Decitabine in myelodysplastic syndromes and chronic myelomonocytic leukemia: Argentinian/South Korean multi-institutional clinical experience

Abstract

This multicenter, open-label study evaluated the efficacy and safety of decitabine in patients from Argentina and South Korea with myelodysplastic syndromes or chronic myelomonocytic leukemia. Of 106 patients who received decitabine 20 mg/m(2) intravenously over 1 h once daily for 5 days in 4-week cycles, 99 patients were evaluable after receiving at least two cycles. The overall improvement rate was 35% (19% complete response +4% marrow complete response +4% partial response +8% hematologic improvement). Overall survival at 2 years was 71%. Treatment-related adverse events included febrile neutropenia, thrombocytopenia and bleeding, asthenia, fatigue, and eosinophilia. After complete response (CR), three patients received an allogeneic stem cell transplant. Four patients who relapsed after CR responded to decitabine retreatment. Acute myelogenous leukemia developed during follow-up in 21% of patients. Decitabine in a 5-day outpatient administration schedule was effective and well tolerated in typical clinical practice settings in South America and Asia.

Clinical development of demethylating agents in hematology

“…In an update of the study, Kantarjian and colleagues reported an overall improvement rate of 70% (24). Steensma and colleagues and investigators in Argentina and South Korea investigated the same dose and schedule as the study above and demonstrated 32% and 35% ORRs, respectively (25,26).…”

A phase 2 trial of combination therapy with thalidomide, arsenic trioxide, dexamethasone, and ascorbic acid (TADA) in patients with overlap myelodysplastic/myeloproliferative neoplasms (MDS/MPN) or primary myelofibrosis (PMF)

“…The treatment results did not differ significantly between untreated and previously treated individuals, emphasizing the benefit of combination therapy at any stage of disease. With the current availability of newer agents, such as hypomethylators, immunomodulatory derivatives, and JAK2 inhibitors, further opportunities will emerge for new combination therapies, some of which already have demonstrated promising clinical efficacy 28, 30, 38. One next, obvious step would be to substitute lenalidomide or pomolidomide for thalidomide in the current study design.…”

“…Allogeneic stem cell transplantation is the only potential curative modality, yet most patients are not suitable candidates. Alternatives are used either to treat symptoms or to attempt to treat the disease, largely by cross‐applying therapeutic principles from MDS therapies: response rates, however, usually are <20% to 25% and are of short duration 20‐39. Thalidomide and its successor lenalidomide are antiangiogenesis agents with cytokine‐modulating activity that have been used in combination with steroids in PMF patients and produce response rates from 40% to 50% 23, 24.…”

Epigenetic Therapy of Cancer

“…An international, multicenter, nonrandomized, and open-label study from Argentina and South Korea treated 106 MDS and CMML patients using the same treatment schedule as the ADOPT trial (Iastrebner et al 2010 ). The overall improvement rate of 99 assessable patients was 35 % (19 % CR + 4 % mCR + 4 % PR + 8 % HI).…”