Optimizing Outcomes with Azacitidine: Recommendations from Canadian Centres of Excellence

Abstract

Myelodysplastic syndromes (mdss) constitute a heterogeneous group of malignant hematologic disorders characterized by marrow dysplasia, ineffective hematopoiesis, peripheral blood cytopenias, and pronounced risk of progression to acute myeloid leukemia. Azacitidine has emerged as an important treatment option and is recommended by the Canadian Consortium on Evidence-Based Care in mds as a first-line therapy for intermediate-2 and high-risk patients not eligible for allogeneic stem cell transplant; however, practical guidance on how to manage patients through treatment is limited. This best practice guideline provides recommendations by a panel of experts from Canadian centres of excellence on the selection and clinical management of mds patients with azacitidine. Familiarity with the referral process, treatment protocols, dose scheduling, treatment expectations, response monitoring, management of treatment breaks and adverse events, and multidisciplinary strategies for patient support will improve the opportunity for optimizing treatment outcomes with azacitidine.

Therapy with low‐dose azacitidine for MDS in children and young adults: a retrospective analysis of the EWOG‐MDS study group

“…Fifteen episodes of infection were reported for a total of 154 azacitidine cycles (10%), a rate comparable to previous observations for low-dose azanucleoside therapy in children (Phillips et al, 2013). The appropriate judgment of haematological toxicity and consequential dose reduction remains a dilemma in the treatment of disorders whose primary manifestation are cytopenias; current Canadian guidelines for azacitidine in adults with MDS recommend dose reductions only if severe infections occur (Wells et al, 2014).…”

Azacitidine in the ‘real‐world’: an evaluation of 1101 higher‐risk myelodysplastic syndrome/low blast count acute myeloid leukaemia patients in Ontario, Canada

“…A combined analysis of 3 earlier AZA studies by the Cancer and Leukemia Group B demonstrated that 75% of patients achieved a response by 4 cycles of treatment and that 90% of responses were seen by cycle 6 with best response generally occurring 2 cycles past initial response (Silverman et al , ). This is of particular importance, as recommendations suggest continued treatment for 6 months before response evaluation (Buckstein et al , ) and to avoid dose reductions, particularly during the first 6 cycles of treatment (Silverman et al , ; Wells et al , ; NCCN Clinical Practice Guideline in Oncology ).…”

Acute liver failure due to liver parenchymal infiltration with acute myelogenous leukaemia in a patient with myelodysplastic syndrome

“…She was started on Vidaza (azacitidine) 2 weeks after diagnosis, which is a pyrimidine nucleoside analogue of cytidine and indicated as first-line treatment 3. She was admitted for workup of asymptomatic elevation of liver function tests on day 7 of treatment.…”