Decitabine Activity in Chronic Myelomonocytic Leukemia Patients

Abstract

Background: Epigenetic therapy with hypomethylating agents has recently been approved for the treatment of myelodysplastic syndromes (MDS) in Argentina. Chronic Myelomonocytic Leukemia (CMML) is a hybrid disorder characterized by myeloid proliferation and erythroid-megakaryocytic dysplasia. Subgroup analyses (Kantarjian H, Cancer 2006; 106:1794; Steensma DP, ASCO 2008:Abstr7032) and open-label studies (Aribi A, Cancer 2007; 109:713; Wijermans PW, Leuk Res 2008; 32:587) have reported that decitabine (DACOGEN, Janssen Cilag Farmaceutica S.A. and Eisai Inc.) is effective in the management of CMML.Study objective: To compare the clinical and hematological improvement with decitabine among patients with CMML to those with other MDS subtypes.Methods: We enrolled patients with MDS who received decitabine between July 2007 and June 2008 at 17 centers in our country. Inclusion criteria were ≥18 years of age, de novo or secondary MDS and an International Prognosis Scoring System (IPSS) score ≥0.5. Exclusion criteria were diagnosis of acute myeloid leukemia (AML) or other progressive malignant disease. Patients with prior therapy for MDS/CMML were not excluded. Patients were categorized as having CMML or another sub-type of MDS according to FAB/WHO criteria. All pts received decitabine 20 mg/m2 IV over 1 hour once daily for 5 consecutive days repeating every 4 weeks. Overall improvement rate (complete response + marrow complete response + partial response + hematologic improvement) was compared between cohorts with chi-square and Fisher's tests.Results: There were 11 patients with CMML and 27 patients with other subtypes of MDS. Demographic characteristics are summarized in the table. All CMML patients were BCR/ABL negative. Three patients had CMML type II (WHO classification, Blasts ≥10% in marrow and/or ≥5% in peripheral blood) and 8 had CMML type I. Four patients with CMML had proliferative features with WBC >13000/mm3 and splenomegaly at the time of diagnosis. The overall response was 73% in patients with CMML and 33% in patients with other MDS sub-types (p=0.003). Median time to first response in CMML pts was 2 cycles. Tolerability was acceptable in both groups with no significant differences.Conclusion: Although our study group is small, decitabine demonstrated marked activity in CMML. Additional study of decitabine therapy in CMML is warranted.VariableCMML (N=11)Other MDS Subtypes (N=27)Age, Median6767Male, n (%)9 (82%)18 (67%)IPSS Score, n (%)Intermediate-17 (64%)12 (44%)Intermediate-22 (18%)1 (4%)High-Risk2 (18%)14 (52%)No. (%) with Prior Therapy8 (73%)23 (85%)No. of Cycles, Median (Range)4 (2–6)3 (1–8)Treatment Response, n (%)Overall Improvement (CR+PR+mCR+HI)*8 (73%)9 (33%)Complete Response (CR)1 (9%)2 (7%)Partial Response (PR)1 (9%)1 (4%)Marrow Complete Response (mCR)2 (18%)0Hematologic Improvement (HI)4 (36%)6 (22%)Stable Disease (SD)02 (7%)Failure (Progressive Disease or Death)1 (9%)14 (53%)Non-evaluable2 (18%)2 (7%)* (p=0.003)