Examining azacitidine-based treatment approaches

This study examined 3 different azacitidine-based (Vidaza) treatment approaches for patients with chronic myelomonocytic leukemia (CMML). Researchers reported that patients with CMML showed better treatment response when azacitidine was combined with lenalidomide (Revlimid).

Myelodysplastic syndromes (MDS) are a group of cancers in which the bone marrow makes too many immature blood cells. Some types of MDS can develop into acute or chronic myelomonocytic leukemia. The hypomethylating agent azacitidine has been approved for the treatment of MDS. Azacitidine works by inhibiting a process called DNA methylation, which is essential for cell reproduction. Because the abnormal cells cannot divide and grow, they die. Azacitidine can be administered on its own or combined with the immunotherapy lenalidomide (Revlimid) or with the T-cell lymphoma therapy vorinostat (Zolinza). Which treatment strategy is most suitable for high-risk MDS and CMML patients has not been fully studied.

277 high-risk MDS and CMML patients were randomly assigned to treatment groups. 92 received azacitidine alone. 93 were treated with azacitidine plus lenalidomide. 92 patients received azacitidine plus vorinostat. Patients were followed for an average of 23 months.

The overall response rate was similar across the 3 treatment groups. It was 38% for patients receiving azacitidine, 49% for azacitidine plus lenalidomide, and 27% for azacitidine plus vorinostat. However, for patients with CMML the overall response rate was significantly higher for azacitidine plus lenalidomide (68%) compared to azacitidine alone (28%).

Average overall survival (time from treatment until death from any cause) was 17 months. It did not differ significantly across the 3 treatment groups (the range was 15 to 19 months). Overall survival was poorer for patients considered high-risk due to genetic abnormalities (making CMML harder to treat). Overall response rates were also lower for patients with genetic abnormalities.

Patients in the azacitidine plus vorinostat group showed more serious side effects related to the stomach and intestines. Patients treated with azacitidine plus lenalidomide arm were more likely to present with a serious rash. Other side effects were similar across treatment groups. The most common serious side effect was low neutrophil levels (a type of white blood cell) with a fever. It was observed in 89 to 91% of patients.

Researchers concluded that azacitidine-based combinations were not superior to azacitidine alone in the entire patient group. However, patients with CMML showed better treatment response when azacitidine was combined with lenalidomide.

Azacitidine is not typically a first-line treatment for CMML.