Guadecitabine in myelodysplastic syndromes: promising but there is still progress to be made
Mené sur 105 patients atteints d'un syndrome myélodysplasique à haut risque ou à risque intermédiaire de récidive, cet essai de phase I/II évalue l'efficacité, du point de vue de la réponse complète, la toxicité et la dose recommandée de la guadécitabine (durée médiane de suivi : 3,2 ans)
Treatment of higher risk myelodysplastic syndromes remains a challenge. Only allogeneic stem-cell transplantation is a potentially curative treatment, but it can only be done in few patients. The hypomethylating agents—azacitidine and decitabine—are generally the first-line treatment for higher risk myelodysplastic syndromes. Some are capable (eg, azacitidine) of substantially improving overall survival. Nevertheless, the 50% response and the median overall survival of about 2 years obtained with azacitidine remain modest. Moreover, survival time of patients with refractory or relapsed disease is very short with a median survival of 4–6 months; no treatment has shown a substantial survival benefit in that disease setting, except allogeneic stem-cell transplantation. To improve survival results with hypomethylating agents in higher risk myelodysplastic syndromes, many cooperative groups have tested new drugs in combination with hypomethylating agents, and some of these drugs have also been tested as single agents after hypomethylating agent failure. Although results of some non-randomised phase 2 studies combining hypomethylating agents with another drug (eg, histone deacetylase inhibitors, lenalidomide, idarubicin, and rigosertib among others) have shown a promising proportion of patients achieving responses, no randomised trial has so far shown any significant response or survival benefit of such combinations over hypomethylating agents alone for first line treatment. Similarly, for patients for whom hypomethylating agents are not successful, only rigosertib has shown a modest, non-significant, survival advantage in patients with primary resistance to hypomethylating agents.
The Lancet Haematology , commentaire, 2018