Activity of Azacitidine (AZA) in Chronic Myelomonocytic Leukemeia (CMML)

Background: CMML is a distinct clinicopathologic entity recognized by the World Health Organization (WHO). Treatment of CMML by AZA was approved by the US Food and Drug Administration on the basis of a phase III randomized trial conducted by the Cancer and Leukemia Group B, for the treatment of myelodysplastic syndromes (MDS). Only 14 patients with CMML were included in the pivotal trial.

Methods: We retrospectively reviewed our institutional experience of CMML treatment with AZA. 39 patients were treated between May 1996 and January 2006. AZA was given at 75 mg/m² subcutaneously daily for seven days every 4 weeks or 100 mg/m² daily for 5 days every 4 weeks. Patients who received at least 2 cycles of therapy were considered evaluable for response (N=34). All patients were evaluated for toxicity. The modified International Working Group standardized response criteria for MDS were used for evaluation. The response to AZA, duration of response, tolerability and survival are presented.

Results: Patients had a median age of 68.5 years (range: 46–83); male: female ratio was 4.5:1. 28 patients (72%) had a WBC >12,000/μl (myeloproliferative form of CMML). 6 patients had 20–30% blasts in their bone marrow. The International Prognostic Scores were as follows: Low (N=3), Intermediate-1 (N=13), Internediate-2 (N=14), High (N=7), unknown in 2 patients (due to lack of aspirate particles in one and cytogenetics in the other). CMML was secondary to chemotherapy/radiotherapy in 5 patients. Overall response was seen in 14 patients (41%): 5 patients (15%) had a complete response (CR), 9 patients (26%) had hematologic improvement. Mean duration of response was 16.2 months (range: 3–50+); 2 patients are still alive and being treated with CR for >50 months. Average number of cycles to respond was 2.4 cycles (range: 1–6). Splenomegaly was present in 8 patients (20%). Treatment resulted in normalization of spleen size in 1 patient, decrease in 3 patients and no effect in 4 patients. Mean overall survival was 13.2 months (range 1–72). Average survival in responders was 23.5 months (5–72) while average survival in non-responders was 7.48 months (<1–23). Treatment was well tolerated. The most common non-hematological toxicities were nausea and fever.

Conclusions: AZA appears to be effective and well tolerated in CMML.