Is there a path forward for immunotherapy in patients with myelodysplastic syndromes?
Mené sur 127 patients atteints d'un syndrome myélodysplasique à haut risque d'évolution (âge médian : 73 ans), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse complète et de la survie sans progression, et la toxicité de l'ajout de sabatolimab (un anticorps ciblant TIM-3) à un agent hypométhylant en traitement de première ligne
Immunotherapy in some forms is a well established treatment in patients with myelodysplastic syndromes. Allogeneic haematopoietic stem-cell transplantation (HSCT) has long been an efficacious treatment for high-risk myelodysplastic syndromes, and it is the only option that allows durable disease control and a potential cure for some patients. 1 However, allogeneic HSCT is not suitable for many patients due to frailty or comorbidities. For these patients, the enduring standard of care therapy is treatment with a hypomethylating agent. In the AZA-001 trial, 2 patients with higher-risk myelodysplastic syndromes given the hypomethylating agent azacitidine had median overall survival of 24·5 months. However, the overall survival with azacitidine monotherapy in the AZA-001 trial might have been overestimated, because in multiple real-world analyses of azacitidine in patients with higher-risk myelodysplastic syndromes, median overall survival ranged between 12 months and 18 months. 3 Additionally, overall survival estimates after treatment failure of hypomethylating agents is short (5·6 months), and no therapies are approved in this setting. 4 Therefore, there is an urgent unmet clinical need to develop novel therapies, hypomethylating agent-based combinations or otherwise, to improve outcomes in the front-line management of myelodysplastic syndromes. To date, no improvements in outcomes have been observed in randomised trials combining hypomethylating agents with targeted therapies, such as the histone deacetylase inhibitor vorinostat, the NEDD8 inhibitor pevonedistat, and the TP53 refolding agent APR-246, when compared with hypomethylating agents alone. 5 The remaining accruing phase 3 trials in high-risk myelodysplastic syndromes include the VERONA trial (NCT04401748) comparing venetoclax in combination with a hypomethylating agent with a hypomethylating agent alone and the SELECT-MDS-1 trial (NCT04797780) of tamibarotene, an oral selective retinoic acid receptor
α agonist, with the same design.