cancer cells to undergo apoptosis as they normally would. This leads to the death of cancer cells and may make them more sensitive to other anti-cancer treatments. Venetoclax can work relatively quickly, with many patients seeing a reduction in disease burden within about one month of starting therapy.

Some of the possible side effects of venetoclax are: low white blood cell/red blood cell/platelet counts, nausea, diarrhea, fatigue, anemia and cough. It can cause serious side effects, such as tumor lysis syndrome and infections.

Combining Venetoclax with HMAs

In a multicenter analysis presented at the 66th annual American Society of Hematology (ASH), patients were given HMAs alone and also in combination with venetoclax. The median age of patients was 71 years old. 89 patients were treated. The hypomethylating agents used were azacitidine with decitabine.

• The overall survival (OS) of patients was 25.1 months.
• Overall response rate (ORR) for HMAs alone was 46% and 95% for those treated with venetoclax + HMAs combination.
• A total of 29 patients went on to receive allogeneic stem cell transplant (alloSCT).
• There was no significant overall survival difference between the HMA+ venetoclax combination versus HMAs alone (19.1 months versus 19.1 months).

Conclusion

Chronic myelomonocytic leukemia (CMML) is a rare blood cancer, most commonly diagnosed in older adults—typically between the ages of 73 and 75—and more often in men. In this study, most participants were considered high-risk. While combining venetoclax with hypomethylating agents (HMAs) led to higher response rates compared to HMAs alone, it did not result in longer overall survival. These findings highlight the need for continued research to discover more effective treatment options.

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Source:

• Venetoclax (VEN) Improves Response Rates but Not Survival in Patients with Chronic Myelomonocytic Leukemia (CMML) Treated with Hypomethylating Agents (HMA): A Multicenter, Propensity Score Analysis