Effectiveness and Tolerance of Azacitidine for Treating Patients with Chronic Myelomonocytic Leukemia in Community-Based Management.

Azacitidine (AZA) was recently approved in Europe by the EMEA for the treatment of Chronic Myelomonocytic Leukemia (CMMoL). Traditionally, CMMoL has been considered as part of the myelodysplastic syndrome (MDS) according to the FAB (French-American-British) classification. Nowadays, according to the criteria proposed by the World Health Organization (WHO), it is included as a subgroup of diseases of mixed characteristics named as myelodysplastic/myeloproliferative diseases (MDS/MPD) separate from MDS. Recent discoveries in the molecular biology of CMMoL have provided new therapeutic agents to test. Treatment with AZA was approved by the EMEA on the basis of the AZA-001 phase III clinical trial. AZA is also approved for the treatment of the MDS. AZA was available in Spain under compassionate use before its regulatory approval (May 2009). We present the effectiveness and tolerance data for AZA clinical activity in patients with CMMoL included in the Spanish compassionate use registry.

We present the preliminary clinical results taken from data from a longitudinal, multicenter Spanish patient registry, which retrospectively collected data from community-based hematology clinics on the disease course and management of patients with CMMoL treated in a compassionate use setting with AZA, in whom the dosing schedule administered was documented. AZA dosing was applied to the patients in two different dosing schedules in 28-day cycles: either days 1, 2, 3, 4 and 5 or days 1, 2, 3, 4, 5, 8 and 9. Choice of schedule was based on patient status. As of August 1, 2009, data from 10 patients with MDS diagnosed according to the WHO criteria had been collected. Response to treatment was assessed using the International Working Group (IWG 2006) criteria. Treatment toxicity was assessed using the NCI-CTCAE version 3.0 criteria.

Data collection comprised results from 8 male and 2 female, with a median age of 64 years (range 62-80). An intermediate-2/high IPSS risk was documented in 20% of the patients and a 0-1 ECOG status before treatment initiation was documented 80% of the patients. Patients received a median of 5 cycles of AZA (range 2-12). The most frequently used dose was 75 mg/m² (90%). A 5-day dosing schedule was administered to 70% of the patients and a 5+2 day dosing schedule with 2 free days was administered to the remaining 30%. The most frequent administration route was subcutaneous injection (70%). According to the IWG 2006 response criteria, 20% of patients obtained a complete response, 20% achieved a complete bone marrow response, and, in a further 10%, hematological response was documented. The grade 3-4 adverse events, regardless of their relationship with the active treatment, were of hematological nature (neutropenia n=5, thrombocytopenia n=4, anemia n=1). Other grade 3-4 adverse events documented were rash (n=2), injection site reaction (n=1), hypotension (n=1) and constitutional symptoms (n=1). These rates do not differ from those obtained in the AZA-001 study.

These results demonstrate that AZA is effective for the treatment of patients with CMMoL in community-based management. Different dosing schedules are prescribed to patients with CMMoL treated with AZA in the community-based setting. Further analyses from this registry are awaited.

No relevant conflicts of interest to declare.