Oral Decitabine-Cedazuridine Is a Game Changer for MDS and CMML Treatment

James K. McCloskey II, MD

For patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML), the advent of oral decitabine-cedazuridine (Inqovi) represents a significant advancement in treatment. This oral formulation provides a bioequivalent and far more convenient alternative to intravenous (IV) decitabine (Dacogen), empowering patients to maintain their quality of life while receiving effective therapy in the comfort of their home.

As a physician dedicated to helping patients live longer and better, I’ve witnessed firsthand the burden that frequent hospital visits for IV infusions place on patients battling these diseases. Although oral decitabine-cedazuridine may appear simply as a biosimilar on paper, its impact on a patient’s daily life is transformative.

Long-term data from the phase 3 ASCERTAIN trial (NCT03306264), recently published in The Lancet Haematology, confirm the safety and efficacy of this oral formulation.1 The study demonstrated that the toxicities observed with oral decitabine-cedazuridine are consistent with those of IV decitabine. Critically, the primary end point of total drug exposure was met, with the oral formulation achieving 98.93% (90% CI, 92.66%-105.60%) of the IV decitabine exposure, establishing pharmacokinetic equivalence.

This equivalence translates to real-world benefits for patients. For example, one of my patients participated in ASCERTAIN for over 2.5 years. Imagine the cumulative time this individual would have spent in a clinic chair receiving IV infusions, time that was reclaimed thanks to the oral formulation.

Although the benefits are clear, some considerations warrant attention. Patients with compromised gastrointestinal absorption, such as those who have undergone gastric bypass surgery, may not be ideal candidates for oral decitabine-cedazuridine. Close monitoring is also essential, particularly during the initial treatment cycles.

The availability of oral decitabine-cedazuridine has already shifted the treatment paradigm for patients with MDS and CMML. Many of my patients have transitioned from IV to oral therapy, experiencing improved convenience without compromising efficacy. Furthermore, this oral formulation has opened doors for novel combination strategies. The National Comprehensive Cancer Network guidelines now recognize oral decitabine-cedazuridine as a potential partner for venetoclax (Venclexta) in patients with higher-risk MDS or acute myeloid leukemia.

The success of oral decitabine/ cedazuridine has spurred further research in this area. A phase 2/3 study (NCT04256317) evaluating oral azacitidine (Vidaza) in combination with cedazuridine recently completed its phase 2 portion, and we eagerly await results from the expansion cohort. This is just the beginning of the story of oral hypomethylating agents.

Recent challenges in drug development for high-risk MDS highlight the critical importance of continued clinical trial enrollment. Collaboration among academic and community oncologists is crucial to advancing research and providing patients access to promising new therapies. At Hackensack Meridian Health, we are committed to fostering these partnerships to improve outcomes for all patients.

Reference

1. Garcia-Manero G, McCloskey J, Griffiths EA, et al. Oral decitabine-cedazuridine vs intravenous decitabine for myelodysplastic syndromes and chronic myelomonocytic leukaemia (ASCERTAIN): a registrational, randomised, crossover, pharmacokinetics, phase 3 study. Lancet Haematol. 2024;11(1):e15-e26. doi:10.1016/S2352-3026(23)00338-1