Decitabine Activity in Chronic Myelomonocytic Leukemia Patients
Authors: Iastrebner Marcelo , Garay Guy , Klein Graciela , Flores Alejandro , Nucifora Elsa , Alfonso Graciela , Diego Moro , Basquiera Ana , Goalons Moira Lluesma , Saracut Diana , Gonzalez Miguel , Quiroga Luis , Palmer Luis , Santini Fernando 
Published: April 2020

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, Cancer2006;106:1794; Steensma DP, ASCO2008:Abstr7032) and open-label studies (Aribi A, Cancer2007;109:713; Wijermans PW, Leuk Res2008;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 &gt;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.
Variable CMML (N=11) Other MDS Subtypes (N=27) * (p=0.003) Age, Median 67 67 Male, n (%) 9 (82%) 18 (67%) IPSS Score, n (%) Intermediate-1 7 (64%) 12 (44%) Intermediate-2 2 (18%) 1 (4%) High-Risk 2 (18%) 14 (52%) No. (%) with Prior Therapy 8 (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%) 0 Hematologic Improvement (HI) 4 (36%) 6 (22%) Stable Disease (SD) 0 2 (7%) Failure (Progressive Disease or Death) 1 (9%) 14 (53%) Non-evaluable 2 (18%) 2 (7%)