A multi-centre phase 2 study of azacitidine in chronic myelomonocytic leukaemia

Drummond, M. W.; Pocock, Christopher; Boissinot, Marjorie; Mills, Juliet; Brown, Julia; Cauchy, Pierre; Cross, Nicholas C. P.; Hartley, Suzanne; Kell, Jonathan; Szubert, Alex J.; Cockerill, Peter N.; Bowen, D.

doi:10.1038/leu.2014.85

Cited by 35 publications

(39 citation statements)

References 12 publications

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“…Previous small case series have described efficacy in this disorder (Costa et al , ; Breccia et al , ; Thorpe et al , ). However a recent multicentre Phase 2 trial by the UK NCRN (National Institute for Health Research [NIHR] Cancer Research Network) MDS Trial Subgroup demonstrated limited activity but with a small number of clinically meaningful responses (Drummond et al , ). Decitabine also has reported efficacy in CMML but remains unlicensed by the EMEA (Aribi et al , ; Kantarjian et al , ; Oki et al , ; Wijermans et al , ; Braun et al , ).…”

Section: Management Of Mdsmentioning

confidence: 99%

“…A recent French study demonstrated a 38% response rate in a high-risk CMML population, including 10% complete response and 21% bone marrow response (Braun et al, 2011). 75% patients on hydroxycarbamide were able to stop this treatment, a similar proportion to that in the UK trial of azacitidine (Drummond et al, 2012). The role of hypomethylating agents has not been definitively established in all CMML patients and azacitidine can only be recommended for use within the licensed indication or in clinical trials.…”

Section: Management Of Cmmlmentioning

confidence: 99%

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Guidelines for the diagnosis and management of adult myelodysplastic syndromes

et al. 2013

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Section: Management Of Mdsmentioning

confidence: 99%

Section: Management Of Cmmlmentioning

confidence: 99%

Guidelines for the diagnosis and management of adult myelodysplastic syndromes

et al. 2013

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“…Median overall survival ranged between 12 and 37 months. 106,[110][111][112] AZA is licensed for nonproliferative CMML-2 in many countries; DAC is licensed in the United States only. These drugs are globally well tolerated, with myelosuppression being the major toxicity.…”

Section: Hmasmentioning

confidence: 99%

How I treat chronic myelomonocytic leukemia

Solary

Itzykson

2017

Blood

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Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy that may deserve specific management. Defined by a persistent peripheral blood monocytosis ≥1 × 109/L and monocytes accounting for ≥10% of the white blood cells, this aging-associated disease combines cell proliferation as a consequence of myeloid progenitor hypersensitivity to granulocyte-macrophage colony-stimulating factor with myeloid cell dysplasia and ineffective hematopoiesis. The only curative option for CMML remains allogeneic stem cell transplantation. When transplantation is excluded, CMML is stratified into myelodysplastic (white blood cell count <13 × 109/L) and proliferative (white blood cell count ≥13 × 109/L) CMML. In the absence of poor prognostic factors, the management of myelodysplastic CMML is largely inspired from myelodysplastic syndromes, relying on erythropoiesis-stimulating agents to cope with anemia, and careful monitoring and supportive care, whereas the management of proliferative CMML usually relies on cytoreductive agents such as hydroxyurea, although ongoing studies will help delineate the role of hypomethylating agents in this patient population. In the presence of excessive blasts and other poor prognostic factors, hypomethylating agents are the preferred option, even though their impact on leukemic transformation and survival has not been proved. The therapeutic choice is illustrated by 4 clinical situations among the most commonly seen. Although current therapeutic options can improve patient’s quality of life, they barely modify disease evolution. Improved understanding of CMML pathophysiology will hopefully lead to the exploration of novel targets that potentially would be curative.

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“…Cytoreductive therapy, including intensive chemotherapy, has been reported to be disappointing in patients with CMML owing to its poor response rate and significant toxicity [5][6][7]. Recent studies have shown that DNA hypomethylating agents, such as 5-azacitidine and decitabine, are well tolerated and associated with a significant response rate [8][9][10][11]. The main aim of these treatments is to improve symptoms and control the proliferation of leukemic cells, not to provide long-term remission in patients with CMML.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Impact of Donor Source on Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in Adults with Chronic Myelomonocytic Leukemia: A Nationwide Retrospective Analysis in Japan

Itonaga

Aoki

et al. 2018

Biology of Blood and Marrow Transplantation

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapeutic option for patients with chronic myelomonocytic leukemia (CMML). We retrospectively compared the post-transplantation outcomes of 159 patients with CMML who underwent allo-HSCT using 4 types of donor sources: HLA-matched related donor graft, unrelated bone marrow (U-BM), unrelated cord blood (U-CB), and HLA-mismatched related donor graft. The median patient age at allo-HSCT was 54 years (range, 16 to 75 years). In multivariate analyses, the use of HLA-matched related donor grafts correlated with better overall survival than U-BM (hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.21 to 3.48; P = .008), U-CB (HR, 3.80; 95% CI, 2.07 to 6.95; P < .001), or HLA-mismatched related donor grafts (HR, 6.18; 95% CI, 2.70 to 14.15; P < .001). Mortality after the relapse or progression of CMML did not significantly differ among the 4 types of donor source. Transplantation-related mortality was highest in recipients of U-CB (HR, 3.32; 95% CI, 1.33 to 8.26; P = .010). In patients with CMML, allo-HSCT using an alternative donor may contribute to durable remission; however, further improvements in transplantation-related mortality are required for this type of transplantation.

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A multi-centre phase 2 study of azacitidine in chronic myelomonocytic leukaemia

Cited by 35 publications

References 12 publications

Guidelines for the diagnosis and management of adult myelodysplastic syndromes

Guidelines for the diagnosis and management of adult myelodysplastic syndromes

How I treat chronic myelomonocytic leukemia

Prognostic Impact of Donor Source on Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in Adults with Chronic Myelomonocytic Leukemia: A Nationwide Retrospective Analysis in Japan

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